A note from Will
A note from Will
There is an entire ecosystem of bacteria, fungus and
virus that resides within each of us. This complex community of microbes, who call our intestines home, is
collectively referred to as the microbiome. As scientists and clinicians uncover more about the biology
of the microbiome we are finding that changes in this
community may have a role in causing or worsening
intestinal diseases such as Inflammatory Bowel Disease
(IBD), diabetes, gastrointestinal cancers, and even neurological diseases like Autism and Multiple Sclerosis. We are just
beginning to scratch the surface in the understanding of the microbiome and its role in disease. It is my belief that this microbial world harbors a number of
important potential discoveries that can help us treat these diseases.
These next few pages will introduce you to the work that my laboratory is pursuing, research that I feel is important, thoughtful and will one day bring real solutions to complex
diseases. I believe firmly in transparency and openness, particularly in science, so before
you continue reading about my scientific endeavors, I would like to introduce myself. It is
important to me that you know a little about who I am not only as Dr. William DePaolo
“the scientist,” but also as Will, a son, a brother, a husband and a friend.
Growing up Italian
I was born in Portland, Maine into a large Italian-American family. Being only third generation American those
strong Italian traditions of family are ideals I still hold
very close. I grew up in the kitchens of my grandparents. If I wasn’t helping out at my grandfather’s pizzeria then I was in the kitchen with my grandmother
making spaghetti sauce. I remember how they always
told me that I had to go to college, that I had to become
educated so that unlike my family who came to America, poor and
struggling, I could have a strong future. These memories did inspire me
to go to college, to become the first DePaolo to get a college degree
and then the first DePaolo to get a PhD. None of my grandparents
were able to celebrate these accomplishments with me. I lost all four
of my grandparents to cancers and heart disease and diabetes before I
graduated from college. I lost them to diseases that should be
treatable, that we should be able to cure.
I talk a lot, but I also listen
I was one of those loud, talkative, curious children who was always less interested in what they were supposed to be doing, and
more interested in how what they were supposed to be doing
was going to affect activities the next day. I grew up to be a
loud, talkative, curious adult who is also more interested
in how today’s findings will impact science or life in
the future. I have always been a talker, I used to
talk so much that my school teachers would send
me home with my unfinished lunches and notes saying “Your son did not eat lunch today, he was too busy
talking.” Sometimes, I was made to stand against a wall at
recess because I was distracting other students during class.
I still talk a lot, but I also listen. I am able to relate to those
people around me. As an adult this skill has allowed me the
opportunity to establish important connections, to bridge
different disciplines in science, and to initiate fruitful collaborations that otherwise may not have occurred. In the end,
all of that time in the kitchen talking and cooking with my
grandparents, and all of that talking during class helped to
shape me a scientist and as a man.
Microbial Isolation & Cultivation
CMiST will synergize with existing resources within the University of Washington, Department of Medicine,
to establish a unique set of tools and reagents that can be used by clinicians and researchers to address the
complex relationship between intestinal microbiota and host tissues in diseases such as Inflammatory Bowel
Specifically, we will:
Isolate bacterial species within the microbiota of
patient samples using standard culturing paired
Identify isolated bacteria using MALDI-TOF mass
Establish a repository for clinical and research isolates obtained from patients and healthy controls.
Equipment & innovations:
Link isolates to clinical patient data and/or existing
tissue in the GI biorepository, which will enable investigators to study the disease phenotype, tissue
status and bacterial response from the same patient.
Cultivate and prepare isolates and/or commercially
available probiotics strains for in vivo and in vitro
Provide resources and training to investigators who
want to expand their microbiology programs.
SHEL LAB Bactron anaerobic bacterial chamber, MALDI-TOF mass spectrometer
Bruker MALDI-TOF microflexTM
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a technique used in mass spectrometry that allows
for the analysis of both biological molecules (such as DNA, proteins, peptides and sugars) and large organic molecules (such as polymers, dendrimers and other macromolecules). Though the MALDI-TOF microflexTM
is fairly compact, just a little bigger than a PC tower, its capabilities are
huge. With this piece of highly specialized equipment, we will be able to
identify single bacterial species in just a few minutes.
SHEL LAB BACTRON900 anaerobic chamber
With the capacity to house 900 plates, the BACTRON900 will allow us to successfully cultivate a
number bacteria species, often difficult to grow, that live only within the confines of our intestine.
