Faculty members in the Section of Gastroenterology, Hepatology and Nutrition are currently involved in a number of basic and clinical research investigations on many different diseases and disorders. Below is a list of the research and clinical research faculty members and their interests.

MARC BISSONNETTE, M.D.
Associate Professor of Medicine
My research interests include investigations of how the cells in the colon develop into colon cancers. I am interested in both genetic and environmental factors that contribute to tumor development. I am researching how “growth factors” and their receptors are regulated by diet and genetics and control intestinal cell function and proliferation (growth). We are studying changes in growth factor signals that occur early in sporadic colon cancer in human aberrant crypt foci, microscopic precursors of colon cancer. We would like to understand how diet and genetics control growth signals that drive the development of aberrant crypts.

Diet is an important environmental risk factor for colon cancer development, especially Western style diets high in animal fat and red meat. Bile acids from the liver are believed to contribute to diet-related increased risk of colon cancer. Our laboratory is studying how bile acids contribute to the promotion of colon cancer. In animal models the primary bile acid cholic acid potently enhances colon cancer development. Another bile acid, ursodeoxycholic acid that is used in several forms of liver disease has been shown to decrease the risk of ulcerative colitis-associated colon cancer. We are studying how cholic acid promotes tumorigenesis, while ursodeoxycholic acid inhibits tumor development.

A third area of interest in our laboratory is the role of inflammation in colon cancer development. Ulcerative colitis, a chronic inflammatory disease of the colon, is an important risk factor for colon cancer. We are studying changes in gene expression that drive this malignant transformation. We have identified individuals with long standing ulcerative colitis. Some of these individuals have early stages of tumor development, whereas others do not. We are determining whether there is a “Signature” of unique changes in genes that are turned on or turned off (disease specific patterns of gene expression) that could distinguish relative risk of colon cancer development. Such findings could allow us to focus on more effective surveillance for those at higher risk.

DAVID BOONE, PH.D.
Assistant Professor of Medicine
My research is focused on understanding the regulation of inflammation in the gut. I am particularly interested in the way bacteria and other germs activate the inflammation that damages the intestine in Crohn’s disease and ulcerative colitis. In order to study the role of individual genes involved in inflammation, my laboratory makes “knockout mice” that each lack one specific gene of interest. This approach allows us to decipher what the role of a single gene is by examining what happens when that gene is absent. There are many examples of knockout mice that develop inflammatory bowel disease and each one teaches us something new about how inflammation is regulated in the gut. Our recent work has identified an entirely new mechanism for the activation and regulation of inflammation in the gut by a process called ubiquitination. We are currently making new knockout mice that have defects in the regulation of ubiquitination in order to fully understand this process. This research may lead to new classes of drugs that target ubiquitination and treat inflammatory bowel diseases.

RICHARD BREUER, M.D.
Clinical Associate of Medicine
I have returned to the University of Chicago GI clinic after many years of General GI in another setting. My primary role at the University of Chicago is to mentor the Fellows in their Continuity Clinics.

EUGENE B. CHANG, M.D.
Martin Boyer Professor of Medicine
Associate Director for Academic Programs and Training in Gastroenterology
Director: The Martin Boyer Laboratories
The intestinal mucosa, or the lining cells of the intestine, is largely responsible for the absorption of fluid, nutrients, and electrolytes and for preventing the entry of noxious or harmful agents into the blood stream. In inflammatory bowel diseases, the mucosa is a primary site of injury, resulting in malabsorption, diarrhea, malnutrition, and sepsis (when bacteria enter the blood stream). Our laboratory has been particularly interested in understanding how chronic inflammation causes mucosal injury and dysfunction and how inherent cellular mechanisms can be evoked to protect the mucosa against catastrophic injury. With respect to the latter, we have been studying the role of intestinal heat shock proteins, molecules present in all living cells, that can be rapidly induced improve intestinal survival even under adverse conditions. We have identified a number of molecular pathways for the regulation of heat shock protein gene expression which are unique to the intestinal mucosa. These pathways are stimulated by a number of IBD treatments, accounting in part for their therapeutic efficacy. By identifying therapeutic agents that can enhance heat shock protein expression and cellular protection, we will be able to limit the extent and severity of mucosal injury associated with Crohn’s Disease or Ulcerative Colitis.

