We study human B cells and neutralizing antibody responses against hepatitis C virus (HCV), hepatitis B virus (HBV), SARS-CoV-2, and respiratory syncytial virus (RSV). Our overarching hypothesis is that understanding the B cell response in individuals who naturally control infections, and those who have been vaccinated, can help us to understand the basic biology behind successful immune responses, leading to design of more effective vaccines. A particular technical strength of our laboratory is high dimensional flow cytometric analysis of antigen-specific B cells, which allows us to phenotype these rare cells, and also to sequence B cell receptor (BCR) repertoires and isolate virus-neutralizing monoclonal antibodies (mAbs).

The David Thomas Lab oversees clinical research projects that aim to understand the natural history and pathogenesis of hepatitis C virus infection. A special area of clinical and research focus is liver disease in HIV-infected people.

Research in the Andrea Cox Lab explores the immune response in chronic viral infections, with a focus on HIV and the hepatitis C virus (HCV). In our studies, we examine the role of the immune response upon exposure to HCV by examining responses to HCV in a longitudinal, prospective group of high-risk individuals. This enables us to compare the innate, humoral and cellular immune responses to infection with clearance versus persistence. Through our findings, we seek to identify mechanisms of protective immunity against HCV infection and improve HCV vaccine design.

Dr. Christine Durand, assistant professor of medicine and oncology and member of the Johns Hopkins Kimmel Cancer Center, is involved in clinical and translational research focused on individuals infected with HIV and hepatitis C virus who require cancer and transplant therapies. Her current research efforts include looking at outcomes of hepatitis C treatment after solid organ transplant, the potential use of organs from HIV-infected donors for HIV-infected solid organ transplant candidates, and HIV cure strategies including bone marrow transplantation. Dr. Durand is supported by multiple grants: • R01 from the National Institute of Allergy and Infectious Diseases (NIAID) to study HIV-to-HIV organ transplantation in the US. • K23 from the National Cancer Institute (NCI) to study antiretroviral therapy during bone marrow transplant in HIV-1 infection. • U01 from the NIAID to study HIV-to-HIV deceased donor kidney transplantation. U01 from the NIAID to study HIV-to-HIV deceased donor liver transplantation.

The Balagopal Lab has adapted high-resolution tools to study viruses in situ. Specifically, we were the first to quantify hepatitis C virus (HCV) infection in single hepatocytes by developing single-cell laser capture microdissection (scLCM) and integrating this tool with highly sensitive quantitative real-time PCR. We reported that HCV infects a minority of hepatocytes that are found in geospatial clusters. More recently, we (PIs Balagopal and Thio) integrated scLCM with droplet digital PCR (ddPCR) to reveal the first observations of hepatitis B virus (HBV) infection at single cell resolution in the liver. We found that HBV infects nearly all hepatocytes prior to antiviral therapy. However, during antiviral therapy, HBV infection is diminished while viral transcription is markedly attenuated. Our lab has also focused on HIV-1 infection and immune activation for over a decade. Most recently, we have studied type 1 interferon responses to HIV-1 using RNA sequencing (RNAseq). Using this technology, we identified novel interferon-stimulated genes (ISGs) that are associated with HIV-1 restriction in vivo.