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2 0 2 0 HEALTH RESEARCH PROJECTS
Table of Contents Biomedical Engineering Vibhudutta Awasti University of Oklahoma Health Sciences Center 7 A new polymer to modify nanoparticles and suppress toxic immune reactions Aurelie Azoug Oklahoma State University 8 A smart skin to prevent bed sores Yu Feng Oklahoma State University 9 Understanding the effects of sphero cylinder drug particle shape to enhance small airway drug delivery for better emphysema treatment outcomes Ashley Ford Versypt Oklahoma State University 10 Determining how diabetic kidney disease starts Roger Harrison University of Oklahoma 11 Novel targeted protein drug conjugates for treating metastatic breast cancer combined with immunostimulation and mTOR inhibition Michael Keller University of Tulsa 12 Automatic repair of the filling tooth interface in dental restorations Chung Hao Lee University of Oklahoma 13 Personalized treatment of brain aneurysms Yu Mao Oklahoma State University 14 Dual function nanocoatings with drug release control Joshua Ramsey Oklahoma State University 15 Increasing the efficiency of cancer therapy drugs using smart nano sealed materials Hongwu Wang University of Oklahoma Health Sciences Center 16 A novel wearable vibration therapy device for treating upper limb functional impairment in stroke Cancer Research Natarajan Aravindan University of Oklahoma Health Sciences Center 17 Cre conditional RD3 loss driven neuroblastoma mouse model Novel tool for preclinical studies on disease evolution Binrui Cao University of Oklahoma 18 A dual function small protein identified by phage based biotechnology can smartly home to tumor sites and trigger the antitumor immune responses Victoria Christiansen University of Oklahoma Health Sciences Center 19 Does stopping blood vessel generation slow tumor growth Wei Qun Ding University of Oklahoma Health Sciences Center 20 Breast cancer cells secrete a protein that may regulate cancer migration Bethany Hannafon University of Oklahoma Health Sciences Center 21 Exosome microRNA contents are altered and contribute to breast cancer progression Blaine Mooers University of Oklahoma Health Sciences Center 22 New drug target for treating breast cancer Sangphil Oh University of Oklahoma Health Sciences Center 23 A protein that may be involved in the progression of pancreatic cancer 2
Maria Ruiz Echevarria University of Oklahoma Health Sciences Center 24 New therapies for prostate cancer Jie Wu University of Oklahoma Health Sciences Center 25 How cancer cells adapt to anti cancer drugs ZJ Zhao University of Oklahoma Health Sciences Center 26 Understand and treat blood cancers Cell Molecular Biology Dean Dawson Oklahoma Medical Research Foundation 27 Understanding the machine that distributes chromosomes when cells divide Paul DeAngelis University of Oklahoma Health Sciences Center 28 Understanding the glue between cells sugar protein connections Xi Qin Ding University of Oklahoma Health Sciences Center 29 Thyroid hormone and cone photoreceptor death Courtney Griffin Oklahoma Medical Research Foundation 30 How blood vessels regress Timothy Griffin Oklahoma Medical Research Foundation 31 A new metabolic link between obesity and osteoarthritis OA Shaoning Jiang University of Oklahoma Health Sciences Center 32 A mother s adverse nutritional status during pregnancy impacts her child s lifelong risk of metabolic diseases Ann Louise Olson University of Oklahoma Health Sciences Center 33 Increasing glucose uptake into skeletal muscle and adipose tissue can prevent type 2 diabetes Deepa Sathyaseelan University of Oklahoma Health Sciences Center 34 Role of an inflammatory cell death pathway in age associated inflammation Chemistry Biochemistry Marimuthu Andiappan Oklahoma State University 35 Development of novel nanocatalysts can lead to environmentally friendly and cost effective processes to produce pharmaceuticals Christina Bourne University of Oklahoma 36 A new approach to antibacterials activating bacterial timebombs Anthony Burgett University of Oklahoma 37 Making new anti cancer drugs that only target the cancer cells Kenneth Humphries Oklahoma Medical Research Foundation 38 Diabetes causes heart proteins to be abnormally modified Angus Lamar University of Tulsa 39 Using visible light activation to develop new tools for drug discovery and production Rakhi Rajan University of Oklahoma 40 A single conserved helix improves gene editing fidelity of multiple Cas enzymes Yihan Shao University of Oklahoma 41 Towards the design of new neuro and cardio protective drugs 3
Ann West University of Oklahoma 42 Deadly diarrhea Identifying the genetic regulatory networks Genomics Gene Expression Archana Unnikrishnan University of Oklahoma 43 Decreased food intake can change the genome function that can lead to beneficial effects Immunology Hongliang Li University of Oklahoma Health Sciences Center 44 An autoimmune pathophysiological and molecular mechanism in Polycystic Ovarian Syndrome Karla Rodgers University of Oklahoma Health Sciences Center 45 Keeping a check on B and T cell development Infectious Disease Dingbo Lin Oklahoma State University 46 Suppression of a mitochondrial gene may protect us from seasonal flu Shanteri Singh University of Oklahoma 47 Superbug bacteria are growing even stronger so we are making new drugs to fight back Instrumentation Data Sciences Clinical Evaluations Yong Chen University of Oklahoma Health Sciences Center 48 Listening for the invisible dose in cancer patients x ray induced ultrasound Guoliang Fan Oklahoma State University 49 Lead me follow me and walk with me Analyze your gait motion from a robot Tieming Liu Oklahoma State University 50 Can diabetic retinopathy be detected in early stage with routine blood tests Rajagopal Ramesh University of Oklahoma Health Sciences Center 51 Particles present in urine serve as a source for predicting treatment response in lung cancer patients Qinggong Tang University of Oklahoma 52 A new imaging guidance method that can make painless labor safer Hongwu Wang University of Oklahoma Health Sciences Center 53 A novel wearable vibration therapy device for treating upper limb functional impairment in stroke Neurobiology Shannon Conley University of Oklahoma Health Sciences Center 54 Impaired vascular smooth muscle cells contribute to brain aging Kathleen Curtis Oklahoma State University Center for Health Sciences 55 Excess weight gain and changes in brain areas after removal of ovaries Randall Davis Oklahoma State University Center for Health Sciences 56 A new medicine to treat mood and anxiety disorders Hamed Ekhtiari Laureate Institute for Brain Research 57 Brain rehabilitation for people with opioid and or meth use disorder Michael Elliott University of Oklahoma Health Sciences Center 58 Preserving vision and preventing blindness by better understanding immune responses in the eye 4
Beverley Greenwood Van Meerveld University of Oklahoma Health Sciences Center 59 Understanding chronic pain is it all in your head Calin Prodan University of Oklahoma Health Sciences Center 60 Changes in clotting cells after concussion may lead to increased risk for stroke many years after the injury Kelly Standifer University of Oklahoma Health Sciences Center 61 PTSD pain and anxiety Inflammation initiates symptoms Michael Stout University of Oklahoma Health Sciences Center 62 Estrogen actions in the male brain may delay disease onset Nutrition Psychology Public Health Matt Alderson Oklahoma State University 63 Understanding brain based causes of attention deficit hyperactivity disorder ADHD Joe Cecil Oklahoma State University 64 Virtual learning environments to support science learning for autistic students Jennifer Craven Oklahoma State University 65 Dads and the development of infants in Oklahoma DADIO Joanne Davis University of Tulsa 66 Insomnia post trauma nightmares and suicide risk Sam Emerson Oklahoma State University 67 Can fat tolerance testing be adapted for clinical use Carole Johnson University of Oklahoma Health Sciences Center 68 Low priced entry level digital hearing aids provide acoustic benefits and enhanced health related quality of life of older Oklahomans with low incomes Roger Kollock University of Tulsa 69 Determining if a firefighter is fit for duty Pavan Parikh University of Oklahoma Health Sciences Center 70 Reducing pain and improving movement by using Tylenol and ibuprofen instead of narcotics in mothers who undergo c sections Jamie Rhudy University of Tulsa 71 The Oklahoma study of native american pain risk part 2 OK SNAP II Karina Shreffler Oklahoma State University 72 Increasing mother s connection to their babies during pregnancy helps them to be healthier Stephanie Sweatt Oklahoma State University 73 Understanding difficulties with regulating emotions Matt Vassar Oklahoma State University Center for Health Sciences 74 How strong is addiction medicine research Michael Wimberly University of Oklahoma 75 Investigating the relationship between environmental exposures and cancer in Oklahoma Physiology Pharmacology William Berry University of Oklahoma Health Sciences Center 76 Scar tissue that forms after abdominal surgery may cause costly long term health problems 5
Anna Csiszar University of Oklahoma Health Sciences Center 77 Fighting for brain health in aging with antiaging supplements Syed Raziullah Hussaini University of Tulsa 78 Chemical probes for developing effective antismoking agents Ashish Ranjan Oklahoma State University 79 Heating of antibiotic loaded nanoparticles can clear painful bone infections William Sonntag University of Oklahoma Health Sciences Center 80 Why do we develop Alzheimer s disease in old age Zoltan Ungvari University of Oklahoma Health Sciences Center 81 Zombie cells cause learning and memory deficits in brain cancer patients who received radiation therapy Weidong Wang University of Oklahoma Health Sciences Center 82 Hunt for a new drug for the treatment of diabetes Jian Xu University of Oklahoma Health Sciences Center 83 New targets on blood vessels for metabolic syndrome Andriy Yabluchanskiy University of Oklahoma Health Sciences Center 84 Sepsis is associated with higher risk of death in older adults and higher incidence of memory loss in survivors 6
Biomedical Engineering Awasthi A new polymer to modify nanoparticles and suppress toxic immune reactions Immunokinetics of superhydrophilic polymer modified liposome encapsulated hemoglobin PI V Awasthi University of OK Hlth Sci Ctr Project HR17 054 Research Area Bio Med Eng Liposomes are commonly used nanoparticles for drug delivery and vaccine formulation SOLUTION OUR RESEARCH Coating of liposomes with special polymers can prevent this toxicity A new polymer called HDAS SHP for coating liposomes PROBLEM Naked or plain liposomes can cause severe toxicity in people ADVANTAGES OF HDAS PEG Better protection than customarily used polymers Completely synthetic and potentially not immunogenic Helps liposomes circulate in blood for long period of time FINDINGS HDAS SHP Evaluated stability of HDAS SHP on liposomes Plain liposome Coated liposome X Toxic Tested HDAS SHP liposomes in cells Assessed immune reactions in mice CONCEIVED APPLICATIONS Use HDAS SHP to coat liposomes containing hemoglobin for use as a blood substitute Replace traditionally used polymers in present day liposomes to improve their effectiveness 7
Azoug A Smart Skin to prevent Bed Sores Develop a Liquid Crystal Elastomer LCE skin to redistribute stress and prevent pressure ulcers PI Aurelie Azoug Oklahoma State University When patients are IMMOBILIZED for TOO LONG The only treatment is to move patients every 2 h Benefits of the Smart Skin Reduced treatment costs Improved quality of life Lesser need to move patients OCAST Project HR20 086 1 Research Area Biomedical Engineering They can die just by staying in a hospital bed their skin gets injured BED SORES Treating bed sores costs 11bn year We believe LCEs can help us We study LCEs and their unique mechanical properties Immobility has a heavy price Recent accomplishments Observing changes of properties inside LCE Developing a model under compression for simulations LCE during compression They can change shape without adding force They come back to their original shape 8 Simulation compressed LCE
