Colorectal and Gastric Cancers

Current Projects
Jason M. Sheltzer, PhD

Dr. Sheltzer studies how aneuploidy, or having too many or too few chromosomes in the cell, affects cancer development and treatment. Approximately 55% of breast cancers have an extra copy of one part (called the “q arm”) of chromosome 1. His lab is developing cutting-edge chromosome engineering technology to eliminate the extra copies of 1q from breast cancer cell lines and determine whether this prevents the cells from forming tumors. Additionally, they will test whether aneuploidy causes ovarian cancer cells to be sensitive to any chemotherapies, with the goal of identifying a drug that specifically kills cells with extra copies of chromosome 1q without affecting normal cells. These experiments could lead to highly effective “chromosome-specific” therapies based on aneuploidy.

Project title: “Are cancers addicted to aneuploidy?”
Institution: Cold Spring Harbor Laboratory
Award Program: Innovator
Cancer Type: Gynecological, Colorectal, Sarcoma, All Cancers
Research Area: Chromosome and Telomere Biology
Harshabad Singh, MBBS

Cancers involving the lower esophagus (esophageal adenocarcinomas) have dramatically increased in number over the last several decades. The reason for rise in this cancer is not completely understood. However, long before these esophageal cancers arise the normal esophageal multilayered squamous lining (or epithelium) is replaced by a single layered columnar epithelium which has features similar to the lining of the intestine and is known as Barrett’s esophagus. Dr. Singh proposes to investigate the origins and factors governing the genesis of Barrett's esophagus and understand its specific vulnerability to progress to cancer. This work will yield insights into disease mechanisms and reveal novel preventive strategies for esophageal adenocarcinomas.

Project title: "Cellular origins of Barrett’s esophagus and its role in development of adenocarcinoma"
Institution: Dana-Farber Cancer Institute
Named Award: William Raveis Charitable Fund Physician-Scientist
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Ramesh A. Shivdasani, MD, PhD
Cancer Type: Gastric, Other Cancer
Research Area: Epigenetics
Peter J. Turnbaugh, PhD

[Nadia’s Gift Foundation Innovator]

Variations in drug efficacy and toxicity between patients are a major limitation to the long-term treatment of cancer. Even if the initial treatment is successful, cancers can return due to the emergence of cancer drug resistance. Dr. Turnbaugh seeks to determine how the gut microbiome (bacteria residing in the human body) contributes to drug efficacy and resistance. He will combine microbiology and pharmacology approaches to identify new microbiome-based biomarkers for monitoring and predicting acquired drug resistance. The findings will also have broad implications for development of more effective treatment regimens for patients with colorectal as well as other cancers

Project title: "The gut microbiome: an unexpected contributor to cancer drug resistance"
Institution: University of California, San Francisco
Named Award: Nadia’s Gift Foundation Innovator
Award Program: Innovator
Cancer Type: Colorectal
Research Area: Microbiology
Eric Wang, PhD

Dr. Wang is applying a chemical biology approach to identify kinases and small molecule inhibitors that enhance the immune system’s tumor surveillance capabilities. Therapies that enhance the anti-tumor activity of the immune system have shown tremendous promise in patients; however, only a subset of patients and tumors respond well to such treatments, so identifying complementary strategies to increase the effectiveness of existing immunotherapies is increasingly important. His goal is to obtain mechanistic insight into the anti-tumor immune response and to identify small molecule drugs that may improve the efficacy of immunotherapies in patients.

Project title: "Enhancing anti-tumor immunity via pharmacological inhibition of kinases"
Institution: Dana-Farber Cancer Institute
Named Award: Robert Black Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Nathanael Gray, PhD
Cancer Type: Colorectal
Research Area: Chemical Biology
Peter M. K. Westcott, PhD

Dr. Westcott is developing improved in vivo models for studying the complex interactions between colorectal cancer and the immune system. The powerful genome editing technology CRISPR-Cas9 will be leveraged to rapidly generate a suite of novel mouse models of colorectal cancer harboring distinct mutational signatures seen in human cancer. He will use genome-wide sequencing and preclinical studies to dissect the role of these mutational signatures in promoting cancer cell detection by the immune system, and in modulating response to immunotherapies. These studies will provide new tools to probe fundamental questions of tumor immunology, with the ultimate goal of improving the poor response of colorectal cancers to immunotherapies.

Project title: "Exploiting endogenous mutational processes in cancer to enhance response to immunotherapy"
Institution: Massachusetts Institute of Technology
Award Program: Fellow
Sponsor(s) / Mentor(s): Tyler Jacks, PhD
Cancer Type: Colorectal
Research Area: Animal Models/Mouse Models
Heather L. Yeo, MD

The cost of gastrointestinal cancer care in older adults is high, and hospital readmission after major GI cancer surgery can be particularly costly. The Center for Medicare Services (CMS) estimates that around 75% of these readmissions are preventable. For these patients, early warning signs for dehydration, infection, or other complications, if noted earlier, would allow physicians to intervene and prevent readmission. Dr. Yeo, a surgeon, has worked with programmers from Cornell Tech Campus to develop a Mobile Application (iPhone or Android compatible) for patients undergoing abdominal cancer surgery. The app tracks patients’ mobility and prompts patients to input quantitative and qualitative data regarding pain, fluid status and dietary factors in order to allow physicians to intervene earlier as needed. She is currently piloting the app for feasibility and usability, and improving the user interface so that physicians can use the app to monitor and improve patient care. The next step is a prospective randomized study to evaluate the utility of this mobile app in the prevention of readmission, thus enhancing physician-patient interactions, decreasing costs and, most importantly, improving patient care.

Project title: "Use of mobile applications to evaluate post surgical recovery in aging patients with GI cancer"
Institution: Weill Cornell Medicine
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Manish A. Shah, MD, and Deborah L. Estrin, PhD
Cancer Type: Gastric, Other Cancer, Colorectal, Pancreatic
Research Area: Outcomes Research
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