More recently, the lab has been engaged in studies of host-microbial interaction. These investigations led to discovery of two important pathways of host defense. The first involves a protein encoded by a gene located in a region of linkage disequilibrium that appears to be contribute to increased risk of Crohn’s disease. The second involves a unique family of proteins that can block the attachment and invasion of intestinal pathogens such as Salmonella – a major cause of food poisoning and diarrheal disease. Finally, we have developed a new core laboratory capable of studying the microbes in the colonic lumen which are now known to play a major role in the development of IBD. The analysis involves the application of computational science (bioinformatics) to define and identify bacterial species of the gut through their molecular signatures. This approach is currently being used by numerous clinical and basic research investigators to normal physiology, IBD, necrotizing enterocolitis and pouchitis.

RUSSELL D. COHEN, M.D., FACG, AGAF
Associate Professor of Medicine
My research interests are primarily involved in two major areas of clinical gastroenterology: inflammatory bowel diseases and health care outcomes. We have been studying both standard and experimental pharmacological therapies, including novel immune modulating agents, as they affect outcomes such as “quality of life” and the economics involved in the diagnosis and treatment of Inflammatory Bowel Disease. These interests in health care outcomes have led to a working relationship with the faculties of the University of Chicago’s Department of Health Studies. By applying the principles of biostatistics, epidemiology, and other integral components of health outcomes research, I hope to address some of the perplexing issues arising in the field of gastroenterology in the face of a rapidly changing health care system.

CHARLES E. DYE, M.D.
Assistant Professor of Medicine
My specialty is interventional endoscopy with a focus on Endoscopic Ultrasound, Pancreaticobiliary diseases, and endoscopic therapy of gastrointestinal malignancies. These areas are rapidly expanding under the direction of Dr. Irving Waxman. I have published experience with: 1) novel techniques for diagnosing and treating small bowel conditions and for patients requiring pancreatic and bile duct therapy after surgical alteration of anatomy; 2) expanding role of endoscopic ultrasound experience for diagnosis and management of dysplasia and cancer; and 3) guiding evolving protocol for more minimally invasive diagnosis and mediastinal staging of lung cancer with the assistance of endoscopic ultrasound.

NATHAN A. ELLIS, PH.D.
Associate Professor of Medicine
The main research focus of the Ellis laboratory is the study of genomic instability and its relationship to cancer susceptibility. This focus includes the study of both high-penetrance and low-penetrance cancer-causing genes, population genetics of human cancer susceptibility alleles, and the molecular and cellular biology of the cancer susceptibility genes themselves.

A particularly potent and interesting model of cancer susceptibility is provided through the study of a rare human genetic disorder referred to as Bloom’s syndrome (BS). In BS, persons have a deficiency of a DNA unwinding protein, the BLM helicase, which deficiency exposes the cells to excessive recombination and the accumulation of genetic mutations. In our recent studies of the BLM protein, we have shown that the localization of BLM in the nucleus is regulated by modification of BLM by the protein SUMO (small ubiquitin-like modifier). When DNA is damaged, for example, by treatment with DNA-damaging agents, BLM moves from nuclear storage reserves to the sites of damage where it helps to recruit other DNA repair proteins to the damage sites. SUMO modification controls this recruitment process, at least in part by regulation of the amount of BLM in damage versus storage sites. When cells fail to regulate BLM localization properly, they are sensitized to DNA damage, and preliminary evidence suggests they accumulate chromosome mutations. Currently, we are determining how SUMO controls BLM localization.

In addition to this work, we recently published in the journal Human Mutation a five-year study of all the detectable BLM mutations in 134 persons with BS. This study showed that most persons with BS inherit at least one of their BLM mutations identical-by-descent from a founder individual. The profile of mutations in BS reveals genetic forces in human populations that persistently and pervasively generate founder mutations.

