R. Robert and Sally D. Funderburg Research Scholar Award in Gastric Biology Related to Cancer

2009 Funderburg Award Recipient

Mary Bronner, MD

Cleveland Clinic Foundation
Genomic Biomarkers of Gastric Cancer Risk in Intestinalized Helicobacter pylori Pangastritis

Receiving the Funderburg Research Scholar Award in Gastric Biology Related to Cancer makes a major impact on my research program’s continued efforts in gastric cancer.  We seek to unravel the role of genomic biomarkers in gastric tumorigenesis.  The stomach is one of many gastrointestinal organs subject to chronic inflammatory disease that predisposes a significant subset of ~10% of patients to cancer.  In the case of the stomach, of course, Helicobacter pylori (HP)-induced chronic intestinalized pangastritis is the background chronic inflammatory disease.  The disease is highly prevalent worldwide, as HP is the most common infection of mankind and gastric cancer is correspondingly one of the most common forms of cancer. We hypothesize that the chronic inflammatory injury from HP intestinalized gastritis damages the DNA of gastric epithelium and that this damage can be detected as a marker of increased cancer risk. The DNA damage markers we study include fluorescent in situ hybridization (FISH) to detect very early and even preclonal chromosomal gains and losses in individual cells, PCR assays of telomere length and telomerase activity, and anaphase bridge analysis to detect fused chromosome during cell division.  Our preliminary data indicate two very promising findings: 1) the genomic biomarkers are significantly more abnormal in the ~10% minority progressor patient subset who get cancer, relative to the majority of nonprogressors who don’t, and 2) they are detectable in single antral biopsies without any morphologic evidence of precancerous dysplasia.  These findings in particular are exciting for highly clinically significant reasons. Specifically, the major efforts and difficulties imposed by endoscopic cancer surveillance could be focused onto the minority subset of progressors who have abnormal genomic markers.  Furthermore, the large numbers of gastric biopsies needed to reliably detect the current gold standard precancerous biomarker, namely dysplasia, could be greatly reduced.  This follows directly from our finding that even single non-dysplastic antral biopsies appear to harbor earlier genomic changes.  Only with the continued support of research funding like the generous assistance of the Funderburg Research Scholar Award are we able to continue these pursuits, and for this we are grateful.

2008 Funderburg Award Recipient

Sheila Crowe, MD, AGAF

Associate Professor of Internal Medicine
University of Virginia

Role of AP Endonuclease-1/Redox Factor-1 in Regulation of the Gastric Epithelium:
Implications for Gastric Carcinogenesis

I am pleased to be the recipient of the AGA Foundation 2008 R. Robert & Sally D. Funderburg Research Scholar Award in Gastric Biology Related to Cancer. Much of my research career has been spent studying gastric mucosal inflammation associated with Helicobacter pylori, and its potential to cause significant diseases such as gastric cancer. We found that H. pylori induced gastric epithelial expression of IL-8 and that recruited phagocytes as well as bacteria were sources of reactive oxygen species, which contributed to enhanced programmed cell death in gastric epithelial cells. In collaboration with Dr. Sankar Mitra, an internationally known expert in DNA repair, we showed that infection and the associated oxidative stress increased gastric epithelial expression of a multifunctional, essential for life molecule, apurinic/apyrimidinic endonuclease (APE)-1, which is the rate limiting step in base excision DNA repair. Currently, our work focuses on understanding the transcriptional regulatory functions of APE-1, also known as redox factor (Ref)-1, and the roles APE-1/Ref-1 plays in regulating gastric epithelial function, growth and survival. The Funderburg award will play an important role in supporting our research that will establish how APE-1/Ref-1 modulates host responses to infection and the role it plays in gastric carcinogenesis. Support from the Funderburg award during the next two years is also critical for me to sustain and advance my research program while I compete for continued NIH R01 funding for our novel work. I am grateful to the AGA Foundation and the Funderburg family for the opportunity to advance our understanding of the development of gastric cancer and thereby, facilitate discoveries that could have implications for the prevention and treatment of gastric malignancy.

2007 Funderburg Award Recipient

Xiaolu Yang, PhD

Associate Professor,Department of Cancer Biology
Associate Investigator, Abramson Family Cancer Research Institute
University of Pennsylvania School of Medicine
Pennsylvania, PA

Role of MALT/paracaspase in normal lymphocytes and MALT lymphomas

I am very grateful to the AGA and its foundation for Digestive Health and Nutrition for selecting me as a recipient for the 2007 AGA Institute Funderburg Research Scholar Award. My lab has a longstanding interest in the molecular mechanisms of apoptosis and how they may relate to cancer and other human diseases. Recently, we are focusing on understanding the biology of mucosa-associated lymphoid tissue (MALT) lymphoma, the most common type of lymphoma that arises in extranodal tissue. MALT lymphomas affect virtually every organ in the human body, with the vast majority occurring in the stomach. The pathogenesis of MALT lymphomas is associated with independent chromosomal translocations, and the most frequent translocation generates a fusion protein between an apoptosis regulator (known as cIAP2) and a putative protease (known as MALT1). We found that cIAP2 normally inhibits the proliferation of lymphocytes. However, this function is missing in the fusion protein, contributing to the uncontrolled lymphocyte growth associated with MALT lymphomas. With the Funderburg Research Scholar Award, we plan to investigate the normal cellular function of MALT1 and how this function may be dysregulated in MALT lymphomas. We believe that our work will not only uncover the signal transduction governing lymphocyte proliferation but also better determine the molecular mechanisms of MALT lymphomas. Again, I wish to express my gratitude to AGA, its foundation, and the donor family for the honor bestowed on me. I hope that in my own way, I will contribute to the understanding and therapy of gastroenterological cancer.

2006 Funderburg Award Recipient

Steven Itzkowitz, MD, FACP, FACG

Mount Sinai School of Medicine

2005 Funderburg Award Recipient

JeanMarie Houghton,PhD

University of Massachusetts Medical School

2004 Funderburg Award Recipient

James R. Goldenring, MD, PhD

Vanderbilt University

2003 Funderburg Award Recipient

Lopa Mishra, MD

Georgetown University

2002 Funderberg Award Recipient

Steven F. Moss, MD

Brown University

2001 Funderburg Award Recipient

Debra Silberg, MD, PhD

University of Pennsylvania