to raise new questions, new possibilities, to regard old problems from a new angle requires creative imagination and marks real advance in science.

-Albert Einstein

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. 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 to

cancers, 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 was one of those loud, talkative, curious children who was always less interested in what they were sup-posed 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 lunch and notes saying “Your son did not eat lunch today, he was too busy talking,” or would make me stand against the wall at recess because I was distracting other students during class. I still talk a lot, but found that I also listen, and 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, I guess all of that time in the kitchen with my grandparents, all of those recesses I was made to stand against the wall

for talking during class, and all of those uneaten lunches shaped a scientist and as a man.

Dear potential donor, There is an entire ecosystem of bacteria, fungus and virus that resides with-in each of us. This complex community of microbes, who call our intes-

tines 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 Inflammato-

ry 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.

Thank you for considering a monetary gift to help fund the research in my lab. 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. You are investing in my research and trusting that your donation is “for a good cause,” so I

will share with you exactly what projects are being performed in my lab and how your donations will be used to further these initiatives. But before you continue reading about my scientific endeavors, I would like to introduce myself.

Current Research

Our body is home to over 100 trillion bacteria, most of which reside within our intestine.

While these bacteria out number our cells by a ratio of 10 to 1, there is still little known about their

influence on disease. Factors such as genetics, diet and infections influence, and even re-shape, this

complex community. Sometimes this can lead to imbalances, whereby an unhealthy bacteria is

able to overwhelm one’s system and promote inflammation and disease.

I believe it is imperative to understand how both genetics and environmental factors, such as nu-

trition, influence the microbiome. With this understanding, we hope to develop microbiome-based

bio-therapeutics and identify novel risk factors that can be used to treat disease.

Colorectal cancer

Nutrition & metabolism

Inflammatory bowel disease

Cutting edge technologies & innovations

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Infectious disease & vaccination

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Overview

Inflammatory bowel diseaseHuman genetics, the microbiome & IBD

In collaboration with Children’s Hospital LA, Keck and LA County hos-pitals, we are examining the intricate dialogue between human genes, immunity and the microbiome. With access to these patients we can evaluate the differences and similarities between both adults and children with IBD. Using patient samples we are working to develop assays to test human stool. With this knowledge we maybe be able to not only predict disease, but also the response patients may have to different treatments.

IBD tissue bio-bank

As part of our collaboration with Children’s Hospital LA, Keck and County hospitals, we have begun collecting tissue and detailed patient information on a small scale. An extensive IBD bio-bank would give us access to an invaluable collection of samples. Using these samples we can design specific studies that will give us insight into the biology behind IBD. These samples will be made available to all of the brilliant and talented scientists and physicians in the USC biomedical research com-munity, in hopes to inspire new collaborations and bridge different areas of science and medicine in order to discover new treatments for patients who suffer with IBD.

Colorectal cancer

Colorectal cancer (CRC) is the third most common form of cancer in men and women in the United States and the second leading cause of cancer-related death. All that sepa-rates the microbiome from our underlying tissues is a single layer of intestinal epithelial cells. This layer is re-populated by a unique stem cell at the bottom of each villi. Replica-tion and cellular division must be tightly controlled or can-cer can occur. Our group has discovered that recognition of our healthy microbiota is necessary for normal stem cell turnover and differentiation. Current research is focused on identifying the cellular and molecular events leading to disruption of this normal cellular turnover leading to colon cancer.

Immune-mediated signals controlling cellular turnover & cancer progression

Despite enormous health benefits in vitro and in animal models, probiotics have not done well in clinical trials of human disease. We have identified a specific sensor in our immune system that recognizes a component of a probiot-ic bacteria and induces a potent anti-inflammatory effect. Using this probiotic we have been able to suppress colorec-tal cancer progression.

Microbiome-derived biotherapeutics to treat colorectal cancer

Current research is aimed at1) Identifying the specific probiotic molecule(s) sensed by our immune system. 2) Producing this molecule synthetically in order to have a novel microbiome-based drug that can suppress the devel-opment of colon cancer and other inflammatory diseases.

Metabolism & nutrition

1) Determine whether the standard dietary intervention can reverse the fat deposition and liver pathology in NAFLD. 2) Compare the standard of care dietary intervention to a diets high in fiber or supplemented with probiotics.

3) Determine whether the effects of the diet are mediated by changes in the microbiome.

Dietary interventions in pediatric non-alcoholic fatty liver disease (NAFLD)NAFLD is a condition in which significant levels of fat builds up in the cells of the liver leading to a wide spectrum of liver diseases such as cir-rhosis and steatosis (infiltration of liver cells with fat). In the United States almost 10% of all children and 17% of 15-19 year olds have NAFLD. The need for improved diagnosis and treatment of NAFLD in children is high-lighted by the multiple complications these children are at high risk of developing, including atherosclerosis and other cardiovascular complications.

