Andy Q. Yu, MD, PhD
Associate Professor of Microbiology & Immunology
Titles & Appointments
- Associate Professor of Medicine
Dr. Yu's laboratory mainly focuses on the immunopathology of HIV infection, and the clinical and immunological interactions between HIV and other human persistent viruses like HCV.
The reasons for the failure of the immune system to control HIV infection, and the resulting immunodeficiency, remain unclear. Infection with HIV is characterized by both continual virus replication and a vigorous immune response. Antibodies are elicited early in infection and are generally vigorous at all stages of HIV infection. However, these antibodies are unable to clear virus particles and infected cells by actions of the complement system, phagocytes or killer cells. Similarly, HIV infection is associated with an extremely vigorous virus-specific cytotoxic T-lymphocyte (CTL) response, but HIV disease ultimately progresses. Dr. Yu's laboratory is interested in understanding the molecular mechanisms by which HIV/HIV-infected cells provide resistance to antibody-dependent complement-mediated virotoxicity/cytotoxicity, and by which the continuous presence of the viral antigen(s) renders virus-specific T cells to become dysfunctional. The major areas of Dr. Yu's current research are: (1) Eradication of HIV reservoirs. We have investigated the abrogation of complement control protein function to facilitate HIV-specific antibodies in patient plasma to lyze the complement-resistant HIV virions. We are using this strategy to kill HIV-infected cells through complement-mediated cell lysis in order to eradicate HIV reservoirs. (2) Novel strategies to aid in vaccine design to enhance cellular immunity to persistent virus infection in immunocompromised hosts and aged individuals. We have incorporated the TNF superfamily molecules including CD40L, RANKL, and Ox40L, pivotal costimulatory molecules for immune responses, into poxvirus vectors in order to test their adjuvant activity in enhancing immunogenicity of poxvirus-based HIV vaccines. Co-immunization of regular mice with CD40L-expressing poxvirus and poxvirus-based HIV vaccines augmented HIV-1 specific CTL responses in terms of frequency, polyfunctionality and IL-7 receptor alpha chain expression. We are particularly interesting in exploring the adjuvant activity of these constructs in enhancing immunogenicity of HIV vaccines in CD4+ T cell-deficient or aged murine models. (3) Clinical and immunological interaction between HIV and HCV. We are interesting to investigate why HIV coinfection is associated with enhanced HCV replication, increased hepatic inflammation and fibrosis, and more rapid progression to cirrhosis and end-stage liver disease.