The Biology of Colon Cancer Program (BCCP) encompasses an organ-systems and translational approach to understanding genetic and environmental factors that establish and maintain normal intestinal mucosal homeostasis and the perturbations that increase the probability for, and drive the development of, intestinal cancer. There are four overlapping themes, with many of the members investigating multiple themes: (I) the tumor microenvironment (inflammation, heterotypic cell interactions, and the intestinal microbiome), and its impact on genome integrity;(ii) maintenance of genomic integrity and the impact of nutrition and aging as major, interacting risk factors for sporadic colon cancer;(iii) intestinal cell maturation and stem cell biology;and (iv) altered metabolism as a marker of risk and driver of tumor development. The broad scientific goals of this program are to: first, understand how normal intestinal maturation and mucosal homeostasis are regulated by the integration of many different inter- and intracellular, and environmental, signals;and second, determine how failure in the integration of these systems compromises genomic integrity and mucosal homeostasis, thus elevating the probability of tumor development and progression. During the last funding period, the BCCP expanded from 11 to 18 members, recruiting both senior and junior faculty many already collaborating with members of the BCCP. Noteworthy additions to the previously existing work in the BCCP are new, interactive investigations on physiological, metabolic and molecular alterations in the intestinal mucosa with age and diet, major risk factors in the development of sporadic colon cancer. Furthermore, the membership of the BCCP will be now be consolidated on the Einstein campus to foster greater interaction with existing AECC programs, the Diabetes Center, the Nathan Shock Center for Aging, and the Stem Cell Institute, and to facilitate extension of the organ-systems approach of this program to other members of the Einstein research community. There are currently 19 members from 9 departments, of whom 15 are new to the program, supported by 12 NCI grants ($2.5M Direct) and 17 other peer reviewed cancer-relevant grants ($6.6M Direct). Since the last CCSG review there have been 339 cancer-relevant research papers by members of this program of which 19% represent intraprogrammatic, and 25% represent interprogrammatic publications.

Public Health Relevance

This program focuses on understanding the causes of cancers of the colon and rectum. The research benefits from the development of mouse models of human cancer by member of this group that facilitate studies that explore the impact of diet and nutrients in the development of these cancers. There is a particular interest in the roles of inflammation of the intestine, and the bacteria that live in the intestine, in causing these diseases. These results of these studies may inform new approaches to the prevention and treatment of colon and rectal cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA013330-41
Application #
8753326
Study Section
Subcommittee B - Comprehensiveness (NCI)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
41
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
City
Bronx
State
NY
Country
United States
Zip Code
10461
Ruiz, Penelope D; Gamble, Matthew J (2018) MacroH2A1 chromatin specification requires its docking domain and acetylation of H2B lysine 20. Nat Commun 9:5143
Van Arsdale, Anne R; Arend, Rebecca C; Cossio, Maria J et al. (2018) Insulin-like growth factor 2: a poor prognostic biomarker linked to racial disparity in women with uterine carcinosarcoma. Cancer Med 7:616-625
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Racine, Jeremy J; Stewart, Isabel; Ratiu, Jeremy et al. (2018) Improved Murine MHC-Deficient HLA Transgenic NOD Mouse Models for Type 1 Diabetes Therapy Development. Diabetes 67:923-935
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Kale, Abhijit; Ji, Zhejun; Kiparaki, Marianthi et al. (2018) Ribosomal Protein S12e Has a Distinct Function in Cell Competition. Dev Cell 44:42-55.e4
Mocholi, Enric; Dowling, Samuel D; Botbol, Yair et al. (2018) Autophagy Is a Tolerance-Avoidance Mechanism that Modulates TCR-Mediated Signaling and Cell Metabolism to Prevent Induction of T Cell Anergy. Cell Rep 24:1136-1150
Mao, Serena P H; Park, Minji; Cabrera, Ramon M et al. (2018) Loss of amphiregulin reduces myoepithelial cell coverage of mammary ducts and alters breast tumor growth. Breast Cancer Res 20:131

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