Feng Understanding the Effects of Sphero Cylinder Drug Particle Shape to Enhance SmallAirway Drug Delivery for Better Emphysema Treatment Outcomes Elongated Sphero Cylinder Particles Can Enhance Delivery from Dry Powder Inhalers to Human Lung PI Yu Feng Oklahoma State University OCAST Project HR19 106 Research Area Biomedical Engineering 9
Ford Versypt Determining How Diabetic Kidney Disease Starts Computational Modeling of the Onset of Diabetic Kidney Disease PI Ashlee N Ford Versypt Ph D School of Chemical Engineering Oklahoma State University OCAST Project HR17 057 Research Areas Biomedical Engineering Chemistry Physiology Computational Biology 10
Harrison A new method for targeting and treating triple negative breast cancer with commonly used drugs linked to a protein Novel targeted protein drug conjugates for treating metastatic breast cancer combined with immunostimulation and mTOR inhibition PI Roger Harrison Ph D University of Oklahoma Delivering targeted chemotherapies to triple negative breast cancer TNBC remains a major challenge for oncologists and scientists But we can overcome this challenge by targeting a fat molecule called phosphatidylserine PS with the protein annexin to deliver drugs to the tumor OCAST Project HR19 148 Research Area Biomedical Engineering Recent Accomplishments TNBC cells have an excess of PS parking places for annexin to deliver drugs to the cancer cells Healthy cells have no PS parking places and annexin will not park on these cells 1 We confirmed the appropriate dosing schedule for both annexin drug conjugates in mice 2 Annexin Targets PS PS is like a parking place on the surface of cancer cells that is only reserved for annexin Annexin is like a delivery vehicle that delivers drugs to the tumor Annexin DM1 conjugate significantly increased survival in mice Benefits Decrease in chemotherapy side effects Increased survival of patients with metastatic breast cancer PS a fat molecule Annexin protein 3 Annexin chlorambucil conjugate significantly decreased tumor volume in mice Less drug needed to kill cancer cells Drug linked to annexin created with biorender com PS is found predominatly on the inner inner membrane of healthy cells but is expressed 11
Keller Automatic Repair of the Filling Tooth Interface in Dental Restorations Interfacial Healing in Dental Restoration PI Michael W Keller The University of Tulsa OCAST Project HR16 100 Research Area Biomedical Engineering Project Summary Resin based restorations have become the primary choice of most patients requiring restorative dental work This preference is based on appearance and a growing concern about the presence of mercury in dental amalgams While these restorative materials provide benefits composite resins are prone to failure The primary cause of restoration failure is damage at the resin tooth bond leading to the formation of new cavities A major research area is new strategies for improving material performance and for minimizing the potential of new cavity formation Material approaches are currently focused on the synthesis of new adhesive resin formulations that are resistant to degradation and attack by microbes Based on this work several additives have been suggested by researchers that improve the resistance of the restoration dentin bond to enzyme attack These approaches use passive materials or processes to improve the durability of the resin tooth bond These passive approaches attempt to inhibit degradation processes in order to prevent failure of the interface and eliminate subsequent pathogenic attack on the remaining healthy tooth structure In this project we will synthesize and characterize an active material that will respond to interface damage by healing and sealing interfacial cracking and failure Accomplishments Synthesized micron and submicron nanoscale microcapsules for inclusion at the tooth restoration interface Developed specimen preparation procedure to enable testing of the new selfhealing material Fracture testing of interfacial specimens is ongoing to determine efficacy of selfhealing Image of initial fracture specimen to test interfacial self healing 12 Schematic view of a tooth with caries and subsequent restoration Inset image shows the damage healing process for the proposed adhesive resin material A shows the pristine asplaced restoration B shows the onset of damage that ruptures capsules C shows the release and polymerization of the healing agent repairing and sealing the damage Image below the tooth is a micrograph of 1 micron and smaller capsules intended for self healing
Lee PERSONALIZED TREATMENT OF BRAIN ANEURYSMS HR 18 002 Novel Shape Memory Polymer Devices for Optimal Endovascular Embolization of Intracranial Aneurysms Research Area ______________________________ Dr Chung Hao Lee Dr Yingtao Liu Dr Bradley N Bohnstedt The University of Oklahoma BRAIN ANEURYSMS Balloon shaped Occur most Aneurysms can be We want to create deformation of frequently at the clipped off or filled personalized foams that arteries in the brain circle of Willis with coils fill the aneurysm Shape memory polymers SMPs can be compressed and recover their shape using heat stimulus Time 0s Compressed Time 0s Recovered 40 0 0 C Our SMPs release heat when short Our SMPs recover their shape and occlude electric currents are applied to them aneurysm models after electric stimulation COMPUTARIZED SIMULATIONS ALLOWED US TO UNDERSTAND INTERACTIONS BETWEEN OUR DEVICE AND THE BODY Untreated Before stimulation Treated After stimulation Changes in blood flow in treated Changes in temperature within treated aneurysms aneurysms during foam delivery NEXT STEPS Development of a device to transport the foam into the aneurysm catheter Assessment of interactions between the foam and aneurysm environment in vivo B O M C A C S A D B O M A T R A S 13 D S A B O R A T O R
Mao Dual function Nanocoatings with Drug Release Control Nanocoatings for Controlled Drug Release and Improved Biocompatibility PI Yu Mao Oklahoma State University OCAST Project HR18 005 Drug eluting stents widely used in treating coronary artery diseases Our research focuses on simultaneous control of drug release and stent biocompatibility Research Area Biomedical Engineering But burst drug release and lack of biocompatibility limits the clinical success burst release Accomplishments reduced platelet adhesion linear release Linear drug release no burst Regulation of drug release kinetics Improved biocompatibility with less platelet adhesion time days 14
Ramsey Increasing the Efficiency of Cancer Therapy Drugs Using Smart Nano Scaled Materials Targeted Delivery of a Reactive Oxygen Species Generator for Treatment of Hormone Refractory Prostate Cancer PI Joshua D Ramsey Oklahoma State University OCAST Project HR19 104 Research Area Biomedical Engineering Prostate cancer affects more than 1 in 10 men at some point in their lifetime and is the second leading cause of death among men Treatment options are limited and the side effects of using a reactive oxygen species generator such as glucose Glucose oxidase GOX is a cytotoxic protein that can be used for treating prostate cancer oxidase are high due to poor targeting and retention Our approach is to encapsulate GOX within a polymer matrix that is targeted to prostate cancer cells thereby limiting the side effects and Encapsulated GOX targeted to prostate specific membrane antigen protecting the enzyme GOX encapsulated in our novel drug carrier is six times more efficient than unencapsulated GOX Live cell assays compare the effectiveness of encapsulate GOX vs unencapsulated GOX 15
Wang A novel wearable vibration therapy device for treating upper limb functional impairment in stoke Development and evaluation of vibration based wearable upper limb rehabilitation device PI Hongwu Wang University of Oklahoma HSC OCAST Project HR18 034 Research Area Biomedical Engineering Project Highlights Functional recovery from neurorehabilitation only lead to 20 of patients fully resumption of their social life and job activities mainly due to underdoes Focal vibration FV therapy a non pharmacological non invasive treatment has had satisfactory outcomes as a useful tool in neurorehabilitation We are developing and evaluating a wearable and mHealth technology that delivers individualized and precise vibration to target muscles The device provides patients opportunity to apply the prescribed vibratory stimuli inhome and or at community settings to sustain the dosage needed It also allows therapists to monitor usage and compliance and to adjust based on progression Recent Accomplishments Image 1 The final prototype of the wearable vibration device and its hardware components Patients caregivers and therapists met virtually during COVID 19 pandemic to finalize the design and development A final prototype was fabricated and assessed by the patients caregivers and therapists An app and web portal was developed to track the device usage and remotely monitoring and adjusting the vibration Wearable Focal Vibration Device and Methods of Use 2020 Provisional Patent 62 991 562 16 Illustration of wearing the device to right arm by patient him her self Image 3 The web portal that allows therapist to remotely monitor and adjust the vibration regimen
Cancer Research Aravindan RD3 protein an unsung hero that can control the development of the deadly infant cancer Cre Conditional RD3 Loss Driven Neuroblastoma Mouse Model Novel Tool for Preclinical Studies on Disease Evolution PI Natarajan Aravindan OUHSC OCAST Project HR19 045 Research Area Cancer Research Biology Project Highlights Despite four decades of clinical and research efforts to combat neuroblastoma the most common cancer in infants cure for aggressive disease is challenging Neuroblastoma contributes to onetenth of all childhood cancer deaths We recognized the loss of a protein called Retinal Degeneration Protein 3 RD3 in aggressive tumors and also indicated that such loss plays critical role in cancer progression Here we are developing a novel preclinical mouse model by knocking out RD3 gene in select neural crest cells NCC unique cells in which this cancer arise during early development to study whether RD3 loss is required for onset of neuroblastoma and for its progression In the long run this research will lead to recognize the mechanism s of cancer initiation and progression and will allow us to develop improved therapeutic strategies for the cure of this deadly disease Recent Accomplishments Establishing preclinical mouse model to study whether loss of RD3 in select cells during development prompts the genesis of neuroblastoma Mechanisms how RD3 control tumor evolution Generating clinical disease mimicking mouse model to study whether RD3 loss aggravates neuroblastoma progression 17
