Project 1: Characterization of the immunometabolic drivers of granuloma formation

Tuberculosis is a highly complex disease, caused by Mycobacterium tuberculosis (Mtb). The complex interplay of alveolar cells, immune cells, and Mtb drives granuloma formation is schematically diagrammed in the figure. Granulomas are the pathological hallmark of TB and of the host's response to contain Mtb infection. The breakdown of the granuloma leads to the release and dissemination of infectious Mtb. As a result, understanding the precise immunometabolic processes that govern granuloma formation and function is crucial for developing better diagnostic tools, treatments, and vaccines. We are currently utilizing interdisciplinary approaches including microbiology, immunology, single-cell transcriptomics and metabolomics to approach this unique scientific problem.

Reference:

Parveen S, Murphy JR, and Bishai WR. (2021). Targeting inhibitory cells such as Tregs and MDSCs in the tuberculous granuloma. Springer Cham. (Book Chapter)

Project 2: Determine the role of bacterial and host glutamine metabolism in TB pathogenesis

Glutamine metabolism upregulation has been associated with several bacterial, viral, and oncogenic diseases, yet its role is poorly understood in TB pathogenesis. While host immune cells may limit Mtb's access to glutamine as part of the immune response, Mtb alters host glutamine metabolism, potentially affecting immune cell function and the overall immune response to infection. My research goal is to understand the precise mechasnim(s) of how the host and mycobacterial glutamine metabolism influences TB pathogenesis. These new findings will have the potential to define unique targets that may result in new approaches to contain TB by either disrupting bacterial nutrient acquisition or improving the functionality of the host immune response. 

References:

Parveen S* and Bishai WR (2024). Role of Glutamine metabolism in tuberculosis pathogenesis: A mini review. Frontiers in Tuberculosis (In Press) (*co-corresponding author) (Review)

Parveen S, Shen J, Lun S, Zhao L, