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Research Summary
Dr. Wang’s research program is centered on understanding the role of chronic inflammation in modulating stem cells and the tissue microenvironment in ways that predispose to gastrointestinal cancers. The lab has been an international leader in models of Helicobacter-mediated gastric cancer but has also developed inflammatory models of colorectal, esophageal and pancreatic neoplasia. The lab is part of the NCI-sponsored Tumor Microenvironment Network (TMEN), and has investigated roles for cancer-associated fibroblasts (CAFs) and myeloid-derived suppressor cells (MDSCs) in carcinogenesis. Finally, the laboratory is deeply engaged in studies of stem cells, including bone marrow-derived stem cells and resident tissue stem cells in the gastrointestinal tract, and the events that can lead to conversion to cancer stem cells.
Research Activities
The major current focus of his laboratory is the nature of the association between inflammation and carcinogenesis, and in particular the role of chronic inflammation in the initiation of gastrointestinal cancer. His groups was one of the first to demonstrate roles for bone marrow-derived stem cells (BMDC’s) in contributing to gastric cancer (Science 2004), and his group has continued to explore roles for BMDC’s as precursors of cancer-associated fibroblasts, myeloid derived suppressor cells and also dysplastic epithelial cells. Dr. Wang leads a team of U54-funded investigators and the Tumor Microenvironment program at Columbia that are exploring broadly the role of the tumor microenvironment in promoting the growth of both gastric and liver cancer. Dr. Wang’s laboratory was the first to show that overexpression of a single proinflammatory cytokine (IL-1beta) can induce cancer in a mouse (Cancer Cell 2008). Chronic inflammation leads to an expansion of resident tissue stem cells in the gastrointestinal tract, and Dr. Wang’s laboratory has identified several markers for both quiescent stem cells and progenitor cells and is actively performing Cre-mediated lineage tracing studies to elucidate the early events in carcinogenesis. In addition, Dr. Wang’s laboratory has active murine models and projects related to the role of chronic inflammation in promoting colorectal cancer, esophageal cancer, and pancreatic cancer. Dr. Wang began his research career in the area of gastrin biology, and his research has continued to explore the role of gastrin peptides in diverse diseases including peptic ulcer disease, gastric cancer, and colorectal cancer. His laboratory was the first to generate gastrin knockout mice and to demonstrate using transgenic technology in vivo roles for progastrin. Most recently, he has demonstrated a role for progastrin and the gastrin receptor in modulating colonic stem cell symmetric division (J. Clin. Invest. 2009). He has been a leader in the field of gastrin biology, and his work in the field of gut hormones has included organizing the International Conference on Gastrin (1999) and the International Regulatory Peptide Conference (2002).
Positions & Appointments
| present |
Dorothy L. and Daniel H. Silberberg Professor of Medicine |
Columbia University, College of Physicians & Surgeons |
New York, NY |
| present |
Chief, Division of Digestive and Liver Diseases |
Columbia University, College of Physicians & Surgeons |
New York, NY |
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Education and Training
| 1979 |
B.A. |
Williams College, Williamstown, MA |
| 1983 |
M.D. |
Columbia University, College of Physicians & Surgeons, New York, NY |
| 1983-1986 |
Intern and Resident in Internal Medicine |
Barnes Hospital, Washington University School of Medicine, St. Louis, MO |
| 1986-1989 |
Research Fellow in Medicine |
Harvard Medical School, Boston, MA |
| 1986-1989 |
Clinical and Research Fellow in Medicine |
Massachusetts General Hospital, Boston, MA |
Selected Publications:
1. Wang TC, Cardiff RD, Zuckerberg L, Lees E, Arnold A, and Schmidt EV. (1994) Mammary hyperplasia and carcinoma in MMTV-Cyclin D1 transgenic mice. Nature
369:669-71
2. Fox JG, Beck P, Dangler CA, Whary MT, Wang TC, Shi HN, and Anderson CN. (2000) Concurrent enteric helminth infection modulates inflammation, gastric immune responses, and reduces Helicobacter-induced gastric atrophy. Nature Medicine
6:536-42
3. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC. (2004) Gastric cancer originating from bone marrow-derived cells. Science
306:1568-71
4. Tu S, Bhagat G, Cui G, Takaishi S, Kurt-Jones EA, Rickman B, Betz KS, Penz-Oesterreicher M, Bjorkdahl O, Fox JG, Wang TC. (2008) Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell
14:408-19
5. Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, Gordon SA, Shimada Y, Wang TC.
(2009) Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells
27:1006-20
6. Jin G, Ramanathan V, Baik GH, Wang SSW, Tu S, Pritchard DM, Varro A, Shulkes A, Wang TC. (2009 ) Inactivation of the cholecystokinin-2 receptor inhibits progastrin-dependent crypt fission, colonic proliferation and colorectal cancer. Journal of Clinical Investigation
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