Cao A dual functional small protein identified by phage based biotechnology can smartly home to tumor sites and trigger the antitumor immune responses Cancer immunotherapy by tumor homing immune checkpoint blocking dual functional peptide PI Binrui Cao University of Oklahoma OCAST Project HR17 043 Research Area Cancer Research Project Narrative Cancer cells can avoid antitumor immune responses by interacting with the switches called immune checkpoints Cancer immunotherapy is to block the immune checkpoints and induce antitumor immune responses However the current protein blockers may cause serious side effects This project aims to develop a novel anti tumor drug that can block immune checkpoints with minimum side effects and low production cost Our proposed drug is a dual functional peptide small protein composed of two components one forTEM image of bioengineered phage selectively recognizing tumor sites and another for blocking immune ELISA results showing that peptide has the highest affinity to is toto tumors GWHSPHAHWRVK checkpoints These dual functional peptidesOur couldresearch selectively move PD 1 in the presence of PD L1 competitor peptide HPLHHLRHATSW GSAA peptide and induce antitumor immune responses Moreover due to their develop a medicine withlower HPLH GSAARTISPSLL YTPW peptide YTPWASRLYPLY production complexity the production costs of peptides will be relatively low FHS peptide FHSHHNRPMKSP WPH peptide CANCER CELLS avoid immune responses Liwei Zhang a student in our lab constructs bioengineered phage Recent accomplishments Tumor targeting molecule was identified Switch blocking molecule Liwei Zhang a graduate student from our lab performed the co display of the PD 1 blocking was peptideidentified and the melanoma tumor homing peptide on a single phage by interacting with the SWITCHES both tumor targeting Recent Accomplishments and switch blocking We have identified a PD 1 blocking peptide capabilities GWHSPHAHWRVK that can bind with PD 1 in the presence of PD L1 The Benefits Smart cancer therapy WPHLQHHKATSR LTP peptide Low sideGWHS effects LTPHKHHKHLHA GWHSPHAHWRVK Control control peptide GLHTSATNLYLH Low production cost shows our peptide has the highest ELISA We have constructed a bioengineered phage cobinding affinity to the PD 1 target displaying of the PD 1 blocking peptide on the sidewall and the melanoma tumor homing peptide at the tip respectively to form the tumorhoming anti PD 1 phage or THaPD1 phage A bioengineered phage displaying two molecules was constructed We found that the melanoma tumor growth could The phage could inhibit be inhibited by our THaPD1 phage in the pretest growth phage TEMtumor image of bioengineered 18
Christiansen Does Stopping Blood Vessel Generation Slow Tumor Growth Does Prolyl Oligopeptidase Inhibition Suppress Tumor Growth Victoria Christiansen OUHSC Warren Research HR18 046 Blood vessel growth is NORMAL But in tumors It can lead to Tumor growth Our research focuses on understanding vessel growth and reducing SMALLER Recent Accomplishments Tumor size New cancer treatment Understanding vessel growth Staining of colon tumor showing bloodvessels green INCREASED Slowing vessel growth Benefits Cancer Research Cancer Biology mouse with tumors Recent accomplishments Animal experiment showing reduced tumor growth Staining tumors to show vessels cell death and enzyme presence 19 tumor formation Staining of colon tumor reveals enzyme presence red
Ding Breast cancer cells secrete a protein that may regulate cancer migration Exosome Mediated Transfer of Metastasis Associated Protein 1 in Metastatic Breast Cancer PI Wei Qun Ding University of Oklahoma Health Sciences Center MTA1 is found in vesicles secreted by breast cancer cells OCAST Project HR20 105 It can then be transferred to other cells surrounding the tumor or in distal organs MTA1 Primary cancer cells Other type of cells Research Area Cancer Biology By its name it relates to breast cancer metastasis Metastasis Associated Protein 1 MTA1 Benefit It could lead to new therapeutic and diagnostic strategies against metastatic breast cancer a major cause of breast cancer related death We study how vesicle associated MTA1 might contribute to breast cancer migration and whether the secreted MTA1 can serve as a diagnostic tool Recent accomplishment Established cell lines lacking MTA1 which allows us to study MTA1 s contribution to breast cancer progression Initiated collection of patient plasmas from NIH supported cooperative human tissue network CHTN under an approved IRB protocol 20
Hannafon Exosome microRNA Contents Are Altered and Contribute to Breast Cancer Progression The Role of Exosomes in Breast Ductal Carcinoma In Situ PI Bethany N Hannafon PhD OUHSC Invasive breast cancer often develops from a non invasive precursor called ductal carcinoma in situ DCIS Our research is focused on understanding the role of exosomes and their contents in DCIS progression OCAST Project HR17 052 We do not fully understand what drives DCIS progression to invasive breast cancer and we cannot predict when or if it will progress Microscopic images of fluorescently labeled tissue sections of mouse mammary glands with human DCIS left or invasive breast cancer right RECENT ACCOMPLISHMENTS DCIS progression is attenuated in a mouse model by blocking exosome secretion resulting in reduced circulating exosome miRNAs Electron microscopy images of exosomes isolated from breast cancer cells THE BENEFITS Summer undergraduate student researcher Kiera Vaughn University of Central OK and laboratory technician Matthew Bruns now a 1st year medical student at Oklahoma State University 21 Understand the biology of early breast cancer Identify biomarkers that can predict progression Develop ways to prevent progression Research Area Cancer Biology Exosomes are small extracellular vesicles secreted from cells that contain and transport small RNAs called microRNAs We will also determine whether changes in exosome microRNA contents are altered in patients with DCIS and invasive breast cancer PRESENT GOALS We are continuing to collect blood plasma samples to evaluate the exosome microRNA signatures in patients with DCIS and invasive breast cancer
Mooers New drug target for treating breast cancer Role of a Lysine Hydroxylase in Breast Cancer PI Blaine Mooers OUHSC The war on breast cancer is needs new weapons JMJD4 a lysine hydroylase is one such bad actor OCAST Project HR20 002 Research Area Cancer Research We need to stop enzymes that trigger the growth of tumors A drug could bind to its active site and block further harmful effects We found leads with the OU supercomputer We are checking them in the lab 22
Oh A protein that may be involved in the progression of pancreatic cancer Role of JMJD4 in Redox Regulation and Pancreatic Cancer PI Sangphil Oh University of Oklahoma Health Sciences Center Pancreatic cancer is VERY AGGRESSIVE OCAST Project HR17 067 Research Area Cancer Research SURVIVAL RATE It is RESISTANT 5 in US CHEMO THERAPIES to conventional We found JMJD4 protein is Ruicai Gu Ph D a postdoctoral fellow in our lab is culturing pancreatic cancer cells We will focus on understanding how JMJD4 regulates PANCREATIC CANCER PROGRESSION and validating JMJD4 as a NEW TARGET for pancreatic cancer therapy over expressed in a subset of pancreatic tumors The benefits reduce the mortality rate reduce costs of health care 23 Pancreatic cancer developed in mouse model Recent accomplishments Studying how JMJD4 promotes pancreatic cancer cell survival Evaluating JMJD4 s role in pancreatic tumor development using a mouse model system
Ruiz Echevarria New Therapies for Prostate Cancer Defining the role of the TMEFF2 transcript in androgen signaling in prostate cancer OCAST Project HR18 07 PI Maria J Ruiz Echevarria PhD Univ of Oklahoma Health Sciences Center Research Area Cancer Research Cancer Biology Prostate cancer is the second leading cause of cancer related death in men Current therapies for advanced prostate cancer are mainly directed to block the activity of a protein the androgen receptor which is essential for prostate cancer cell growth The problem targeting the androgen receptor leads to therapeutic resistance and development of a currently incurable and aggressive form of prostate cancer OUR SOLUTION OUR RESEARCH FOCUSSES ON IDENTIFYING NEW WAYS TO INDIRECTLY TARGET THE FUNCTION OF THE ANDROGEN RECEPTOR BY SIMULTANEOUSLY BLOCKING THE ACTIVITY OF MULTIPLE ASSOCIATED PROTEINS COREGULATORS THAT ARE NECESSARY FOR ITS FUNCTION Methods Using in vivo in vitro and bioinformatic approaches we have identified a series of small RNAs that simultaneously target and inhibit the expression of multiple androgen receptor coregulators ultimately blocking androgen receptor activity Results Expression of these small RNAs prevent prostate cancer cells and tumor xenograft growth and lead to cancer cell death Because they affect multiple targets development of therapeutic resistance is unlikely Expression of specific small RNAs inhibits growth of xenograft tumors in vivo HIGHLIGHTS We have identified small RNAs that target the expression of numerous genes which are significantly enriched for androgen receptor coregulators Expression of these small RNAs results in PCa cell death without affecting viability of benign prostate cell lines These sequences represent novel therapeutics for advanced PCa with potential for rapid translation into clinical trials These studies are currently under review in the Molecular Therapeutics Nucleic Acid journal 24
Wu How Cancer Cells Adapt to Anti Cancer Drugs Deciphering bypass mechanisms of resistance to SHP2 inhibition Jie Wu OU Health Sciences Center OCAST Project HR19 029 Research Area Cancer Research A new target and breakthrough drugs for cancer therapy Mechanisms of drug resistance KRAS driven lung tumors 1 Response 2 Resistance DEGs of resistant cells Vulnerability of resistant cells Combinational treatment 25
Zhao Understand and treat blood cancers Define the role of Mpl in myelofibrosis PI ZJ Zhao OUHSC OCAST project HR18 113 Research Area Cancer Biology Myelofibrosis is a type of blood cancer affecting the bone marrow There is no effective treatment for myelofibrosis Animal models of human diseases are very useful For studying molecular and cellular mechanisms Patients with myelofibrosis have a median survival of 5 years For identifying and testing therapeutic drugs We developed a transgenic mouse model of myelofibrosis and used it to identify potential drugs Mouse model of Bone marrow myelofibrosis myelofibrosis 26 Reduced myelofibrosis after drug treatment
Cell Molecular Biology Dawson Understanding the machine that distributes chromosomes when cells divide Orienting Chromosomes on the Meiotic Spindle PI Dean Dawson OMRF OCAST Project HR17 115 1 Research Area Cell Molecular Biology From Mom From Dad Our genes are arranged on 23 chromosomes We inherit a copy of each chromosome from each of our parents Cells with incorrect numbers of chromosomes are associated with cancer and birth defects Hoa Chuong a research technician in our lab evaluates cells in the microscope A machine of cellular cables and motors move the chromosomes so that when cells divide so that each new daughter cell gets the exact correct chromosome number Our research is focus on learning how does this machine move chromosomes with such accuracy and why does it sometimes makes mistakes Cell with fluorescentlymarked chromosome used to study cell division Recent accomplishments We developed a new assay to monitor the sliding of chromosomes along cellular cables called microtubules We found discovered that a controller of cell division affects shortening of the cables as they pull chromosomes Data from our OCAST project were used to procure a grant from the National Science Foundation to continue this project 27
DeAngelis Understanding the Glue between Cells Sugar Protein Connec9ons Tetherable Glycosaminoglycan Polymers for Insights into Matrix Cell Protein Interac ons PI Paul DeAngelis OUHSC Dept of Biochem Mol Biol OCAST Project HR18 104 Area Biochemistry Project Highlights How do you make mul cellular life Use a glue of sugar polymers and their protein binding partners to s8ck various cell types together Why study The glue is cri8cal for health and disease from normal development of the body s organs to spreading metasta8c cancer cells or to white cells homing to lymph nodes to ght infec8ons How to see We use custom made sugar polymers with handles to pull on the sugar while being bound by various proteins Single molecule atomic force spectroscopy allows us to watch a single interac8on so we can obtain an accurate molecular view Measuring the mechanical stability of sugar protein bonds of the glue Tissues are glued together with various proteins sugars schema8c Matrix Biology 2018 Vol 71 72 p 432 442 Recent Accomplishments The direc9onality of the sugar chain is important for binding Sliding of sugar chains through certain binding protein pockets allows mo8on Sugar protein interac9ons may behave similarly to some DNA repair and binding proteins but could use di erent mechanisms too Customized polymer constructs can be selec8vely grabbed at either end and pulled with a probe 8p orange The force and bond breakage are measured for various pairs of sugars red or black proteins receptor 28
