Associate Professor, Biochemistry and Molecular Biology
M.D., Saint Louis University, St. Louis, Missouri 2004
Ph.D., Saint Louis University, St. Louis, Missouri 2003
Postdoctoral fellowship, Mayo Clinic, Rochester Minnesota 2011
Dr. Mott heads a research program to use innovative models and techniques for the study of liver cancer. Specifically, research in the Mott lab is focused on cholangiocarcinoma, a biliary tract cancer. He is engaged in medical education, STEM outreach, and mentoring.
We have learned that science is a team effort and we work to make a laboratory environment that encourages success in and beyond science. This means treating trainees with respect, encouraging outside activities, fostering a creative environment, and building a collaborative team. We have also learned from patients who have been diagnosed with cholangiocarcinoma. Their resilience and willingness to share their experiences and hopes with us motivate our studies.
Research Opportunities in my laboratory:
The Mott Laboratory has a healthy environment to pursue science and thrive as a person. We value inclusion and benefit from new perspectives. On an individual basis, research opportunities are available for students who want to learn and study liver cancer.
Cholangiocarcinoma (liver cancer)
Cholangiocyte injury in non-alcoholic steatohepatitis
MicroRNA expression and function
Apoptosis resistance mechanisms
Lab members: (from L) Morgan Shipley, Andrew Phillips, Cody Wehrkamp, Justin Mott, Ashley Mohr, Matt Spriet, Mary Anne Phillippi
Dr. Ashley Mohr is an expert in cancer cell signaling and mentors students in imaging, FGFR biology, and cholangiocarcinoma progression. She has studied pancreatic and liver cancers, circulating tumor cells, microRNA, and in vivo tumor models.
Matt Spriet is a PhD candidate studying regulation and function of microRNAs in cholangiocarcinoma.
Andrew Phillips is a PhD candidate exploring posttranslational modifications of FGFR4 in expression and function in cholangiocarcinoma.
Yamnah Hafeji is a Master’s student studying intracellular signaling pathways in liver cancer.
Cholangiocarcinoma cell death mechanisms
My lab is focused on cell death in liver cancer, specifically cholangiocarcinoma, a malignant tumor arising in the bile duct epithelium. Clinically, this tumor is very difficult to treat and new treatment options are needed. Resistance of tumor cells to apoptosis upon chemotherapy or targeted therapy is a challenge. Cholangiocarcinoma cells resist apoptotic signaling induced by TRAIL (a tumor surveillance death ligand), both through increased expression of anti-apoptotic microRNAs and through decreased expression of pro-apoptotic microRNAs. Further studies are investigating FGFR4 signaling in malignant disease progression. Decreased apoptosis signaling may impact the response to anti-tumor therapies, and reversing this resistance has the potential to improve treatment of this devastating disease.
Non-alcoholic fatty liver disease
Injury in non-alcoholic fatty liver disease is mediated in part by elevated circulating free fatty acids. Previous work has demonstrated that hepatocytes are sensitive to lipoapoptosis when treated with free fatty acids, contributing to liver disease. We have shown that free fatty acids cause cholangiocyte lipoapoptosis, suggesting that injury to ductular epithelium may contribute to pathology. Other labs have shown that cholangiocyte proliferation correlates with fibrosis and NASH severity. Further, bile duct swelling and loss are also observed in a subset of patients who have a cholestatic NASH presentation. We propose that cholangiocyte injury causes progression and worsening of NASH.
I have established a distinct line of investigation into dysregulation of microRNAs in cholangiocarcinoma and the effects on cell death signaling in malignant and non-malignant liver processes. MicroRNA levels are commonly altered in disease and these changes have the potential to affect hundreds of gene targets and significantly influence cell function. For instance, we discovered that Mcl-1 protein levels are decreased by microRNA-mediated silencing, and specifically that miR-29b targets Mcl-1 in cholangiocytes. This regulation is lost in malignant cells which have lower levels of miR-29b. Increasing the cellular miR-29b levels rendered malignant cells sensitive to TRAIL killing.