Justin Mott

Associate  Professor, Biochemistry and Molecular Biology

Justin Mott Phone: 402-559-3177 (Office)
    Location: BCC 6.12.395
402-559-3170 (Lab)
    Location: BCC 6.12.408
Fax: 402-559-6650

M.D., Saint Louis University, St. Louis, Missouri 2004
Ph.D., Saint Louis University, St. Louis, Missouri 2003


Research Opportunities in my laboratory:
Graduate students considered on an individual basis
Medical students, summer research

Research Interests:
Cholangiocarcinoma (liver cancer)
Cholangiocyte injury in non-alcoholic steatohepatitis
MicroRNA expression and function
Apoptosis resistance mechanisms

Dr. Mott's Research Interests

Dr. Mott's Lab Members
Lab members:
Mary Anne Phillippi, Cody Wehrkamp, Justin Mott, Ashley Mohr, and Bailey Stringham

Staff Staff
Staff Staff Staff

Research Projects

Bailey Stringham, Technologist

Bailey is studying lipid signaling in cholangiocytes and other cells important in metabolic syndrome. She has demonstrated regulation of miR-34a by fatty acids in pathophysiologic conditions of NASH.


Mary Anne Phillippi, Lab Manager

Mary Anne is the lead surgeon for tumor experiments and has projects in both cancer and NASH model systems. Her efforts have recently uncovered unexpected signaling from free fatty acids in cholangiocytes.

Cody Wehrkamp, Ph.D. Candidate

Cody is investigating cancer signaling in response to miR-106b, a microRNA that is increased in cholangiocarcinoma. He has investigated miR-106b targets and the functional effects on cell death and tumor progression.

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 the prognosis is poor.  In part, this is due to resistance of tumor cells to apoptosis upon chemotherapy or targeted therapy. 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.

MicroRNA Signaling
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.

Additional pathways whereby microRNAs regulate apoptosis are being pursued. This includes regulation of microRNA expression by disease signaling and identification of novel targets of microRNAs. We have data implicating the oncogenic mir-106b~25 cluster in regulating TRAIL death receptor signaling. Promising data to date illustrate that miR-25 is antiapoptotic by way of targeting DR4 and antagonism of miR-25 promotes cholangiocarcinoma cell death.


Link to Mott Lab publications on PubMed
Link to full text manuscripts (if available) from the UNMC digital commons website
Link to Dr. Mott’s profile at the Nebraska Gateway to Nutrigenomics