Ding Thyroid hormone and cone photoreceptor death Exploration of the mechanisms underlying thyroid hormone signaling induced cone photoreceptor degeneration PI Xi Qin Ding University of Oklahoma Health Sciences Center The lightsensing cone photoreceptor cells are responsible for day light vision visual acuity and color vision https upload wikimedia org Photoreceptor degeneration affects millions of people around the world The vision of a patient with macular degeneration Excessive thyroid hormone activity induces cone photoreceptor death in a mouse model of retinal degeneration We will determine the cell stress responses to excessive thyroid hormone activity We will identify the death pathways contributing to cone death Thyroid hormone regulates cell growth and metabolism and has been associated with age related macular degeneration https www changeyegroup com macular degeneration Inhibition of thyroid hormone production protects cones in a mouse model of retinal degeneration Research Area Cell Molecular Biology OCAST Project HR20 045 The benefits Target thyroid hormone to prolong cone photoreceptor survival Improve life quality Reduce healthcare cost 29 Our research will focus on understanding how excessive thyroid hormone activity kills cone photoreceptors Recent accomplishments Study retinal cone photoreceptor structure using light and fluorescent microscopes Study retinal and cone photoreceptor function using electrophysiological recordings
Griffin How Blood Vessels Regress Investigation of the role of hypoxia in initiating hyaloid vessel regression PI Courtney Griffin OMRF Blood vessel overgrowth in the eye can cause blindness Our goal was to understand how hyaloids regress so we could trigger regression of overgrown vessels in diseased eyes OCAST Project HF18 014 1 We studied unique vessels called hyaloids in the mouse eye that naturally regress after birth Hyaloid vessels prior to regression in a newborn mouse eye We found a family of proteins that Hyaloid vessels become thin and have slow blood flow before they regress Findings This OCAST Postdoctoral Fellowship supported the research of Dr Chris Schafer Research Area Cell Molecular Biology Using a drug that inhibits the same family of proteins we caused overgrown vessels with slow blood flow to regress in diseased mouse eyes 30 disappeared in hyaloids immediately before they regressed Our research has important implications for the treatment of patients with retinopathies
Griffin A new metabolic link between obesity and osteoarthritis OA Role of diabetes induced lysine malonylation in chondrocyte metabolism and osteoarthritis PI Timothy M Griffin Oklahoma Medical Research Foundation OCAST Project HF18 022 Mechanics alone do not explain the obesity OA link Obesity increases knee OA and hand OA Post doctoral awardee Dr Shouan Zhu 2 out of 3 people with OA also have Metabolic Syndrome Physiology Pharmacology Our research tests a new theory of cell metabolic damage called carbon stress which describes how overnutrition causes metabolic byproducts to accumulate in cells bind to proteins and damage cell function We discovered that the enzyme that removes the malonyl lysine byproduct is produced at lower levels in OA cartilage 31 Image of this byproduct malonyl lysine in cartilage cells of diabetic mice Accomplishments Dr Zhu obtained a tenure track Assistant Professor faculty position in the Ohio University Musculoskeletal and Neurological Institute We presented findings at the Annual Meeting of the Orthopaedic Research Society Manuscript describing results is currently under review
Jiang A mother s adverse nutritional status during pregnancy impacts her child s lifelong risk of metabolic diseases Fetal epigenetic programming of mitochondrial biogenesis in diabetes during pregnancy the role of AMPK and microRNA 130b PI Shaoning Jiang OUHSC OCAST Project HR19 133 The risks for obesity can originate from prenatal exposure to adverse intrauterine environment Obesity facts Obesity is a serious global health problem that increases the risk of diabetes cardiovascular diseases non alcoholic fatty liver diseases and certain cancer More than 35 of adults had obesity in Oklahoma CDC data 2019 Goal of current work The proposed work will investigate the roles of a particular microRNA family called miR 130b 301b focusing on the roles in fat development and energy expenditure regulation Research Area Molecular Biology How the environment in the womb programs the baby to develop diseases later remain unclear miR 130b 301b miR 130b 301b was identified by unbiased screening to be linked to human metabolic diseases In animal models miR 130b 301b was increased by feeding pregnant mice with high fat diet Can be used as diagnostic marker and therapeutic target Approaches Genetic deletion of miR 130b 301b in mice as animal model Human primary cells from pregnant women will be studied Significance Discovered a new role of miR 130b 301b in suppressing brown fat development and energy balance miR 130b 301b can be a therapeutic target against obesity The studies will lead to better understanding potential molecular mechanisms underlying the long lasting outcomes in offspring of mothers with obesity or diabetes 32
Olson Increasing glucose uptake into skeletal muscle and adipose tissue can prevent type 2 diabetes Mechanisms regulating GLUT4 expression in obesity PI Ann Louise Olson OUHSC GLUCOSE GLUCOSE GLUCOSE Blood glucose enters cells when GLUT4 proteins orange move from inside the cell to the surface We use a special screening tool to find a protein that will specifically help the cell make more GLUT4 protein by increasing the GLUT4 messenger RNA that is used by ribosomes to synthesize protein OCAST Project HR17 018 GLUCOSE GLUT4 Protein With diabetes it takes more insulin than normal to move GLUT4 to the surface If we make more GLUT4 in the cells we can help insulin do its work GLUCOSE GLUCOSE The amount of glucose that enters the cell increases with more GLUT4 proteins Our goal is to help cells make more GLUT4 The protein that we discovered is called znf467 This protein works in the nucleus to help the gene that codes for GLUT4 to be transcribed into GLUT4 mRNA that is then used for the protein synthesis by the ribosome ribosomes GLUT4 mRNA Research Area Cell Molecular Biology GLUT4 mRNA znf467 GLUT4 Gene 33 Ann L Olson PhD Professor of Biochemistry Molecular Biology College of Medicine
Sathyaseelan Role of an inflammatory cell death pathway in age associated inflammation Testing the Role of Inflammation in Aging and Age related Diseases PI Deepa Sathyaseelan OUHSC OCAST Project Number HR18 053 Research Area Physiology Pharmacology Chronic inflammation termed sterile inflammation or inflammaging inflammation in the absence of detectable pathogens is a common feature of aging and ageassociated diseases Our research will focus on understanding whether inflammaging is causing aging and age associated diseases and pathway s that mediate inflammaging are not known Necroptosis is a newly identified form of cell death that causes inflammation however role of necroptosis in inflammaging is unexplored The study will help us to identify whether necroptosis is a key pathway in inflammaging The study could be translationally important because pharmacological agents that inhibit necroptosis are available 34 Recent accomplishments Blocking necroptosis in Sod1 KO mice using necroptosis inhibitor Necrostatitin 1s reduced necroptosis and markers of fibrosis markers in the liver of Sod1KO mice Blocking necroptosis reduced liver tumor incidence in a mouse model of diet induced liver cancer
Chemistry Biochemistry Andiappan Development of novel nanocatalysts can lead to environmentally friendly and costeffective processes to produce pharmaceuticals Copper Nanocatalyst as Efficient Heterogeneous Photocatalyst for Continuous Syntheses of Pharmaceuticals through Cross Coupling Reactions Dr Marimuthu Andiappan Oklahoma State University OCAST Project HR18 093 Research Area Chemistry Biochemistry Highlights Carbon Carbon C C coupling reactions are widely used reactions in the pharmaceutical industry These reactions are conventionally performed using expensive and toxic palladium Pd catalysts and hazardous solvents such as dimethylformamide DMF The objectives of this project include the development of inexpensive and less toxic nanocatalysts that can perform C C couplings in green solvents The performance of Cu2O nanoparticles catalyst in green solvents i e EtOH and Acetonitrile compared to the conventional hazardous DMF solvent Transmission electron miscroscopic image of Cu2O nanoparticles Recent Accomplishments We developed inexpensive and comparatively less toxic cuprous oxide Cu2O nanoparticles as a catalyst to perform C C coupling reactions in green solvents such as ethanol EtOH and acetonitrile Inexpensive and less toxic Cu2O nanocatalyst and green solvents EtOH and acetonitrile can be potentially used as replacements for conventional expensive and toxic Pd catalysts and hazardous DMF solvent The findings can be potentially used to develop new pharmaceuticals manufacturing processes These new processes can exhibit a number of benefits including i reduced manufacturing cost ii improved drug product quality and iii reduced waste generation compared to the conventional processes using Pd catalyst and DMF solvent 35
Bourne A new approach to antibacterials activating bacterial timebombs Targeting bacterial cell metabolism by manipulating toxin antitoxin systems PI Christina Bourne OU Dept of Chem and Biochem Annually in the US AMR causes 2 mill infections 23 000 deaths 2019 CDC Hotspot of interaction identified OCAST Project HR17 099 Research Area Infectious Disease Approach Activate endogenous bacterial toxins Sustained activation will promote self killing of bacteria Recent Advances Need Expanded treatment options to address growing burden of antibacterial resistance Identified where to target to weaken this tight picomolar interaction Demonstrated this increases antitoxin removal Highlights how to manipulate this TA system Toxin Antitoxin systems from P aeruginosa New Knowledge Pre existing in How to manipulate bacterial pathogens protein interactions A toxin protein promote ParE neutralized by toxin inhibition of binding to an DNA gyrase immunity protein 36 Grad student Kevin Snead working on experiments 1 8 crystal structure of TA system from P aeruginosa PDB ID 6xrw
Burgett Making New Anti Cancer Drugs That Only Target the Cancer Cells Synthesis and Drug Development of ORP4 Protein Inhibitors A New Route to Precision Anti Cancer Therapeutics PI Anthony Burgett University of Oklahoma OCAST Project HR17 116 Research Area Chemistry and Biochemistry Novel Anti Cancer Compound OMe Me 25 Me Chemical Synthesis HO 3 OH 2 3 4 OH O Me 22 19 O 18 O O 5 O H Me 17 Me 1 OH OH 2 9 1 AcO 4 O O H 16 1 5 5 6 H Molecular Drawing of the Anti Cancer Compound OSW 1 Medicinal chemists working Green Cells Are Dying Cancer Cells Compound Targets Novel Cancer Specific Protein ORP4 Cancer Cells Killed by Compound Treatment Potential New Cancer Specific Therapeutic 37
Humphries Diabetes is a significant health concern in Oklahoma We are studying how diabetes affects the heart Our research focuses on mitochondria Diabetes promotes heart disease The powerhouse of the cell Electron microscope image of mitochondria from heart cells We visualize heart cells from diabetic healthy and diabetic mice Dr Kenneth Humphries head of the research project RECENT ACCOMPLISHMENTS healthy and we determine how diabetes affects the cells ability to produce energy from different nutrients like sugar and fats S F Sugar S Fat F Generation of a new mouse model that is helping us understand how diabetes affects mitochondria Submission of a grant to NIH New method to determine how diabetes affects mitochondrial proteins 38
