Dr. Collins is the University of Michigan Department of Internal Medicine Collegiate Professor of HIV Research, Professor of Microbiology and Immunology and Senior Scholar of The A. Alfred Taubman Medical Research Institute. Dr. Collins’ research has focused on understanding HIV persistence as an independent investigator for over 20 years. Following initial training in immunology and virology her laboratory made important contributions to understanding the role of HIV accessory proteins in immune evasion. Dr. Collins showed that the HIV Nef protein reduces cell surface expression of MHC-I and protects infected primary T cells from CTL recognition. Her laboratory is currently developing a highly potent inhibitor of Nef that reverses MHC-I downmodulation. Nef inhibitors are exciting potential drugs because they provide a mechanism to enhance CTL recognition and clearance of infected cells that persist in people with suppressed HIV infection on cART. People in the Collins laboratory determined the molecular mechanism by which Nef disrupts MHC-I trafficking and limits CTL recognition. They demonstrated that Nef stabilizes an interaction between the clathrin adaptor protein-1 (AP-1), ARF-1 and MHC-I to direct MHC-I into the endolysosomal pathway instead of to the cell surface. They also showed that β-COP is a second trafficking protein utilized by Nef to facilitate MHC-I degradation. These studies have been very influential. The AP-1 μ1-Nef-MHC-I complex the Collins Lab identified and characterized using biochemical approaches is a key target of current approaches to develop a Nef inhibitor. The Collins lab has also discovered an important role for the HIV Vpr accessory protein. They determined that Vpr counteracts restriction factors in T cells and in macrophages. Her lab is currently determining the identity of the macrophage restriction factor. These contributions expanded to include HIV latency following a discovery that HIV preferentially achieves a latent infection in primitive hematopoietic stem/progenitor cells (HSPCs) more than a decade ago. Since then, her lab has generated evidence supporting an important role for infected HSPCs in vivo by isolating provirus from highly purified populations of HSPCs. Her lab also characterized the co-receptors that support HIV infection of HSPCs; CXCR4 is present on nearly all CD4-positive HSPCs whereas CCR5 is present on a more differentiated subset that is capable of long-term persistence. Consistent with this, her lab identified proviral genomes of both tropisms in preparations of HSPCs from HIV infected people. Recently, her laboratory reported that clonally amplified intact proviral genomes from HSPCs and their progeny match residual plasma virus and do so more frequently than proviral DNA that was not amplified. Dr. Collins is an elected member of ASCI (2005), the Association of American Physicians (2012), and the National Academy of Medicine (2016).
Kathleen L. Collins, MD, PhD