Research in the Wang Laboratory consists of projects in three main directions: 1) To elucidate the molecular mechanisms for the regulation of mitochondrial autophagy; 2) To study the molecular mechanisms for immunological memory against infections; and 3) To develop a cure for HIV infection by the SECH approach through selective elimination of host cells harboring replication-competent HIV:

1. Autophagy is critical for mitochondrial quality control through the clearance of dysfunctional mitochondria. Autophagy is also important for the maintenance of mitochondrial homeostasis and the regulation of cellular metabolic functions. We have identified novel signaling complexes that regulate the specificity for mitochondrial autophagy by mass spectrometry. Ongoing studies aim to understand the molecular mechanisms for the specific recognition of dysfunctional or surplus mitochondria for degradation by autophagy. How selective mitochondrial autophagy regulates diverse cellular functions and protects the cellular fitness and longevity are being studied.

2. 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. We have discovered an essential role for autophagy in the long-term maintenance of memory B cells against influenza. We aim to characterize the molecular mechanisms for immunological memory to facilitate the development of more effective vaccines against epidemic and pandemic infections.

3. 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. We have described a strategy to eradicate HIV infection by selective elimination of host cells harboring replication competent HIV (SECH). 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 patients. We will further investigate the efficacy and safety of SECH for HIV eradication in preclinical studies, and develop SECH as a therapeutic approach for treating people living with HIV.