Our studies of the BLM gene have also pointed to the role of mutations in DNA repair genes in susceptibility to the development of colorectal cancer (CRC). Persons who carry a mono-allelic BLM mutation (heterozygotes for BLM mutation) have a two-fold increase in the risk of developing CRC. Knowing this, we set out to investigate the role of mutations in other DNA repair factors in CRC. We have used high throughput screening methods to identify novel DNA changes in genetic components of the base-excision repair pathway. Many novel DNA changes have been found and we are now genotyping these changes in CRC cases and comparing the frequencies of these changes in cases versus controls. We have also initiated two important protocols—one retrospective and the other prospective—to study DNA changes that might increase CRC-susceptibility in the African American population.

With expertise in the modern technologies available to genotype DNA changes that may be associated with disease, we are developing a Genetics Core Facility for the Digestive Diseases Research Core Center that will assist members of the Section in functional and genetic studies of DNA changes that increase the risk of developing inflammatory bowel diseases.

IRA HANAN, M.D.
Associate Professor of Medicine
The rewards of practicing at a leading Academic Hospital and Top ranked program in Gastroenterology offer me the opportunity to practice at the highest level of knowledge and technology that provides my patients with the comprehensive approaches to simple and complicated GI disorders. My roles include Directing the Out-Patient GI Clinic and Clinical Teaching of our GI Fellows, Medical Residents and Students.

STEPHEN B. HANAUER, M.D.
(GIRF, in honor of Joseph B. Kirsner) Professor of Medicine and Clinical Pharmacology
Chief, Section of Gastroenterology and Nutrition
In addition to a large clinical practice, our group continues to perform extensive clinical research regarding the epidemiology, natural history and medical therapy for inflammatory bowel disease. Based upon the GIRF Women’s Board sponsorship of the IBD registry (presently over five thousand patients with inflammatory bowel disease) we have explored the familial and genetic aspects of IBD, environmental contributors (e.g., smoking) and cancer surveillance. We have established guidelines for clinical trials in ulcerative colitis and Crohn’s disease and have been at the forefront of developing clinical protocols and evaluating novel medical therapies for a spectrum of IBD scenario. These studies have led to the FDA approval of Rowasa enemas, Asacol, Pentasa, Dipentum, Entocort and Remicade. We continue to study over ten new compounds and therapies for ulcerative colitis and Crohn’s disease. Continued efforts are underway to optimize and select therapies for individual patients and disease groups. We are cooperating with the genetics group to further classify and correlate genetic patterns and clinical disease characteristics.

Clinical Research: Inflammatory Bowel Disease Registry: Designed and maintains 6000 patient data-base.

LAURA E. HARRELL, M.D.
Assistant Professor of Medicine
My primary research interests involve applying bench-side research (basic sciences) to clinical care. Recently my efforts have been focused on examining the role of the enteric bacterial community in health and disease, with a particular focus in the inflammatory bowel diseases. I have been involved in the development of the 16S Core Facility, which is part of the Digestive Diseases Research Core Center (a NIH supported program). This core center provides the comprehensive preparation of tissue and stool samples for 16S genotyping, DNA sequencing and capillary electropheresis with bioinformatics support. The GIRF Associate’s Board is funding one of our studies examining the effect of bowel preparation on the enteric bowel community utilizing this technology and the core center services. I am also currently collaborating with Dr. Vincent Young at Michigan State University; an expert in microbial ecology, in a NIH funded study examining the role of the enteric microbiota in post-operative recurrence in patients with Crohn’s disease.

HEIDI HUCK, M.D.
Clinical Associate (Assistant Professor)
I am actively involved with the University of Chicago GI Fellowship training program. At the University campus, I contribute to the endoscopic training of GI fellows at all levels. My focus is on the initial acquisition and refinement of endoscopic skills for colonoscopy and upper endoscopy. At Weiss Memorial Hospital, I am co-director with Dr. Uzer of the University of Chicago Fellowship rotation emphasizing general gastroenterology and hepatology in a community-based hospital.