Host & Microbe Interaction
With this service, we will explore the immunological and genetic consequences of the microbiome when in
contact with human cells. Normally, we co-exist with the 100 trillion bacteria that call our bodies home. However, genetics and/or extrinsic factors (e.g. infection, diet) can influence this relationship and cause changes
leading to the development or exacerbation of inflammatory intestinal diseases. Understanding the complex
tug-of-war between host and microbe is critical in our ability to develop therapies to treat disease.
Specifically, we will:
Provide functional assays examining the response
of human cell lines and human/mouse organoid
cultures against purified bacterial isolates, metabolic by-products and/or mixed bacterial populations
Generate or acquire fluorescent probes against specific bacterial members of the microbiota in order to
visualize their relationship with each other as well as
with the intestinal tissue using fluorescent microscopy.
Screen potential drugs and microbiome-derived biotherapeutics using functional assays.
Determine gene induction of host and microbiota
using fluorescence microscopy paired with laser
Equipment & innovations:
Novel assays, Leica fluorescent microscope, organoids developed from IBD and healthy intestinal tissue,
16S fluorescent in situ hybridization (FISH)
With just a tiny tissue sample, we have the ability to actually grow three-dimensional intestinal organoids
or “mini-guts” as they are known here in the lab, in less than a week. These mini-guts retain key features of
the intestinal epithelium, including all of the major epithelial cell types, making them an ideal tool to help us
isolate and understand the different mechanisms at play in IBD versus healthy intestinal tissue.
Novel functional assays
–omics data predicts biological “function” of the microbiome based upon theoretical models, which may
potentially ascribe incorrect characteristics to a community. Our lab has developed assays that can determine the immunological signature induced by the microbiota. These assays can also be used to test
potential biotherapeutics or synthetic drugs on blocking microbiota-host immune interactions.
Other equipment available
LI-COR Odyssey CLx Imaging System
Two OMNI Bead Ruptors
The Odyssey CLx Imaging System utilizes
near-infrared fluorescence (NIR) light, a relatively recent optical imaging method, to provide digital images that are at both consistent
and reproducible. Because this imaging technique offers great sensitivity, it produces images of very high quality, giving us the ability to
confidently analyze samples more clearly and
The OMNI Bead Ruptor is simply a bead mill
used to homogenize tissue samples for molecular extraction. While simple in function, it is
the most advanced homogenizer on the market. With the capacity to hold 24 samples at
once, the Bead Ruptor gives our researchers
the ability to grind and lyse samples effectively and efficiently.
CMiST Associated Facilities and Services
GI Division biorepository
Microbiome, probiotics and stool transplants have entered pop culture
and the mainstream media, but is correct and accurate information
being circulated? In an era where Tweets reach hundreds and
thousands of people instantly, and where information is at the tip
of our fingers, it is critical that the information regarding health,
disease and the microbiome come from legitimate sources
providing factual information.
We will establish relationships with UW arts and film departments in order to educate local communities about health
and the microbiome using art, film and writing. An emphasis
of this initiative is to reach under-served populations regarding the importance of the microbiome and nutrition and health
Introducing Bioartist Kathy High
As part of our art and science initiative world-renowned bio-artist, Kathy
High, will be doing an artist residency in DePaolo Lab during winter 2016.
Kathy is an artist, but also a person who suffers from inflammatory bowel disease.
Her passion for trying to understand this complex disease is part of her art. Kathy has been commissioned to do an art exhibition in Fall of 2017 with a focus on IBD and the microbiome. As
part of her experience she will be joining the DePaolo lab and CMiST as an artist
in residence during the winter of 2016. Kathy has shown her work across the
US, as well as Australia, Germany, Poland, Spain, Ireland and the UK, and is
a Guggenheim fellowship recipient.
“Don't keep forever on the public road, going only where others have gone, and following
one after the other like a flock of sheep. Leave the beaten track occasionally and dive into the
woods. 'Every time you do so you will be certain to find something that you have never seen
before. Of course it will be a little thing, but do not ignore it. Follow it up, explore all around
it; one discovery will lead to another, and before you know it you will have something worth
thinking about to occupy your mind. All really big discoveries are the results of thought.”
-Alexander Graham Bell