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Rajan A Single Conserved Helix Improves Gene Editing Fidelity of Multiple Cas Enzymes Protein engineering to develop stringent CRISPR Cas genome tools PI Rakhi Rajan University of Oklahoma CRISPR Cas system is a bacterial adaptive immune system OCAST OCASTproject project HR20 103 HR20 103 Research area Chemistry and Biochemistry CRISPR Cas has biomedical relevance DNA cleavage by Cas9 HOW WHY It inserts a small piece of the intruder DNA into the bacterial genome to create memory of past infections The inserted DNA creates guide RNA that helps Cas proteins to cleave intruder DNA Created by BioRender RNA guided DNA cleavage mechanism has been repurposed into powerful gene editing tools and is being pursued for gene therapy applications Cas9 won the Nobel Prize in 2020 due to these potentials CRISPR Cas has undesirable effects Undesirable effects can be removed PROBLEMS GOAL Cas proteins can cleave target DNAs that are not completely matching the guideRNA causing debilitating off target effects during gene editing applications Create stringent Cas protein variants with reduced off targeting by modulating the interactions of a highly conserved bridge helix with RNA and DNA Focused on mutating bridge helices of Cas9 and Cas12a two proteins commonly used for gene editing applications Different positions along the helix will be tested to locate the best protein constructs for gene editing A gel showing DNA cleavage selectivity A graph showing efficiency of gene editing ACCOMPLISHMENTS Created protein variants with reduced off target DNA cleavage while maintaining comparable on target DNA cleavage Cell based gene editing experiments were setup to test these variants efficiency in editing diverse genes 40 METHODS
Shao Towards the Design of New Neuro and Cardio Protective Drugs Rational Development of Selective and Potent Inhibitors to Pro apoptotic Bax Protein Yihan Shao University of Oklahoma HR18 130 Chemistry and Biochemistry Computational Biology C e ll D e a t h Bax proteins form holes on mitochondria outer membranes Bax inhibition Target Protein promises to slow rapid neuron death Design of Potent Ligands Computer Modeling Organic Synthesis Biological Testing Binding Pocket down unwanted cell deaths Bax Lead Compounds Lead Optimization Analogs of SRG 025 and other lead compounds SRG 025 41 are being synthesized and tested
West Deadly diarrhea Identifying the genetic regulatory networks Two component signal transduction in the human bacterial pathogen Clostridioides difficile PI Dr Ann West University of Oklahoma OCAST Project HR18 110 Research Area Chemistry Biochemistry C difficile Infection CDI C difficile uses sensor kinase and response regulator proteins to surveil its surroundings and adapt to the host environment Each year in the US CDI causes 500 000 illnesses We study these proteins to understand how C difficile responds to nutrient availability adjusts its lifestyle and initiates spore formation 1 in 11 adults age 65 die of CDI within 1 month Research Impact These proteins are potential targets for development of new antibiotics that will decrease the risk of recurrent CDIs 1 in 6 have recurrence in 2 8 weeks Recent Accomplishments Created a strain of C difficile with an RR_1586 homolog gene deletion Obtained quantitative binding data for RR_1586 to target genes Examined growth of C difficile under various nutrient limitation conditions Determined crystal structure of RR_1586 Savannah Morris Graduate Student Phosphatase reporter assay for RR_1586 42
Genomics Gene Expression Unnikrishnan Decreased food intake can change the genome function that can lead to beneficial effects Role of DNA methylation in Dietary Restriction mediated Cellular Memory Archana Unnikrishnan University of Oklahoma OCAST Project HR17 098 Research Area Genomics Gene Expression Project Highlights Food restriction referred as Dietary Restriction DR retards aging and extends lifespan DR could impart beneficial effects through DNA methylation a genetic modification that regulates gene expression and is critical during development and aging The purpose of this project is to determine the effect of dietary restriction on DNA methylation in the intestinal cells If we can show that a short period of DR is sufficient to impart life long beneficial effects this would be an important discovery because short term DR would be a more compliant approach translationally than the rigorous lifelong regimen Gene Gene inactivated Gene Gene activated Gene Promoter Figure 2 How DNA methylation works Methylation of gene regions promoter inactivates the gene and if the regions are not methylated the gene is active DNA Methylated region Unmethylated region Dietary Restricted Control Figure 1 24 month old C57BL 6 mice fed either ad libitum control or life long dietary restricted diet throughout life Recent Findings Short term DR alters DNA methylation levels and gene expression in the intestine DR increases intestinal stem cell numbers Short term DR enhances intestinal stem cell function Figure 3 Different Cell types of the intestine from 24 months old mice fed ad libitum or lifelong DR diet analyzed using single cell gene expression analysis DR increases stem cell numbers Green Stem cells Red Paneth Cells Brown Goblet cells Orange Enterocytes Purple Fat cells 43 Figure 4 Short term DR increases stem cell function DR increased intestine regeneration in culture from stem cells obtained from young Y and old O AL and DR mice fed DR for 4 months 4X magnification
Immunology Li An autoimmune pathophysiological and molecular mechanism in Polycystic Ovarian Syndrome An antibody to a Pituitary Receptor May Induce Ovary Cysts and Infertility 07 01 2017 06 30 2020 PI Hongliang Li Department of Medicine OUHSC OCAST Project HR17 123 GnRHR AAb is present as a contributor to the pathophysiology in PCOS subjects PCOS a metabolic and reproductive disease may have a autoimmune etiology GnRHR AAb enhanced LH pulsatile function T production and increased inflammatory cytokines The RID peptide will prevent the binding of GnRHR AAb and normalize the HPO axis Blocking effects of RID peptide Recent accomplishments Human study Cell culture Animal study The RID peptide will alleviate several components of the PCOS phenotype 44
Rodgers Keeping a check on B and T cell development Regulation of RAG2 chromatin interactions during V D J recombination OCAST Project HR18 072 Research Area Immunology V segments To fight infections our immune system uses a vast repertoire of antibodies made in B cells and T cell receptors made in T cells This repertoire is made at the genetic level by the RAG1 and RAG2 proteins in a process known as V D J recombination J segments RAG1 RAG2 V J Functional gene Sometimes mistakes in V D J recombination lead to certain types of leukemias or lymphomas FL H3K4me3 Our research is on how V D J recombination is normally regulated so that mistakes are prevented WeT490A use fluorescence H3K4me3 to visualize microscopy RAG2 FL labeled with a green probe in pre B cells This image shows one pre B cell H3K4me3 labeled with a red probe is a protein bound to the genome Arrowheads show examples of colocalization Full length RAG2 D E rich PHD 52 7 1 6 bladed propeller non core 48 1 core 41 0 44 6 Recent Accomplishments We have identified specific regions in RAG2 that regulate its interaction with the genome Disruption of this regulatory function results in overactive V D J recombination which can lead to genomic instability antibody RAGs are needed to put together the antibody genes in B cells 35 2 PI Karla K Rodgers PhD T490 Regulates RAG2 genome interactions 45
Infectious Disease Suppression of a mitochondrial gene may protect us from seasonal flu carotene 9 10 oxygenase 2 BCO2 in acute respiratory distress syndrome PI Dingbo Lin Oklahoma State University OCAST Project HR17 114 Research Area Nutrition Seasonal flu One of the top health concerns worldwide People with flu may have a hyperactivation of the immune system Lead to fever chills shortness of breath which caused by acute lung inflammation Dietary regulation of the immune responses can be a new way to protect you from the flu BCO2 An enzyme that can cleave carotenoids It is located in the inner membrane of mitochondria Lack of this gene led to an accumulation of carotenoids mitochondrial dysfunction and lowgrade inflammation Natural killer cells Important immune cell that responds to virus infection knockout of BCO2 genes leads to natural killer cell population increase Inflammatory cytokines Produced by immune cells during virus infection Short time large quantities of cytokines release will cause organ damage or death Knockout of BCO2 genes may weaken the cytokine storm Virus replication Flu virus enter the nucleus and replicate its DNA Inhibition of flu virus replication may protect people from flu Lack of BCO2 genes may suppress virus replication Increases in animal survival rate 46 Lin
Singh Superbug bacteria are growing even stronger so we are making new drugs to fight back The development of daptomycin analogs PI Shanteri Singh University of Oklahoma OCAST Project HR19 080 Anyone can get a bacterial infection but it s getting harder and harder to cure them Resistant bacteria like MRSA and VRSA are becoming more common and they are starting to resist our most powerful drugs Structure of daptomycin Research Area Infectious Disease Daptomycin DAP is one such drug We use it as a drug of last resort so it s saved for only the nastiest of infections Electron micrograph image of MRSA courtesy of the National Institute of Allergy and Infectious Diseases We want to make DAP more effective against these superbugs by changing its structure but we must account for its complex construction Even so some bacteria have begun to resist it We have found that some of these versions can kill the resistant bacteria almost 80x more effective than normal daptomycin Using enzymes we ve made several versions of DAP with slightly different structures Now we are trying to make our enzymes more efficient at creating the best versions With fully optimized enzymes we can start pushing back against the rising threat of superbugs 47
Instrumentation Data Sciences Clinical Evaluation Chen Listening for the Invisible Dose in Cancer Patients X ray induced ultrasound Real time dosimetry in external beam radiation therapy with X ray acoustic computed tomography XACT PI Yong Chen University of Oklahoma HSC OCAST Project HR19 313 Research area Biomedical Engineering RADIATION DOSIMETRY IS A CRUCIAL PROCESS FOR CANCER PATIENTS UNDER RADIATION THERAPY TO ENSURE THAT THE CORRECT DOSE IS ACCURATELY DELIVERED TO THE DESIRED LOCATION XA A schematic of an XACT dosimetry system including in room detector signal preamp and amplifier and post data processing software An example of measured XACT signal vs delivered dose from PI s previous publication Water phantom measurement shows very promising ultrasound signal and 3D reconstructed dose from 16x16 2D detector array in water for a metal target 48
Fan Lead me follow me and walk with me analyze your gait motion from a robot A Mobile Platform for Clinical Gait Analysis PI Guoliang Fan Oklahoma State University OCAST HR18 069 Research Area Data Science Clinical Platform Can we use lowcost consumer RGB D depth sensor for clinical gait analysis Can we analyze a walking person s gait from different perspectives for clinical gait analysis on the go Our research will focus on advanced computational approaches to improve noisy skeleton data for clinical gait analysis We are developing a mobile platform with motion data capture capability that is able to analyze a person s gait from different perspectives Recent accomplishments The benefits Affordable portable Better accuracy More efficient Versatility flexibility Reduce healthcare cost 34 improvement on 3D joint position estimation 25 improvement on bone length estimation 40 improvement on joint angle estimation 49
