Colorectal cancer (CRC) is the second deadliest cancer in the United States. While localized CRC can be treated surgically and has a 5-year survival rate of 91%, the survival rate of metastatic CRC falls dramatically to 15%.  Chemotherapy in advanced cases is largely palliative, as nearly all patients develop resistance to current treatments.  Therefore, understanding the mechanisms of drug resistance and metastasis is essential to developing effective therapies for disseminated CRC.  Claudins are being investigated as therapeutic targets because of their tissue-specific expression, selective upregulation in cancer, and presence on the cell surface.  Claudin-1 (CLDN1) is highly upregulated in CRC, and its overexpression promotes oncogenic signaling and an aggressive, metastatic phenotype; however, since claudins are not enzymatically active, it is unclear how they influence intracellular signaling. Our research shows that, in colon cancer, CLDN1 interacts with the receptor tyrosine kinase EPHA2 to promote a stem-like, chemoresistant phenotype. Ongoing research is investigating how CLDN1 promotes metastasis. Additionally, Mark will discuss his non-traditional career path, his relationship with bioinformatics as a bench scientist, and how the Cancer Genomics Cloud has helped in his research and training. 

Graphical Abstract

The investigated role of claudins in colorectal cancer and chemoresistance.

 About the Speaker

Mark Primeaux is a PhD student in Biochemistry & Molecular Biology at the University of Nebraska Medical Center under the mentorship of Dr. Punita Dhawan.  He earned his BS in Biology at the University of Massachusetts Amherst.  His research interests are the biochemical and microenvironmental factors underlying therapy resistance and metastasis in cancer. He recently received the prestigious F99/K00 Predoctoral to Postdoctoral Fellow Transition Award from the National Cancer Institute and has accepted a postdoctoral position with Dr. Cyrus Ghajar at the Fred Hutchinson Cancer Institute.