I am pursuing a Masters degree in Biomedical Visualization at the University of Illinois, Chicago campus - one of only four such programs in the country. My research interests include visual translation of medical information for research needs, medical education and patient information.

DONALD M. JENSEN, M.D.
Professor of Medicine
Director, Center for Liver Disease
Our main research focus is in the development and testing of newer and more effective therapies for the treatment of hepatitis C. During the past year, we have presented and published a paper describing a new paradigm for the use of peginterferon and ribavirin in the treatment of the most difficult-to-treat population of hepatitis C patients (genotype 1). Dr Jensen is also the lead investigator on an international study designed to treat prior peginterferon/ribavirin nonresponder patients. We are currently testing several new treatments for hepatitis C including: a novel therapeutic vaccine; a new HCV protease inhibitor (VX-950), and a new HCV polymerase inhibitor. These exciting new treatments will revolutionize the treatment of this important disease.

KAREN E. KIM, M.D.
Associate Professor of Medicine
Associate Investigator, University of Chicago Cancer Research Center
Faculty Affiliate, Center for the Study of Race, Culture and Politics
My interests are centered on health disparities and community based participatory research in two distinct areas. I have been an active public health advocate for reducing cancer disparities in Asian Americans. My research in hepatitis B in Asian Americans has focused on disaggregating Asian subgroups and studying the different and unique barriers to liver cancer prevention and treatment in these populations. I also study disparities in colorectal cancer prevention in minorities, with an emphasis on culturally competent educational interventions, which positively impact behavioral changes for colorectal cancer screening. In addition, I am serving as the co-founder and chair of the newly established Asian Cancer Prevention Organization. My other area of interest is in understanding educational methods for cultural competency training. As a member/trainer of the Center for Cross Cultural Education, I am involved in developing measures to understand the impact of cultural competency on patient care.

JOSEPH B. KIRSNER, M.D.
Louis Block Distinguished Service Professor of Medicine
Nearing the age of 98, I continue to be involved in the activities of the Gastroenterology Section at the University of Chicago Medical Center. I continue to have conversations on IBD with the following: UCB Pharmaceutical representatives; Dr. Mark Leifer; and Chicago Cancer Research Foundation preceptors. I continue to consult frequently with organizations and patients for advice regarding clinical and scientific issues in Gastroenterology. Although I do not see patients officially, I frequently talk with patients who call me. My office continues annually to refer patients to physicians at the University of Chicago and also to physicians locally, nationally and internationally. I continue with the development of my life history (Dr. Joe; An American Gastroenterologist) and my impact on the development of the University of Chicago Medical Center and the development of Gastroenterology and Internal Medicine in the United States with Dr. James Franklin.

I gave a talk on April 3, 2007 on personal events in World War II. I am scheduled to talk to the University of Chicago Alumni on June 1, 2007 on the history of the University of Chicago Medical Center. I am currently developing a talk on the nature of research in Gastroenterology and why discoveries happen.

YAN CHUN LI, PH.D.
Associate Professor of Medicine
Our research focuses on the vitamin D endocrine system. We are particularly interested in the physiological and pathological functions of the vitamin D receptor (VDR) in the gastrointestinal tract, the kidney, the cardiovascular system, as well as in lipid metabolism and adipogenesis. With regard to the GI tract, we have been exploring the chemopreventive property of the VDR in colon cancer development as well as the protective role of the VDR in inflammatory bowel disease (IBD). We have found that VDR interacts with the APC/b-catenin pathway in the regulation of intestinal tumor formation. We have also demonstrated that VDR plays a critical role in the maintenance of intestinal epithelial barrier integrity, and VDR-deficiency drastically increases the susceptibility of intestinal mucosal injury and the risk of IBD development. Our data will lead to more investigations to explore the pharmaceutical potentials of vitamin D analogues in prevention and treatment of colon cancer and IBD.