Liu Can diabetic retinopathy be detected in early stage with routine blood tests Validating a clinical decision support algorithm developed with big data to diagnose state prevent and monitor a patient s diabetic retinopathy PI Tieming Liu Oklahoma State University OCAST Project HR18 087 Research Area Health Data Analytics Currently a comprehensive eye examination is required for diabetic retinopathy DR diagnosis Unfortunately patient compliance rate with the recommended eye exam is very low at only 40 As a result about 25 of diabetic patients with DR remain undiagnosed across the US Unfortunately the current therapies can only halt DR progression and vision loss cannot reverse it This research is to develop and validate a widelyavailable and cost effective tool for DR screening Recent Accoplishments We used the Cerner Health Facts EHR Database Cerner Corporation to develop a DR predictive model with a few primary care lab results demographic and comorbidity data We validated the model using the Healthcare Enterprise Repository for Ontological Narration HERON from University of Kansas Medical Center The model had an accuracy of 78 We presented our research at the 2020 HHDC Research Symposium and won the second place 50 Cerner Health Facts EHR Database Requiring only a few widely available variables this predictive model will be deployed as a non invasive cost effective tool for DR screening
Ramesh Particles present in urine serve as a source for predicting treatment response in lung cancer patients Non invasive liquid biopsy approach for using exosomes as a surrogate for determining response to immunotherapy in lung cancer patients PI Rajagopal Ramesh How can a physician quickly know if a cancer patient is responding to treatment OCAST Project HR 18 088 Exosomes are small particles
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Wang A novel wearable vibration therapy device for treating upper limb functional impairment in stoke Development and evaluation of vibration based wearable upper limb rehabilitation device PI Hongwu Wang University of Oklahoma HSC OCAST Project HR18 034 Research Area Biomedical Engineering Project Highlights Functional recovery from neurorehabilitation only lead to 20 of patients fully resumption of their social life and job activities mainly due to underdoes Focal vibration FV therapy a non pharmacological non invasive treatment has had satisfactory outcomes as a useful tool in neurorehabilitation We are developing and evaluating a wearable and mHealth technology that delivers individualized and precise vibration to target muscles The device provides patients opportunity to apply the prescribed vibratory stimuli inhome and or at community settings to sustain the dosage needed It also allows therapists to monitor usage and compliance and to adjust based on progression Recent Accomplishments Image 1 The final prototype of the wearable vibration device and its hardware components Patients caregivers and therapists met virtually during COVID 19 pandemic to finalize the design and development A final prototype was fabricated and assessed by the patients caregivers and therapists An app and web portal was developed to track the device usage and remotely monitoring and adjusting the vibration Wearable Focal Vibration Device and Methods of Use 2020 Provisional Patent 62 991 562 53 Illustration of wearing the device to right arm by patient him her self Image 3 The web portal that allows therapist to remotely monitor and adjust the vibration regimen
Neurobiology Conley Impaired vascular smooth muscle cells contribute to brain aging The role of vascular smooth muscle cell plasticity in age related cognitive decline Shannon Conley OUHSC HR18 118 In aging people develop cognitive impairment and gait defects often progressing to diseases such as Alzheimer s Disease and Related Dementias Research Area Cell Biology AGING Decreased IGF 1 Our research focuses on understanding the role of decreased hormonal signaling via IGF 1 on vascular smooth muscle cells VSMCs in the development of agerelated cognitive decline Maladaptive VSMCs Decreased proliferation and hypertrophy Decreased ECM remodeling secretion of protective factors Increased apoptosis senescence Increased inflammation oxidative stress Altered response to mechanical stress Mid Large Vessels Microvessels Recent highlights Knocking out the IGF 1 receptor in aged hypertensive mice leads to worsened vascular damage shown by development of cerebral microhemorrhages CMH Defective autoregulation Increased hemodynamic in response to hypertension and cellular stress Regional vascular instability CMHs Blood brain barrier disruption Microvascular rarefaction Vascular Cognitive Impairment and Dementia Alzheimer s Disease and Related Dementias Gait Disorders Decreased Healthspan Benefits Our studies are shedding light on the crucial mechanisms that underlie age related vascular disease in the brain Understanding the cellular and molecular changes that lead to vascular cognitive impairment is essential to be able to develop targeted therapeutics to retard age related cognitive decline 54 brain section showing CMH brown Increased CMH in these mice leads to decline in regularity index a sign of impaired gait
Curtis Excess weight gain and changes in brain areas after removal of ovaries Neuroimmune activation and weight gain in a rat model of postmenopausal obesity PI Kathleen S Curtis Oklahoma State University Center for Health Sciences Research Topic Neurobiology OCAST Project HR18 089 Obesity is one of the most common health conditions and leads to serious health issues including diabetes and heart disease The prevalence of obesity increases as people age especially in women after menopause Obesity is poorly understood but it is known that the brain detects hormones and other signals to decide what when and how much we eat Are there changes in brain areas that control body weight after menopause Our team is attempting to answer this question using female laboratory rats that have had their ovaries removed to eliminate their reproductive hormones which affects how much we weigh adapted from NCHS Data Brief no 360 Female rats rapidly gain weight after removal of the ovaries Immunohistochemical methods to examine neural right and non neural left cells in brain areas involved in controlling body weight HIGHLIGHTS Female rats rapidly and reliably gain weight after surgical removal of the ovaries Western blots of proteins in brain areas involved in controlling body weight Development of this postmenopausal weight gain is associated with changes in brain areas involved in controlling body weight 1 neural and non neural cells 2 receptors for gut hormones that change during weight gain and eating 3 neuroimmune signals Importantly these changes occur in at different times during the weight gain so may be linked to the development of obesity Wheel running reduces the weight gain but the effect is temporary and does not persist when exercise is terminated Female rats voluntarily exercise on running wheels These studies will allow us to identify factors that change early during postmenopausal weight gain or at particular phases of the weight gain rather than with established and extreme obesity Ultimately the information will help to target these factors in attempts to better manage or prevent obesity 55
Davis A new medicine to treat mood and anxiety disorders Advancing therapeutic options for treating mood and anxiety disorders using a novel anti inflammatory agent PI Randall L Davis Oklahoma State Univ Center for Health Sciences Research Area Neurobiology OCAST Project HR18 033 About 30 million people in the U S suffer from MOOD Extreme social stress or AND ANXIETY bullying can lead to DISORDERS and or worsen MOOD AND ANXIETY DISORDERS vietnaminsider vn Greatschools org Alzet com INFLAMMATION in the brain plays an important role in MOOD AND ANXIETY DISORDERS shutterstock Sebastian Kaulitzki RSD BULLYING INCREASED ANXIETY LIKE BEHAVIOR RSD BULLYING AFFECTED INFLAMMATORY SIGNALING IN THE BRAIN AND OTHER ORGANS BETA FNA WAS PROTECTIVE IN SOME INSTANCES MORE STUDIES ARE NEEDED 56
Ekhtiari Brain Rehabilitation for People with Opioid and or Meth Use Disorder Neurocognitive Empowerment for Addiction Treatment NEAT A Randomized Controlled Trial for Opioid and or Meth Addiction Hamed Ekhtiari MD PhD PI Robin Aupperle PhD CI Laureate Institute for Brain Research HR18 139 Neurobiology Addiction to opioids and methamphetamine are associated with brain deficits Brain deficits in memory attention decision making and control disturb normal daily functioning and attempts for abstinence There has been a relative lack of research focused on developing interventions targeting brain deficits in the context of addiction The aim of this study is to develop and test clinical efficacy for an intervention targeting these brain deficits Brain Gym NEAT workbook cover We use cartoons as a tool to communicate with patients Accomplishments in 2020 Brain Gym NEAT cognitive architecture in 16 sessions Cognitive modules are added gradually to each other from simpler to more complex ones 57 Completed the RCT intervention for the first four groups of the clinical trial n 45 and completed 1 year follow up for the first three groups Paused new recruitments for the trial in March 2021 due to the pandemic but accomplished to do the follow ups with remote assessments Made revisions in the study protocol to adjust for remote assessments and potentials for teleconference intervention and received IRB approval in August 2020 Restarted recruiting new participants for the 5th group since November 2020
Elliott Preserving Vision and Preventing Blindness by Better Understanding Immune Responses in the Eye The Role of TRAF3 in Retinal Function and Inflammation PI Michael Elliott DMEI OU Health Sciences Center OCAST Project HF18 008 For healthy eyes vision Inflammation can be Research Area Neurobiology GOOD BUT Too much INFLAMMATION Inflammation in the retina must be balanced can cause blindness Our research focuses Mouse models This OCAST Postdoctoral Fellowship supported the research of Dr Jami Gurley on a gene called help us mimic inflammatory eye diseases and its role in retinal Microscopes help us visualize the retina inflammatory diseases so we can study Immune Cells that Because our studies suggest that Traf3 PROMOTES INFLAMMATION damage to the retina immune responses cause 58 treatments that Traf3 ACTIVITY may help prevent retinal damage blindness
Greenwood Van Meerveld Understanding Chronic Pain is it all in your head Central epigenetic reprogramming of amygdala receptor expression in stress induced chronic pain PI Beverley Greenwood Van Meerveld Ph D University of Oklahoma Health Sciences Center OCAST PROJECT HR 18 040 Research Area Neurobiology STRESS Can make you SICK The Benefits Better understanding of belly pain in women New behavioral treatments targeted to women Improve quality of life of women with daily belly pain Fewer lost work days by women and can cause Daily Belly PAIN Especially in women THE G U T B R AIN A XIS Our research focuses on understanding the central molecular mechanisms that contribute to belly pain in females Recent Accomplishments Exposing female rats to stress increases belly pain Showing that stress alters gene expression in the brain Testing the mechanisms underlying the effectiveness of environmental enrichment to treat belly pain 59
Prodan Changes in clotting cells after concussion may lead to increased risk for stroke many years after the injury Thrombotic and inflammatory mechanisms in traumatic brain injury PI Calin Prodan MD OUHSC OCAST Project HR19 111 Research Area Neurobiology Traumatic brain injury TBI is common What we have discovered Occurs in almost 2 million people in the United States each year Most cases are mild traumatic brain injuries concussions Although mild these injuries are linked to a long term increase in the risk for stroke later in life patients with concussions during military service have increased levels of clotting cells coated platelets years after the last injury these levels were linked to inflammation Patients with the highest levels clotting cells were most likely to have silent strokes on MRI The proposed work investigate how previous concussions lead to increased inflammation higher levels of clotting cells and silent strokes long before severe strokes The results of the proposed work may lead to potentially new therapies to prevent stroke and help us understand how best to protect the brain in those at risk for concussion Coated platelets on microscope green platelet receptor red fibrinogen What we have done Brain scans MRI with silent vascular changes see blue arrows After a delay due to the COVID pandemic we restarted our project as a collaborative approach that involves the VA Medical Center OUHSC and OU Norman We finalized a protocol for obtaining repeat brain scans with MRI scans in individuals with concussions and prior scans We have now developed specific research protocols that will allow our research team to access selected patients with documented concussions Active recruitment with pandemic precautions is ongoing 60
