Research Philosophy: Projects in the lab generally start by thinking deeply about the clinical circumstances that encase the diagnosis, management, and treatment of gastrointestinal cancers. With this holistic view in mind, we aim to identify unmet needs and clear gaps in translation, which directly inform the design of molecular studies involving patient samples (Cancer Genomics). The molecular studies describe key features of human disease and help generate new, testable hypotheses. Patient-derived data help guide the development of innovative models that are designed to recapitulate human disease and utilized to rigorously test emergent hypotheses (Disease Models). The combination of patient-derived molecular data and faithful models help elucidate crucial disease mechanisms that promote cancer progression. The insight gained directly informs new screening platforms to uncover molecular dependencies and hopefully lead to drug discovery (Therapeutic Vulnerabilities). Our lab applies this investigative philosophy to two main areas of gastrointestinal cancer research.
Gastric and esophageal cancers: One avenue of investigation is devoted to better understanding cancers of the stomach and lower esophagus. We design model systems that integrate disease risk factors with early genetic mistakes to study the premalignant state,hoping to learn how somatic mutations engage environmental exposures during the initiation of these cancers. These models have yielded new insight into disease progression, revealing therapeutic vulnerabilities that are actively being investigated in preclinical systems. By leveraging data from patients, mouse models, and cell culture studies, we are motivated to provide an integrated understanding of early events in gastrointestinal cancers with the ultimate hope that the knowledge gained will inspire new avenues for cancer prevention and treatment.
Colorectal cancer: The second research domain that our lab is invested in centers around colorectal cancer, which remains the second leading cause of cancer-mortality worldwide and responsible for an alarming trend in young patients. The intestine is a special organ in that it is the most rapidly renewing tissue in our body; the gut lining is replenished every 2 to 5 days, which is simply remarkable. Maintaining the intestinal lining therefore requires stem cells to constantly give rise to mature cells to perform their specialized function before dying. Disruption of this natural maturation is a hallmark of colorectal cancer.Our lab is focused on defining the molecular components that block proper differentiation of cancer cells. We have also designed a unique discovery platform to help us screen thousands of drugs to find the specific agents that overcome this block in maturation. We strongly believe the next generation of therapeutics will restore proper maturation in colon cancer cells, reprogramming them to live out their natural life cycle. We have also noticed that factors responsible for stem cell behavior are mutated in a subset of colorectal cancer. Using innovative mouse models and cutting-edge technology, we hope to define the clinical and functional significance of these recurrent mutations.