The Whitehurst lab is seeking energetic, dedicated graduate students and post-doctoral fellows to join our groups. Please see below for current projects.
Study of Cancer-Testis Antigens (also known as Cancer Germline Genes) that alter mitochondrial dynamics. Cancer-Testis Antigens are normally only expressed in testis. We have discovered a cohort of Cancer-Testis Antigens are expressed in tumor cells and localize to the mitochondria. Inhibition of these proteins leads to a loss of tumor cell viability. This project will focus on understanding how these proteins promote tumor cell survival by altering mitochondrial behavior including fission-fusion dynamics, oxidative phosphorylation, mitophagy and/or apoptosis. These studies will involve microscopy, live-cell imaging, Seahorse analysis, etc. This study will reveal novel mechanisms by which tumor cells modulate mitochondrial function. Ultimately, these proteins could represent therapeutic targets for anti-cancer therapy.
Study of Cancer-Testis Antigens that regulate DNA damage and repair. Our work has identified a number of Cancer-Testis antigens that promote DNA damage and repair. This project will involve delineating the molecular mechanisms by which these Cancer-Testis Antigens promote repair. The starting point uses a protein interaction network that was previously generated and identified potential candidate interacting partners (RAD51, H2AX, etc.). This study will focus on the functional interaction of Cancer-Testis Antigens with these candidate interacting partners in the context of DNA damage assays, radiosensitivity, and chemosensitivity. Study of these proteins will reveal previously unrecognized mechanisms by which tumors cells cope with DNA damage. One hypothesis is that tumors expressing DNA damage CTAs may exhibit altered sensitivity to DNA-damaging agents.
Synthetic Lethality of CDK4/6 Inhibitors. CDK4/6 inhibitors are highly effective in treating ER-positive breast cancer, but have not exhibited significant efficacy in lung cancer. We have identified a subset of lung cancer tumors that exhibit exquisite sensitivity to CDK4/6 inhibition. We have generated molecular signatures from these tumors and nominated protein candidates required for modulating sensitivity or resistance to these agents. This study will involve synthetic lethal loss of function (siRNA, CRISPR) screening and gain of function screens to test the requirement for these proteins in CDK4/6 inhibition. The objective of this study will be to identify synthetic lethal partners of CDK4/6 inhibitors that may be pharmacologically accessible to enhance responsiveness to these inhibitors in lung cancer patients.
To learn more, please send a CV to firstname.lastname@example.org.