Standifer PTSD Pain and anxiety Inflammation Initiates Symptoms Post traumatic stress disorder and Co morbid chronic pain Evidence that TNF initiates a sequelae involving Nociceptin Orphanin FQ N OFQ PI Kelly Standifer OU College of Pharmacy OCAST Project HR17 041 Research Area Neurobiology 61
Stout Estrogen actions in the male brain may delay disease onset Role of hypothalamic estrogen receptor in 17 estradiol mediated metabolic benefits PI Michael Stout University of Oklahoma HSC Estrogens are more abundant in females 17 estradiol extends lifespan in male mice OCAST Project HR20 024 but have also been found to act in males which we hypothesize occurs by signaling In the brain We administer 17 estradiol to the that have had their brain of male estrogen receptors mice removed using genetic tools 62 Research Area Neurobiology We study the hypothalamus in the brain We Remove Estrogen Receptors in Male Mouse Brain Understanding this biology will 1 Tell us if males and female develop diseases differently 2 Tell us is estrogen signaling in the male brain can be used as a treatment strategy potentially in humans
Nutrition Psychology Public Health Alderson Understanding brain based causes of attention deficit hyperactivity disorder ADHD Neurocognitive Deficits Underlie ADHD PI R Matt Alderson Oklahoma State University ADHD is a chronic disorder of childhood and adulthood INSERT PIC OCAST Project HR17 051 ADHD affects 3 5 of school age children at an annual U S cost of illness of over 36 billion Recent research has sought to identify underlying causal mechanisms of ADHD Clinical psychology doctoral students preparing the memory task The bene ts Better understanding of ADHD causes Research Area Psychology Depic on of neurons ring This research sought to identify speci c previously unexamined neurocognitive processes that underlie or cause ADHD Recent Accomplishments Identi ed ADHD related neurocognitive de cit not previously known to the eld Allows for development of new non pharmacological interventions Findings help explain context speci c impairments Allows for improved teaching objectives 63
Cecil Virtual Learning Environments to support science learning for autistic students Investigation of Impact of Virtual Reality based cyber learning approaches PI J Cecil Oklahoma State University Focus is on Helping autistic children learn science OCAST PROJECT HR18 077 Research Area Public Health Learning robotics concepts Learning Solar Systems concepts Creating 3D Virtual Reality Environments to help students learn science and engineering A VLE to learn robotics concepts View of an assembly VLE Haptic device Learning assembly robotics path planning and other topics Initial Assessment results have indicated the positive impact of such VLE based approach on helping autistic students learn STEM Autistic Elementary middle high school students are benefiting 64 A VLE to learn assembly concepts using Moon Mission contexts
Craven Dads and the Development of Infants in Oklahoma DADIO Family Hormonal Profiles of Resilience Defining Fathers Roles in Infant Biosocial Development PI Jennifer Byrd Craven Oklahoma State University Fathers play an important role in infant development OCAST Project HR17 003 We know little about how fathers impact stress response system development The benefits Identification of Molecular structure of cortisol released in response to stress and one of the primary hormones of focus This longitudinal study will identify how fathers and mothers contribute to stress system coordination with their infants and each other Research Area Psychology Public Health protective factors against stress and disease Nikki Clauss former graduate research assistant processes saliva samples for cortisol CRP testosterone and progesterone Recent accomplishments Salivary assays for stress hormones and inflammation Molecular structure of C Reactive Protein CRP a marker of inflammation 65 Families assessed when infants are 4 12 and 18 months old
Davis Insomnia Post Trauma Nightmares and Suicide Risk CBT I versus ERRT Impact on Sleep Nightmares and Suicidal Ideation PI Dr Joanne L Davis University of Tulsa OCAST Project HR17 087 Research Area Nutrition Psychology Public Health Oklahoma has the 10th highest suicide rate in the country and suicide is the 9th leading cause of death in the state The ongoing nightmare research conducted at TU Research finds an association between suicidality and sleep disturbances and nightmares While many studies have found that sleep disturbances in general are related to suicidality there appears to be a unique relationship between the experience of nightmares and suicidality Currently there are two evidence based sleep treatments that have shown to be effective in improving nightmares sleep quantity and quality and related psychopathology Cognitive Behavioral Therapy for Insomnia CBT I and Exposure Relaxation and Rescripting Therapy ERRT TITAN is the organization providing the space for this research trial We are interested in examining whether treating insomnia and nightmares may lead to a reduction of suicidal ideation Treatment manual for ERRT RECENT ACCOMPLISHMENTS Extensive recruitment efforts have been made in the Tulsa area 13 participants have been randomized to receive either CBT I or ERRT treatment 6 of them have completed treatment Preliminary results have found that both of these treatments reduce the severity of suicidal ideation over 50 66
Can Fat Tolerance Testing Be Adapted for Clinical Use Emerson Validity and Reproducibility of Clinically Feasible Postprandial Testing PI Sam R Emerson PhD Oklahoma State UniversityStillwater Award HR20 027 Research Area Nutrition Psychology Public Health HIGHLIGHTS Fat tolerance testing which involves consuming a high fat shake and measuring the blood fat triglyceride response may be clinically useful for screening for heart or liver disease risk Fat tolerance testing is not feasible for a clinical setting We developed an abbreviated fat tolerance test that one day could be used in clinics worldwide as a cardiometabolic risk screening tool This study is determining the validity and reproducibility of our new fat tolerance test in order to ensure the results are trustworthy When utilized in a widespread manner the abbreviated fat tolerance test may detect cardiometabolic disease risk earlier leading to better health outcomes and lower healthcare costs In this study blood lipids are measured before and after consumption of a high fat meal in order to test the validity of a new fat tolerance test Our fat tolerance test only requires two blood draws fasting and 4 hours after the meal We are comparing results against a traditional fat tolerance test that requires 7 blood draws over 6 hours Image Credit MedlinePlus gov RECENT ACCOMPLISHMENTS This study was activated October 1 2020 Since then 5 participants completed the study Ten more participants are enrolled to complete the study in early 2021 67
Johnson Low priced entry level digital hearing aids provide acoustic benefits and enhanced health related quality of life of older Oklahomans with low incomes Health related Quality of Life Benefits from Advanced Digital Technology Hearing Aids Carole E Johnson PhD AuD PI HERO Lab Dept Communication Sciences and Disorders College of Allied Health OUHSC HR 16 118 PROJECT NARRATIVE RECENT ACCOMPLISHMENTS Figure 1 Experimental design with RCT and longitudinal components to the study Control HHIE Change Benefit Score Figure 3 Those in the treatment group had a greater mean hearing handicap reduction change score the lower the change score the greater the reduction of hearing handicap on the HHIE after 8 weeks of wearing hearing aids than the control group p
Kollock Determining if a firefighter is fit for duty Fit for duty An Examination of the Efficacy of the Physical Abilities Test in Determining Physical Readiness PI Roger Kollock The University of Tulsa To help minimize the risk of CASUALTIES OCAST Project HR18 054 Research Area Nutrition Psychology Public Health firefighters are often required to complete an annual PHYSICAL ABILITIES TEST PAT Firefighter performing a WFI stepmill test of aerobic capacity Firefighter performing an isometric midthigh pull to test muscle strength The benefits Evidence from this project will help support the ongoing measures to enhance physical readiness evaluation methods The PAT is used to help determine if firefighters are fit forduty Our research explored if the PAT is an indicator of physical readiness Recent accomplishments 1 manuscript in review Evaluation of squat mobility and stability 69 6 scientific abstracts presented at national and regional conferences
Parikh Reducing pain and improving movement by using Tylenol and ibuprofen instead of narcotics in mothers who undergo csections Towards Enhanced recovery after Cesarean Scheduled Post Operative Medications a Randomized Controlled Trial PI Pavan Parikh OUHSC OCAST Project HR20 122 70 Research Area Public Health
Rhudy The Oklahoma Study of Native American Pain Risk Part 2 OK SNAP II Does Glucose Dysmetabolism Contribute to Native American Pain Disparities A Pilot Study PI Jamie Rhudy PhD The University of Tulsa OCAST Project HR18 039 Research Area Psychology Native Americans NAs have a higher prevalence of chronic pain than any other U S racial ethnic group Diabetes also disproportionately affects this population This project examines whether glucose dysregulation may contribute to pain risk in Native Americans Testing uses state of the art methods to assess the nervous system peripheral fibers central sensitization pain inhibitory processes pain perception Peripheral A delta fibers are being assessed from contact heat evoked potentials evoked from the distal leg A sensor is applied to the back of the leg to record a marker of central sensitization spinal cord hyperexcitability Pain inhibitory processes are tested using a pain inhibits pain paradigm Accomplishments Data collection started March 2019 To date 26 individuals have completed testing Data collection was paused following pandemic onset but has now resumed Pain perception is assessed from a painfully cold circulating water bath 71
Shreffler INCREASING MOTHERS CONNECTION TO THEIR BABIES DURING PREGNANCY HELPS THEM TO BE HEALTHIER ENHANCING MATERNAL FETAL BONDING TO PROMOTE HEALTHY PREGNANCIES AND REDUCE ADVERSE PERINATAL OUTCOMES PI Karina M Shreffler Oklahoma State University OCAST Project HR19 129 Research Area Health Research Pregnant women who feel more attached to their babies engage in healthier behaviors Our study tests an intervention designed to enhance maternal prenatal bonding Bonding is critical for infants WOMEN WHO HAVE AN UNINTENDED PREGNANCY ARE AT PARTICULAR RISK FOR LOW POSTPARTUM BONDING WHEN THEY HAVE LOW PRENATAL BONDING BLOOM Video 1 INTERVENTION GROUP PARTICIPANTS IN THE TREATMENT GROUP ENGAGE IN A 2 WEEK INTERVENTION USING EXPLAINER VIDEOS Preliminary results THE BLOOM INTERVENTION INCREASED PRENATAL ATTACHMENT OVER A 2 WEEK PERIOD PI KARINA SHREFFLER TRAINS GRA TARA WYATT ON ENROLLMENT AND STUDY PROCEDURES PRE COVID 19 Recent Accomplishments Survey planning and programming into REDCap is complete participant payments are set up in the ClinCard system GRAs are fully trained Due to the COVID 19 pandemic our study protocol shifted to a fully virtual study This change resulted in the development of explainer videos since GRAs could not explain the intervention in person Video production is expected to be complete by 1 31 21 72
