Biology of Colon Cancer

PROJECT SUMMARY (See Instructions): 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.