The primary focus of our laboratory is to understand the host-pathogen interactions and to use this knowledge to develop therapeutics and preventive vaccines for viral infections such as HIV. We are currently focusing on;
(1) Understanding the role of innate immune cells (NK/ILC/monocytes) in HIV/SIV pathogenesis and preventive vaccines
(2) Investigating the role of innate immunity in HIV/TB co-infection and BCG vaccination.
(3) Studying the Immunopathogenesis of SARS-CoV-2, COVID-19-associated cardiometabolic complications, and the development of therapeutics.
(1) Understand the innate immune cells (NK/ ILC/ monocytes) in HIV/SIV pathogenesis and prevention:
Innate immune cells such as NK, Innate lymphoid cells (ILCs), and monocytes are first responders to viral infections. They not only restrict invading pathogens in the initial phase of the infection but also modulate adaptive immune responses, which are essential to prevent or control infections. The exact role innate immune cells play in regulating HIV infection and treatment remains unclear. Employing a macaque-SIV infection model, we have found a crucial role for mucosal and systemic NK/ ILCs and monocytes in viral pathogenesis and the efficacy of antiviral therapy (ART). We also uncovered a critical role for mucosal NK/ILCs in HIV preventive vaccine-induced protection from infection in the rhesus macaque model. We are currently studying the innate memory generated by HIV preventive vaccines and expect to target these immune cells with adjuvants to enhance vaccine efficacy. In collaboration with Dirajlal-Fargo Lab at Case Western Reserve and Funderburg lab at OSU, we are studying the role of trained immunity (NK, ILC, and Monocyte) in the pathogenesis of cardiovascular disease (CVD) in HIV-infected ART-treated children in a longitudinal study in the US and Uganda. The results of this study will help us introduce new treatment modalities to reduce CVD in HIV-infected individuals.
(2) Investigate the role of innate immunity in HIV/TB co-infection and BCG vaccination:
Mycobacterium infections (MTB and Non-MTB) are the leading cause of death among people living with HIV. BCG is the only licensed vaccine against tuberculosis, and the modest protection provided by BCG vaccination is age-dependent and highly variable. However, the effect of Mycobacterial infections and BCG vaccination in immunocompromised individuals is poorly understood. A worrisome recent finding is that BCG vaccination may increase the risk of vertical HIV transmission. To begin piecing together these puzzles, we are currently investigating immune responses to mycobacterial infections and BCG vaccination in human (HIV+ and HIV-) and mouse models.
(3) Studying Immunopathogenesis of SARS-CoV-2, COVID-19-associated cardiometabolic complications, and development of therapeutics.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐ 2) infection, which causes Coronavirus Disease 2019 (COVID-19), has led to a global public health emergency. An effective and appropriate immune response is essential to control and eliminate viral infections. However, an excessive immune response may lead to immunopathology in COVID-19 patients. Understanding the interplay between innate (monocytes, neutrophils, NK cells) and adaptive immune cells (B-cells and T-cells) and the pro-inflammatory and pro-coagulant mediators they produce is crucial for developing various treatments and prevention strategies. In collaboration with OSU clinicians in the Division of Pulmonary and Critical Care Medicine, we have been comparing immune pathology in severe, moderate, and mild COVID-19 patients and found excessive activation of innate immune responses in severe COVID-19 patients. Furthermore, we identified increased cardiometabolic biomarkers in severe COVID-19 patients compared to patients with mild and moderate symptoms. We are currently studying the risk of future CVD in adult and pediatric patients who had previously suffered from severe COVID-19. We also investigate immunogens/ adjuvants to enhance anti-COVID immunity and therapeutics in mice and humans.