SMRUTI R. MOHANTY, M.D, MS.
Assistant Professor of Medicine
My research interest includes long-term outcomes of patients with chronic viral hepatitis B & C with/without HIV co-infection and liver transplantation. I am also involved in developing different management strategies for the prevention and treatment of viral hepatitis and recurrent hepatitis in patients who get liver transplantation. Furthermore, I am continuing studying the natural history, racial variations of fatty liver disease and patients with hepatocellular carcinoma (HCC).

GAUTHAM REDDY, M.D.
Assistant Professor of Medicine
Our liver group remains active in several clinical research studies exploring various therapeutic agents for viral hepatitis. In the past year, I have received a grant from the GIRF Associates' Board to explore a novel approach to enhancing standard therapy for hepatitis C with a class of medications used to treat high cholesterol. Additionally, we will soon be studying a new medication for the treatment of hyponatremia which is a severe complication of the advanced liver disease. I am very active in our hepatology division as we have rapidly expanded our liver transplantation services. My clinical practice also includes general gastroenterology and inflammatory bowel disease. I am also involved in the training of GI fellows, residents and medical students.

NANCY REAU, M.D.
Assistant Professor of Medicine
I am working with the ALF and several Chicago Universities to develop a free Hepatitis B Clinic, starting with the underserved china town population. My other research interests focus on NAFLD and developing therapies, improving Hepatitis B awareness and education, and Hepatitis C treatment.

B.H. GERALD ROGERS, M.D.
Clinical Professor of Medicine
I received FDA approval for an open label “Pilot-study of oral 852A for elimination of high-grade dysplasia in Barrett’s esophagus” (www.clinicaltrials.gov/ct/show/NCT00386594). This study uses an immune stimulating drug which is now designated 852A. The study medication works by stimulating the innate immune system to produce interferon alpha which then helps the body reject early cancer cells. The beauty of this treatment is the medication would simply given by mouth. There is already a similar dermatologic medication on the market that successfully eliminates actinic keratosis, a pre-malignant lesion of the skin. Unfortunately, this study is presently on hold because of inability to obtain the drug. As soon as the drug becomes available I will be able to enroll patients into the protocol.

DAVID T. RUBIN, M.D.
Associate Professor of Medicine
Program Director, Fellowship in Gastroenterology, Hepatology and Nutrition
Co-Director, Inflammatory Bowel Disease Center
Associate Faculty, MacLean Center for Clinical Medical Ethics
Associate Investigator, University of Chicago Cancer Research Center
My research continues to focus on advanced technologies for screening and diagnosis in inflammatory bowel disease and prevention of colorectal cancer. In the last year, my research team has accomplished a tremendous amount of exciting work. Collaborating with the Department of Pathology at the University of Chicago, we developed a novel grading scale to quantify the degree of large bowel inflammation in patients with ulcerative colitis. In subsequent studies, we found that the degree of inflammation to be a predictor for the development of colitis-related bowel cancer. This suggests that better control of the inflammatory process in ulcerative colitis may reduce the risk of colon cancer in these patients. Our next step is to investigate whether our novel scale, which determines inflammation at the microscopic level, correlates to inflammation markers in the blood, inflammation activity seen during colonoscopy, and disease activity determined by patients’ symptoms. We will also be among the first researchers in the world to use a new imaging technology, optical coherence tomography, to study the role of inflammation in ulcerative colitis. Much of this work is possible due to the generous funding from the GIRF Associates’ Board. Additionally, my group continues to study wireless capsule endoscopy ("the pill camera") for use in inflammatory bowel disease, and we are collaborating with the Department of Radiology for work in CT colonography (virtual colonoscopy).

CAROL SEMRAD, M.D.
Associate Professor of Medicine
My interests are in small bowel diseases and nutrition in particular celiac disease, the short bowel syndrome and obscure GI bleeding. I have written chapters on diarrhea and malabsorption for the Cecil and Kelly Textbooks of Medicine and developed teaching slides on nutrition and the short bowel syndrome for the American Gastroenterological Association. I am a co-investigator on a research study on the pathogenic mechanisms of intestinal injury in celiac disease.

