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Landon Foundation–AACR INNOVATOR Award for Cancer Prevention Research

The Landon Foundation-AACR INNOVATOR Award for Cancer Prevention Research was established to recognize the outstanding achievement of a junior faculty-level scientist working in the field of cancer prevention. The goals of the program are to encourage younger investigators to pursue cancer prevention research of significant scientific merit; provide the support necessary to sustain and enhance highly meritorious cancer prevention research; foster interaction between and among cancer scientists and disseminate the scientific knowledge about cancer prevention research; and contribute to a global impact against cancer. The research proposed for funding may be basic, translational, clinical, or epidemiological in nature and can be in any discipline of cancer prevention research.

2​015 Grantee

Rong Xu, PhD  
Assistant Professor of Medical Informatics
Case Western Reserve University
Cleveland, Ohio

  Uncovering links between microbiome metabolites and colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. CRC susceptibility and progression are primarily driven by gene–environment interactions. Human gut microbiota (>1014 microbial cells comprising about 500-1000 different species) are important modifiable environmental factors that we are exposed to continuously. These microbiota exist in a symbiotic relationship with a human host by metabolizing compounds that humans are unable to utilize and by controlling the immune balance of the human body. Gut microbiota and its metabolites are increasingly recognized as important environmental factors influencing colon carcinogenesis not only via the pro-carcinogenic inflammatory activities of specific pathogens but also via the cumulative effects of microbial metabolites of the resident gut microbiota. Although the link between human gut microbial metabolism and colon carcinogenesis has been recognized, systematic evaluation of gut microbial metabolites and the interacting genetic pathways in relation to CRC is lacking. Dr. Xu proposes to develop innovative computational approaches to integrate and analyze vast amounts of heterogeneous and complex biomedical data towards deciphering the interplay between host genetics, microbes, and CRC carcinogenesis. The identification of microbial metabolites and the understanding of their role as key mediators through which these bacteria promote/protect against CRC will greatly facilitate our understanding of the complex host genome-microbiome interaction in colon carcinogenesis and enable/activate new possibilities for its diagnosis, prevention, and treatment.

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2014 Grantee

Tamas Gonda, MDTamas Gonda, MD  
Assistant Professor, Department of Medicine
Columbia University Medical Center
New York, New York

Epigenetic Targeting of the Microenvironment in Gastric Chemoprevention

Dr. Gonda’s main research interest is in the field of gastrointestinal chemoprevention. In prior works he has focused on epigenetic changes, mainly DNA methylation, as a modifiable target of chemoprevention. In animal models he has studied the effect of both methyl donor supplementation and demethylating agents and their effect on gastric and pancreatic carcinogenesis. The current proposal expands on these observations to evaluate the role and epigenetic mechanisms of folate based methyl donor supplementation in transgenic and chemical models of gastric carcinogenesis. As epigenetic alterations are particularly significant in the tumor microenvironment a secondary aim of this proposal is to investigate the role of targeting DNA methylation in these cells as a way to prevent development of carcinoma. Two cell populations are examined closely: cancer associated fibroblasts and tumor infiltrating immune cells. An important goal will be to evaluate the way these populations of cells may be targeted to synergize with methyl donor supplementation. The results of these studies may have direct effect on clinical studies. The animal models used recapitulate most features of gastric carcinogenesis and many of the intervention strategies tested can be adopted in human trials. 

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