Faculty & Staff
Doctoral Training and Teaching Faculty
Timothy C. Wang, M.D.
Dorothy L. and Daniel H. Silberberg Professor of Medicine
Irving Cancer Research Center 9-925
1130 St. Nicholas Avenue
New York, NY 10032
Phone: 212 851 4581
1979 B.A., Williams College, Williamstown, Massachusetts
1983 M.D., Columbia College of Physicians and Surgeons, New York, New York
Dr. Wang’s research program is centered on understanding the role of inflammation and growth factors in the development of gastrointestinal cancers, with particular emphasis on Helicobacter-mediated gastric cancer. The research program encompasses five major funded projects: (1) Helicobacter pylori and gastric cancer. (2) Function and regulation of trefoil factor-2. (3) Regulation of histidine decarboxylase and histamine in the stomach. (4) The role of gastrin in colorectal cancer. (5) The origin of cancer stem cells.
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-deficient mice through targeted gene disruption, and to identify in vivo roles for incompletely processed gastrins such as glycine-extended gastrin (G-gly) and progastrin. With respect to colon cancer, his laboratory demonstrated a direct link between Wnt signaling and gastrin gene regulation, and between progastrin expression and an increased susceptibility to colon cancer in animal models. 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). He current serves on the International Steering Committee for Regulatory Peptides. Other areas of investigation include gastrin-regulated transcription, the regulation of protein stability and degradation, and the role of the trefoil peptide SP/TFF2 in gastric disease. His lab was the first to develop a knockout of the TFF2 gene, and more recently to show a role for TFF2 in innate immunity.
The major current focus of his laboratory is the nature of the association between inflammation and cancer. He was the first to show in vivo oncogenic roles for cyclin D1, able to induce neoplasia when overexpressed in mammary epithelium (Wang et al, Nature 1994). His laboratory has worked extensively with mouse models of Helicobacter infection, and was the first to describe a murine model of Helicobacter-dependent gastric carcinogenesis. Studies from Dr. Wang’s group has demonstrated the critical importance for Th1-mediated inflammation in the progression through atrophy/metaplasia and cancer in the mouse stomach, and he has also identified co-factor roles for hormones, nutrients and host factors in the development of cancer. However, the most exciting work currently underway in Dr.Wang’s laboratory relates to studies on the cellular origins of gastric cancer. Dr. Wang was the first to propose the hypothesis that epithelial cancers might possibly originate from a circulating stem cell. Studies were undertaken in Dr. Wang’s laboratory in 2001 that led to the remarkable observation that, in mice transplanted with GFP- or lacZ-tagged bone marrow and then infected with Helicobacter, gastric cancers originated not from gastric stem cells but from bone marrow-derived stem cells. Dr. Wang is the senior author of this paper, published in Science (Science 2004; 306:1568-71), and his lab is now highly focused on follow-up investigations related to this remarkable discovery. The landmark paper provides the first clear understanding of the link between inflammation and cancer, and in fact offers a new paradigm for the multistep model of cancer progression.
Recent Publications - Pubmed
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
Liang TJ, Reid AE, Xavier R, Cardiff RD, and Wang TC. (1996) Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors. J. Clin. Invest. 97:2872-7
Koh TJ, Goldenring JR, Ito S, Mashimo H, Kopin AS, Varro A, Dockray GJ, and Wang TC. (1997) Gastrin knockout mice show altered gastric differentiation and decreased colonic proliferation. Gastroenterology 113:1015-25
Koh TJ, Dockary GJ, Varro A, Cahill RJ, Dangler CA, Fox JG, and Wang TC. (1999) Overexpression of glycine-extended gastrin in transgenic mice results in increased colonic proliferation. J. Clin. Invest. 103:1119-26
Wang TC, Dangler C, Chen C, Goldenring JR, Koh TJ, Raychowdhury R, Coffey RJ, Ito S, Varro A, and Fox JG. (2000) Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric carcinoma. Gastroenterology 118:36-47
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 6:536-542