To improve diagnosis and treatment of small bowel diseases, I learned new endoscopic technologies including Video Capsule Endoscopy and Double Balloon Enteroscopy. Based on this work, the University of Chicago has the largest experience in the country in the diagnosis and management of small intestinal bleeding and ulcerating diseases. We serve as a teaching center for other gastroenterologists in Double Balloon Enteroscopy.

HELEN TE, M.D.
Assistant Professor of Medicine
As our hepatology and liver transplant program grew and expanded, we increased our involvement in many clinical trials using novel therapeutic agents in the drive to eradicate chronic hepatitis C. We continue to face the challenge of individuals who fail conventional therapy for these diseases, and our current clinical trials give us the first glimpse at promising new and more effective medications which may provide us with the solution to this growing problem in the near future. We continue to face the challenge of specific difficult to treat populations with this disease, such as patients with renal failure who are on dialysis, and we recently published our experience on the lack of efficacy of conventional therapeutic agents in this population.

I am also interested in prevention and treatment of recurrent hepatitis C following liver transplantation, and in the fine-tuning of immunosuppression in liver transplant recipients to decrease the side-effects while preserving graft function. I am currently evaluating a new laboratory assay as a guide to individually minimize the immunosuppressive drugs in long-term liver transplant recipients without increasing the risk for graft rejection.

MICHAEL UZER, M.D.
Clinical Associate, Assistant Professor
I continue to train the U. of C. GI Fellows in both upper and lower endoscopy at the University of Chicago Procedure Unit, and in Clinical Consultation, Endoscopy and Endoscopic Retrograde Cholangiopancreatography at Weiss Hospital.

IRVING WAXMAN, M.D.
Professor of Medicine
Professor of Surgery
Professor of the Cancer Research Center
Associate Director of the University of Chicago Center for Gastrointestinal (GI) Oncology
Director of Endoscopy
My primary interests relate to the area of Gastrointestinal Oncology and early detection of gastrointestinal cancer with endoscopy. Our new program will be focused in three areas, Interventional Endoscopic Ultrasound, Early Endoscopic cancer detection with chromoendoscopy (utilizing different dyes to find abnormalities of the lining of the GI tract) and High magnification and High resolution endoscopes and Endoscopic surgery, looking at minimally invasive ways to remove early cancers with an endoscope and avoiding surgery.

For this academic year we received two grants from the ASGE and the ACG. The first grant (40K) “EUS-guided fine needle tissue acquisition using high negative pressure suction versus standard EUS-guided fine needle aspiration for the diagnosis of solid lesions of the gastrointestinal tract and of adjacent organs: a multicenter prospective cross-over study” looks at better and more efficient ways of obtaining a tissue (biopsy) diagnosis with endoscopic ultrasound in pt’s with Cancer. The second grant (120K) is a mulitcenter study looking at chromoendoscopy (using dyes during colonoscopy) to identify earlier colon precancerous and cancerous changes.

We are also fortunate in having Dr Alberto Herreros-Tejada from Madrid, Spain who will be spending a year working with us doing research in endoscopic ultrasound. Dr Herreros received an ASGE international grant in order to be with us at University of Chicago.

As in previous years the interventional program at U of C continues to thrive and grow as we enter our 6th year. Our volume of interventional procedures continues to grow leading to expansion of the interventional suites by adding a second Endoscopic Ultrasound room and an additional room with fluoroscopic (x-rays for endoscopic procedures) capabilities. Finally, we welcome the newest member of our team, our PA Barbara Cislo who brings endless energy to our day to day operations

CHARLES S. WINANS, M.D.
Sara & Harold Lincoln Thomas Professor of Medicine
I maintain a general clinical gastroenterology practice with special interests in diseases of the esophagus. Major research interests include studies of the physiology of the normal human esophagus, pathophysiology of gastro-esophageal reflux, and controlled clinical trials of new treatments of gastrointestinal diseases.