Therapies that directly target cancer-promoting oncoproteins have revolutionized the treatment of cancer. Cancers, however, are primed to adapt and evolve in the presence of treatment, resulting in an ability to resume growth despite the presence of therapy. Utilizing cutting-edge new techniques that allow the determination of genetic alterations in single cancer cells, Piro aims to understand the principles that govern the evolution of resistance during therapy and identify novel therapeutic interventions that halt this process. His specific focus will be on improving the efficacy of KRAS inhibition for treatment of lung and colorectal cancers.

Dr. Overacre-Delgoffe is utilizing unique tools to address how the interaction between the host’s immune system and gut microbes affects colon tumor progression and patient responsiveness to current immunotherapies. Currently, colon cancer patients show an extremely limited response to immune-based therapies and have very poor survival rates. The colon is a unique environment that is composed of host cells and numerous bacteria and microbes that have evolved with the host. Dr. Overacre-Delgoffe aims to understand the basic mechanisms of immunotherapy resistance due to microbiome-immune system interactions, which may aid in developing more effective therapeutics for colon cancer.

Dr. Puchades studies ion channels – proteins embedded in the membrane surrounding a cell.  They act as molecular gates, opening in response to diverse stimuli to allow ions to flow into cells. The essential ion channel TMEM16A is required for many fundamental physiological processes, including neuronal signaling, muscle contraction, and salivary gland secretion. In cancer cells, increased activity of TMEM16A is closely linked to metastatic progression in esophageal, gastric, and pancreatic cancers. Dr. Puchades aims to understand how TMEM16A functions and how drug molecules hinder its activity. This research has the potential to guide the pharmacological targeting of TMEM16A as a novel approach for the development of anti-cancer therapeutics.

Dr. Ramanan studies the interplay between commensal microbes and immune cells in the intestine, and how these interactions influence the progression of inflammation and colorectal cancer. Her research particularly focuses on a cell type that dampens inflammatory responses, known as regulatory T cells. In the intestine, these cells can be broadly categorized into two subsets that differ in origin and responsiveness to microbes, but their exact functions remain unclear. She aims to identify the specific functions of these different subsets in intestinal inflammation, tissue repair, and tumor pathogenesis. These studies could provide invaluable information that can be harnessed to improve current cancer immunotherapy options.  

Dr. Sefik is examining the connection between obesity, cancer and the microbiome. An estimated 600 million people worldwide suffer from obesity, with 15-20% of deaths from cancer in the US alone linked to obesity. Recent studies in mice highlight the importance of intestinal bacteria and immune cells in obesity and colorectal cancer; however, these roles are not yet well characterized in humans. She will   analyze how high fat diet and obesity-associated intestinal bacteria change intestinal immunity in mice that harbor the human immune system and the human microbiota. This will help resolve some of the existing discrepancies and discover new players that are relevant to obesity and cancer in humans and help engineer better-targeted, combined therapies to colorectal cancer, especially in cases where existing immunotherapy fails.

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.