Mentor: Giovanna Tosato, M.D. | tosatog@mail.nih.gov
Mentor: Michael DiPrima, Ph.D. | diprimamj@mail.nih.gov
Lab: Cellular and Molecular Biology Section

Targeting Eph Tyrosine Kinase Receptors in Colorectal Cancer

The laboratory is focused on the study of cancer, including discovery of cancer cell vulnerabilities that can be targeted with new therapeutic approaches. One project is focused on colorectal cancer, a leading cause of cancer death worldwide. Recently, we have discovered that Eph tyrosine kinase receptors control the growth and survival of colorectal cancer cells and have exploited this discovery to develop small molecule tyrosine kinase inhibitors (TKI) that effectively reduce the growth or induce cell death in colorectal cancer cells. In the context of this project, we are evaluating promising TKI through in vitro studies and pre-clinical experimentation in mice. An important component of the study is the dissection of Eph receptor signaling in normal epithelial cells and colorectal cancer cells, and discovery of how the TKI alter Eph receptor signaling. Other important components are development of organoid culture systems of primary colorectal cancer cells and evaluation of functional outcomes of exposing colorectal cancer cells to the TKI, including growth arrest, development of cell senescence or cell death by activation of distinct death pathways.  We use a variety of experimental approaches to advance research, including genetic, epigenetic, and biochemical approaches to study genes, gene expression, mRNA translation, and proteins; we use a variety of cell-based systems and mouse models of cancer. The student will be paired with a post-doctoral fellow in the laboratory and will work under supervision to the extent necessary with the goal of making the experience valuable for the student.

 

Intern Name: Kevin Gery
Institution: University of Rochester
Project Title: Novel Eph receptor TKIs induce cellular senescence in colon cancer cell lines