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
Willis, Ian M; Moir, Robyn D; Hernandez, Nouria (2018) Metabolic programming a lean phenotype by deregulation of RNA polymerase III. Proc Natl Acad Sci U S A 115:12182-12187
Hayama, Ryo; Sparks, Samuel; Hecht, Lee M et al. (2018) Thermodynamic characterization of the multivalent interactions underlying rapid and selective translocation through the nuclear pore complex. J Biol Chem 293:4555-4563
Martynova, Elena; Bouchard, Maxime; Musil, Linda S et al. (2018) Identification of Novel Gata3 Distal Enhancers Active in Mouse Embryonic Lens. Dev Dyn 247:1186-1198
Huang, Kezhen; Mukherjee, Subhajit; DesMarais, Vera et al. (2018) Targeting the PXR-TLR4 signaling pathway to reduce intestinal inflammation in an experimental model of necrotizing enterocolitis. Pediatr Res 83:1031-1040
Bines, Jose; Tevaarwerk, Amye J (2018) Baby steps: Pregnancy outcomes after human epidermal growth factor receptor 2-targeted therapy. Cancer :
Mathew, Deepti; Wang, Yanhua; Van Arsdale, Anne et al. (2018) Expression of ?V-Tubulin in Secretory Cells of the Fallopian Tube Epithelium Marks Cellular Atypia. Int J Gynecol Cancer 28:363-370
Mao, Kai; Quipildor, Gabriela Farias; Tabrizian, Tahmineh et al. (2018) Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice. Nat Commun 9:2394
Entenberg, David; Voiculescu, Sonia; Guo, Peng et al. (2018) A permanent window for the murine lung enables high-resolution imaging of cancer metastasis. Nat Methods 15:73-80
Iqbal, Niloy Jafar; Lu, Zhonglei; Liu, Shun Mei et al. (2018) Cyclin-dependent kinase 4 is a preclinical target for diet-induced obesity. JCI Insight 3:
Sharma, Yogeshwar; Liu, Jinghua; Kristian, Kathleen E et al. (2018) In Atp7b-/- Mice Modeling Wilson's Disease Liver Repopulation with Bone Marrowderived Myofibroblasts or Inflammatory Cells and not Hepatocytes is Deleterious. Gene Expr :

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