Dr. Badley's Human Immunodeficiency Virus Laboratory is focused on understanding how cell death regulation impacts the outcome of human diseases, including HIV. The lab is currently pursuing two major projects.
Our researchers propose to cure HIV infection with a prime shock and kill approach. HIV-1 infected T cells are intrinsically resistant to apoptosis, because HIV proteins alter expression of a wide variety of apoptosis regulatory proteins. Also, resting memory T cells, which are a major component of the HIV reservoir, are destined to persist, as they consitute a historical archive of prior immune responses. Thus, when HIV reactivates from latency, these cells (and others) are not killed by the proapoptotic effects of HIV replication or by immune clearance. Our approach is to prime these cells toward an apoptosis-susceptible phenotype and then induce HIV reactivation.
- Drugs currently in preclinical or clinical testing for this purpose include venetoclax and ixazomib
Another major focus in our lab is a novel TRAIL splice variant called TRAILshort, which our lab discovered. This variant blocks TRAIL-mediated killing. We are studying the regulation of TRAILshort, the signaling induced by TRAILshort, and the biologic relevance of TRAILshort in HIV and other disease states, including cancer.
- Our translational studies on TRAILshort are focused on developing methods to inhibit TRAILshort in order to restore TRAIL-mediated clearance of unwanted virally infected or cancerous cells.