Sweatt Understanding Difficulties with Regulating Emotions Identifying a Direct Path to Emotion Dysregulation in Borderline Personality PI Stephanie N Mullins Sweatt Oklahoma State University OCAST Project Number HR 18 079 Research Area Psychology Broad Impact Emotion dysregulation ED is directly related to significant and serious negative health outcomes such as suicide substance misuse and risky sexual behavior This research will broadly impact the field of psychopathology by gaining a precise understanding of the pathway to ED Identification of prototypic emotions example Long term Identify the pathways to test the direct route from emotion sensitivity to heightened negative and unstable affect Understanding the biopsychosocial mechanisms by which components of ED interact to produce negative outcomes will inform interventions Carpenter Trull 2012 Model of Emotion Dysregulation Facial morphing sensitivity task examples 73 Recent Accomplishments Successfully recruited 18 individuals in Year 2 prior to disruptions by COVID19 which stalled data collection Participants completed Session 1 and 2 momentary assessment and emotion discrimination tasks Developed protocol for online administration for Year 3
Vassar Reproducible research can be independently performed replicated and verified Year 1 50 of addiction clinical trials sampled 244 of 487 were found to be at high risk of having bias in the study design Year 2 50 of systematic reviews sampled 5 of 10 could not have the summary effects approximated by replicating the study methods Year 3 Evaluate spin and financial conflicts of interest in addiction medicine systematic reviews Transparency with potential conflicts of interest reduces bias and increases reliability of results 74
Wimberly Investigating the Relationship between Environmental Exposures and Cancer in Oklahoma Improving Geocoding of Cancer Registry Data and Development of a Spatiotemporal Database of Environmental Exposures Michael C Wimberly U of Oklahoma OCAST Project Number HR16 04 Project Highlights Oklahoma has the 11th highest age adjusted cancer mortality rate in the US It is important to have accurate address data to understand potential environmental and behavioral risk factors for cancer Development of an environmental database provides a single location for multiple types of environmental contaminants to facilitate health research By better understanding the distribution of cancer in Oklahoma we can work with policy makers to enhance prevention and screening areas in high risk locations and populations Theme Administrative Air Industrial Land Physical Characteristics Water Total Total 4 15 3 7 31 53 113 Data items by theme in the environmental exposure database1 Research Area Public Health Distribution of Oklahoma Central Cancer Registry cancer cases not geocoded to the street level Why Is This Work Significant Recent Accomplishments Completed an environmental exposure database for Oklahoma1 Completed geocoding Oklahoma Central Cancer Registry and University of Oklahoma Central Cancer Registry Geocoding Compiled data on residential history Next step Complete spatial analysis of geocoded cancer data 1 Dilekli N Gopalani SV Campbell JE Janitz AE A geospatial environmental concentrations database of Oklahoma United States In Press at Data in Brief August 2019 75 We improved geocoding of Oklahoma Central Cancer Registry records by 40 These new data will help us to better understand the types of environmental exposures that increase cancer risk
Physiology Pharmacology Scar tissue that forms after abdominal surgery may cause costly long term health problems The Role of PDGF Signaling Mechanotransduction Nexus in the Development of Peritoneal Adhesions OCAST Project HR20 131 PI William L Berry OUHSC The Problem 90 of all patients have internal scar tissue peritoneal adhesions that forms following surgery Healthcare associated costs to treat peritoneal adhesions exceed 1 billion annually One of the most prevalent cell types found in peritoneal adhesions are called myofibroblasts brown cells in Figure 1 Myofibroblasts secrete the material necessary to form peritoneal adhesions Figure 1 Smooth muscle alpha actin SM A positive myofibroblasts brown stain Research Area Physiology Pharmacology The Approach Smooth muscle alpha actin has been shown to be positively regulated by the proteins MRTF A and MRTF B which are regulated in part by platelet derived growth factor PDGF signaling SERVIC ES Myofibroblasts express MRTF A and MRTF B Figure 2 Targeting these proteins may prevent or reverse myofibroblast formation Figure 2 Myofibroblasts in adhesive tissue express the genes responsible for MRTF A left and MRTF B right 76 The Results Hypothesis Blocking MRTF A B will reduce the expression of genes necessary for myofibroblast formation We utilized lentiviral vector technology to block MRTF A B which reduced the expression of important genes critical to the formation of myofibroblasts Figure 3 Therapies to reduce MRTF A B expression may be beneficial in patients undergoing abdominal surgery Figure 3 Blocking MRTF A B reduces the expression of SM A in human patient derived peritoneal adhesion myofibroblasts hAF Berry
Csiszar Fighting for Brain Health in Aging with Antiaging Supplements Novel Mechanism of Age Related Cerebrovascular Dysfunction PI Anna Csiszar University of Oklahoma Health Sciences Center OCAST Project HR 18 092 Research Area Physiology Clinical Problem Cerebral blood flow is essential for the maintenance of normal neuronal function and becomes progressively impaired during aging increasing the risk for vascular cognitive impairment NAD is a rate limiting cosubstrate for anti aging enzyme SIRT1 which is a key regulator of mitochondrial function cellular redox homeostasis and vascular function With age cellular NAD availability decreases which is a critical driving force in aging processes NAD biosynthesis by treatment with nicotinamide mononucleotide NMN reverses age related dysfunction in multiple organs NMN NMN imrpoves learning and memory processes in mice models of aging NMN increases blood supply to the brain NMN rejuvenates the expression of mitochondrial genes improving brain health NMN treatment is reversing age related decline in mitochondrial function Potential Solution NMN treatment improves blood supply to the brain cells and restores healthy brain function in aging 77
Hussaini Chemical probes for developing effective antismoking agents DISCOVERY OF INDOLIZIDINE 237D ANALOGS AS SELECTIVE 6 NICOTINIC RECEPTOR ANTAGONISTS PI Syed Raziullah Hussaini The University of Tulsa OCAST Project HR18 049 Research Area Physiology Pharmacology 78
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Sonntag Why Do We Develop Alzheimer s Disease In Old Age Susceptibility to Amyloid Oligomers in Response to Aging and Insulin IGF 1 Resistance PIs William Sonntag PhD Sreemathi Logan PhD OCAST Project HR18 120 Alzheimer s Disease only occurs as people get OLDER University of Oklahoma HSC Research Area Cell Molecular Biology Treatments for Alzheimer s Disease MUST understand mechanisms of aging Increased amyloid 1 42 levels are part of the mechanisms of Alzheimer s Disease why Our research finds that AND Older animals are very sensitive to amyloid Younger animals are resistant to the effects of amyloid The resilience of younger animals may be related to levels of IGF 1 Understanding the key interactions of age and disease is critical to human health 80 Promoting Healthy Aging
Ungvari Zombie cells cause learning and memory deficits in brain cancer patients who received radiation therapy Irradiation induced cognitive decline role of endothelial senescence PI Zoltan Ungvari OUHSC OCAST Project HF19 028 Research area Neurobiology CLINICAL PROBLEM Radiation therapy is a common treatment option in brain cancer patients Long term side effect of radiation therapy Memory and learning impairments in 40 50 of survivors HOW WE ADDRESSED IT Radiation Our lab developed a mice model mimicking the clinical doses of radiation to understand why it affects learning and memory Radiated mice showed poor blood flow responses to the brain Our research will focus on understanding how radiation affects the cells lining the blood vessels of the brain so we can devise drug targets to prevent this adverse side effect of radiation RESEARCH HIGHLIGHTS Our results showed that radiation causes DNA damage leading to premature aging of the cells aka Zombie cells lining the blood vessels in the brain Eliminating zombie cells using drugs aka senolytics improves blood flow responses and memory in radiated mice Imaging method to assess blood flow responses in mice brain POTENTIAL SOLUTION New treatment to prevent radiation induced side effects to the brain Improve the quality of life of cancer survivors Potential to apply the current findings for age related memory decline 81
Wang Hunt For A New Drug For The Treatment Of Diabetes Pancreatic beta cell protection of natural product K50 and its mechanism of action PI Weidong Wang OUHSC OCAST Project HR17 097 Research Area Physiology Pharmacology People with Diabetes have high blood glucose levels Beta cell area is Akita saline decreased in diabetes Diabetes affects 400 million people globally Akita Khellin More beta cells better blood glucose control Beta cells in the pancreas produce insulin to control blood glucose Our research aims to discover new drugs that C57B 6 increase beta cell area Akita saline A new chemical Akita Khellin K50 increases beta cell area K50 treatment C57B 6 lowers blood glucose in diabetic mice 82 Recent accomplishments K50 protects against beta cell death K50 suppresses ER stress
Xu New Targets on Blood Vessels for Metabolic Syndrome Endothelial regulation of high fat diet induced obesity PI Jian Xu OU Health Sciences Center OCAST Project HR17 046 FACTS Research Area Physiology Pharmacology HYPOTHESIS Obesity 3rd major cause of poor health 1st malnutrition 2nd infectious diseases Targeting a blood vessel protein improves obesity associated metabolic diseases Functional blood vessels are essential in health FINDINGS Mice fed a high fat diet loss a blood vessel protein and become obesity Therapeutic production of this protein improves metabolism in obese mice Manna Li MD PhD a Research Associate in our lab was staining blood vessels in the fat to identify therapeutic targets 83
Yabluchanskiy Sepsis is associated with higher risk of death in older adults and higher incidence of memory loss in survivors Prevention of sepsis induced multiple organ failure in old age PI Andriy Yabluchanskiy MD PhD OCAST project HR17 070 1 Research area Physiology Sepsis develops when bacteria or other infection organisms get into the bloodstream and spread throughout the body Sepsis is the tenth leading cause of death in patients over the age of 65 About 50 of sepsis survivors over the age of 60 develop progressive loss of memory The mechanisms that underlie this memory loss are currently unknown Control WebMD com We know that brain requires constant blood supply when neurons are activated Sepsis Our studies show that the coordination between active neurons and blood supply is altered in sepsis representative image on the left Control Sepsis In fact it appears that sepsis reduces appropriate blood supply during periods of intensive neuronal activity almost by 30 calculations are on the right Image on the right shows that aorta from septic animals does not relax as good as the one from control non septic animal Our ndings suggest that sepsis leads to generalized impairment of vascular health which may be the leading mechanism behind development of multiple organ failure 84 Relaxation We also found that blood vessels are compromised not only in the brain but in larger vessels such as aorta too 100 Sham 80 Sepsis 60 40 20 0 20 10 9 8 7 6 log10 ACh M 5 4
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