Professor of Transplant Immunology in Surgery, Academic Institute
Full Member, Research Institute
Weill Cornell Medical College
The goal of our laboratory is to develop novel strategies to combat pathogens that cause epidemic and pandemic infections. Research projects in the laboratory are focused on two areas: 1) To study the molecular mechanisms for immunological memory against infections; and 2) To develop a cure for HIV infection by the SECH approach through selective elimination of host cells harboring replication-competent HIV.
The generation of immunological memory by forming immune memory cells against pathogens is essential for the success of vaccines. We are studying the molecular mechanisms governing the formation and maintenance of immune memory cells. To this end, we have discovered an essential role for autophagy in the long-term maintenance of memory B cells against influenza. Our study suggests that autophagy is required for the success of vaccines by protecting the long-term survival of immune memory cells. Our work will facilitate the development of more effective vaccines to protect against epidemic and pandemic infections.
We have developed an approach to eradicate HIV infection by selective elimination of host cells harboring replication-competent HIV (SECH). The RNA genome of HIV is reverse-transcribed into DNA and integrated into the genome of host cells, resulting in persistent infections that are difficult to clear. The SECH approach combines viral reactivation with induction of cell death and inhibition of autophagy to specifically delete host cells capable of producing HIV. SECH can clear HIV-1 infection in humanized mice, and in PBMCs from HIV-1 patients. Our work demonstrates SECH as a cure strategy to eradicate HIV infection that is applicable to the general population. We will continue to study the mechanisms for SECH in the clearance of HIV-infected cells. We will determine the efficacy of SECH for HIV eradication in pre-clinical studies, and develop SECH as a therapeutic approach for treating people living with HIV.