Research

Our lab is interested in studying the role of menin in colonic epithelial homeostasis and colorectal cancer tumorigenesis.  Menin, which is encoded by the MEN1 gene, is a nuclear epigenetic regulator with both tumor promoting and tumor suppressing functions.  We demonstrated that menin is over-expressed in CRC, and plays a key role in promoting transcription of pro-tumorigenic SKP2.  Furthermore, we also demonstrated that menin serves as a repressor of glycolysis in CRC cells, through an mTOR independent mechanism.  Additionally, we showed that combined treatment with a menin inhibitor, to reduce SKP2 transcription and increase glycolysis, and a small molecule EGFR inhibitor synergistically killed CRC cells in cell culture and in mouse xenografts.  Further ongoing studies are focused on the role of menin in regulating colonic epithelial metabolism and how this metabolic regulation may influence colonic tumorigenesis.

We also have an active ongoing CRC organoid research program, in collaboration with Dr. Chris Lengner and Dr. Ning Li.  This programs utilizes freshly collected CRC specimens to perform single cell sequencing and establish patient-derived organoids and tumoroids to allow for the detailed study of tumor microenvironment interactions.

We are involved in all aspects of Lynch syndrome research, from basic biology, to clinical surveillance strategies, to increasing access to genetic testing.  We have ongoing biosample acquisition studies, including LIP² (Lynch syndrome Immune Profiling Project) and LIMBO (Lynch syndrome mucosal Immune and MicroBiOme initiative) which are being conducted in collaboration with Dr. E. John Wherry, and are focused on trying to characterize and understand the implications of the peripheral and mucosal immune systems in Lynch syndrome.  We are also interested in surveillance strategies for cancer prevention in Lynch syndrome, with recent data from our group supporting the use of upper GI surveillance as a regular part of a comprehensive Lynch syndrome surveillance plan.  Finally, we shown that significant disparities exist in delivery of GI cancer genetic care, and therefore we are also interested in facilitating improvements in delivery and uptake of GI cancer genetic care in order to eliminate disparities, and to ensure that all individuals have access to these extremely important services.

Our lab is interested in colonic polyposis, and now polyp growth may be regulated by genetic factors, microbiome/metabolome factors, or a combination of the two.  We have ongoing active study protocols where we collect and analyze microbiome samples from individuals with and without colonic polyposis, which is performed in collaboration with Dr. Josephine Ni.

Understanding the role of germline genetic predisposition for gastric cancer is another major focus of our lab.  We are primarily interested in hereditary diffuse gastric cancer, which can be caused by a disease-causing variant in either CDH1 or CTNNA1.  Our group published the first large-scale analysis of CTNNA1 sequencing results from multigene panel testing, and we have the ongoing CTNNA1 Familial Expansion (CAFÉ) Study to better determine cancer risks of CTNNA1 loss-of-function carriers.  We also an active collaboration with Dr. Sandra Ryeom where we are using patient-derived gastric organoid models to better understand the role that germline risk variants play in gastric tumorigenesis.

Early detection of pancreatic cancer in individuals at increased pancreatic cancer risk is a major focus of our research program.  We have multiple ongoing early detection studies including the multi-center, NCI-funded Cancer of the Pancreas Screening-5 (CAPS5) Study, the international Pancreatic Cancer Early Detection (PRECEDE) Consortium Study, and our own center's study entitled Preliminary Evaluation of Screening for Pancreatic Cancer in Patients with Inherited Genetic Risk.  Through these multiple studies we are accruing data and biosamples to aid in optimizing pancreatic cancer early detection.  We also have ongoing collaborations with Dr. Ken Zaret and Dr. Erica Carpenter to develop novel assays for pancreatic cancer early detection.