The goals of this research project are

Infectious disease & vaccination

Immunological scarring is the permanent alteration of subsequent immune responses following an acute infection due to changes in the microbiome. We are currently investigating how small mutations that occur within our genes may affect immunological scarring and whether this could set the stage for inflammatory bowel disease or other chronic inflammatory diseases.

Host genetics as a contributing factor to immunological scarring & development of inflammatory disease

Poor diets and living conditions are thought to contribute to the low efficacy rate of oral vaccines in sub-Saharan Africa. In Africa 2.9 million children under the age of five will die from malnutrition each year and for those that survive nutritional deficiency takes a toll on their immune system. It is likely that prolonged malnutrition will also significantly alter the microbiome.

The effect of diet on infectious disease & vaccination

1) Investigate how different diets impact the immune response against bacteria spread by contaminated food and water. 2) Examine the molecular and cellular effects that diet has on oral vaccinations.

The goals of this research project are

Pediatric non-alcoholic fatty liver disease clinical database & bio-bankNAFLD is not a well-understood disease, but the increasing rates of obesi-ty and incidence of NAFLD means we need to focus our efforts on trying to identify genetic and environmental factors that could contribute to this disease. Working with clinicians at Children’s Hospital LA we are initiating a NAFLD bio-repository, which will allow researchers to study the genetics, immunology and microbiome of children with this disease.

Cutting edge technologies & innovations

Organoids are three dimensional organs grown in a plate. They were named one of science’s greatest achievements in 2013.

The self-renewing nature of the intestinal epithelium makes it an ideal organ to grow in vitro. Our lab has begun isolating the stem cells necessary for these cultures and propagating them for use in a number of our projects.

The ability to use human stem cells allows us to test potential drug targets, biotherapeutic molecules and basic biological hypothesis without using animals.

Small intestinal & colonic organoid cultures

Day 0 Day 1

Day 4 Day 5

We are in an age of big data. There is practically an –omics for every-thing; Genomics, Proteomics, Metabolomics, Transcriptomics

to list just a few. While informative, all the data provided by these “-omics” is predictive. The data alone can not tell

us anything about the function of an identified bacte-ria, protein, metabolite or transcript in a living being. It is non-functional data. Our lab has begun to pair

these –omics with functional immunological as-says developed in our laboratory using human and mouse stool and its components. These

assays use the cells that associate with the stool in our intestine and use easy molecular

readouts to assign biological signatures.

Our hope is to eventually be able to use these assays to screen patients and identify when they are losing responsiveness to a drug or to predict

a flare-up in their disease.

Functional assays

Current ProgramsCommittee on microbiome-host interactions in disease (CMHID)§Bringing together art & science§

CMHID

Art & science

The mission of the Committee on Microbiome & Host Interactions in Disease (CMHID) is to advance both the science and the art of microbiome-related biomedical research as well as to foster unique collaboration and promote innovative

translational studies that will benefit patient treatment and care across the three USC campuses.

Microbiome-focused centers can be found at our nation’s most prestigious institutions and the number of NIH funded microbiome projects has increased 53% between 2010 and today indicating the growing importance of this ecological system. Currently there is no organized microbiome center at USC and while researchers here are working on microbiome or related disorders, they are working in isolation without a centralized community. The Committee on Microbiome & Host Interaction in Disease (CMHID) will change the face of microbiome research at USC by bringing together researchers and clinicians across nearly ten departments and three hospitals. A major goal of the CMHID is to accelerate discovery by providing affiliated researchers access to state-of-the-art instrumen-tation and technology.

For more information visit www.cmhid.org

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 crit-ical that the information regarding health, disease and the microbiome come from legitimate sources providing factual information.

We have established a relationship with the renowned USC School of Cinematic Arts and the Roski School of Fine Arts in order to develop programs that can educate local com-munities about health and the microbiome using art, film and writing. An emphasis of this initiative is to reach un-der-served populations regarding the importance of the mi-crobiome and nutrition and health.

As part part of our art & science initiative world-renowed bio-artist, Kathy High will be doing an artis-

it residency in DePaolo Lab during winter 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.

produced by Immaginomics Laba partnership between William DePaolo & Amy Parker

partners since chemistry 101, Bates College ‘99

coming together is a beginning; keeping together is progress; working together is success.

www.depaololab.com // twitter & instagram @depaololab // depaololab@gmail.com

-Henry Ford