Immunology and Microbiology: Faculty Directory

The overall focus of the Pipkin lab is to elucidate how chromatin structure and transcription controls the gene expression programs that establish and maintain the differentiated states of T cells. The lab specifically studies how naïve CD8 T cells differentiate into effector and memory cytotoxic T lymphocytes (CTL). CTL are killer lymphocytes that hold outstanding promise for controlling viral infections and cancer therapeutically, as they can be employed in adoptive immunotherapy and are the target of successful vaccination. The Pipkin lab has developed novel approaches to map the fundamental repeating structures of chromatin (nucleosomes) at unprecedented resolution, novel reporter genes to track cells in vivo that induce expression of Prf1, an essential gene that is required for the anti-tumor killing activity of CTL, and the only systems to conduct genome-scale pooled RNAi screens in T cells, in vivo, during the course of actual viral infections. Using these tools and approaches, the Pipkin lab is clarifying how transcription factors govern the specific organization of nucleosomes that enforces CTL differentiation, identifying the chromatin regulatory factors that maintain the differentiated state epigenetically, and demonstrating how these processes mediate durable immunity.

The underlying theme of the research performed in the Solt laboratory is to understand the biologically relevant roles of nuclear receptors, a superfamily of ligand regulated transcription factors, in the immune system. Our lab uses a combination of molecular biology, genetic, and chemical biology approaches coupled with mouse models of autoimmunity and chronic inflammation to study how different nuclear receptors’ expression, function, and activity affects disease. As ligand-regulated transcription factors, nuclear receptors are excellent therapeutic targets for the treatment of a variety of diseases. Therefore, we also work in collaboration with medicinal chemists to develop small molecule ligands to these receptors to further probe their function in vitro and in vivo. Each receptor is unique and can have ligand- and/or tissue-specific effects. Thus, we aim to gain a better understanding of nuclear receptor activity in tissue and disease-specific contexts to determine their therapeutic potential and for more rational drug design.

According to the latest statistics published by the UNAIDS/WHO in 2021, 38.4 million people were living with the Human Immunodeficiency Virus (HIV), and 40.1 million have died as a result of HIV. Although antiretroviral drugs have had a dramatically beneficial impact on HIV-infected individuals who have access to treatment, they have had a negligible impact on the global epidemic. Therapies for retroviral infections now used in clinical practice have limitations in that they often only shorten the duration of disease symptoms but fail to completely eradicate the virus with viral replication and disease recurring after discontinuation of the drug therapy. Additionally, the emergence of HIV variants with drug-resistance is an ongoing clinical problem. Clearly having a larger repertoire of therapeutic agents would be beneficial for combating the HIV epidemic.

Retroviruses, due to their limited genome size and content, require the assistance of multiple host cellular proteins at each step in their elaborate replication cycle. Host cells, in response, have evolved many mechanisms for inhibiting viral replication. We have taken a general approach to identify the molecular interactions occurring within a cell that are critical for viral replication, or genes that have evolved in mammalian cells to regulate viral replication. The discovery of cellular factors involved in retroviral replication and our increased knowledge of their mode of action may leverage novel antiviral approaches in clinical settings as one could block the modified use without affecting cell viability.

I am interested in developing practical immune interventions against globally relevant human pathogens. HIV is the current topic of my research. My group is using rhesus macaque models of HIV/AIDS to develop active and passive immunization strategies for preventing and treating HIV infection.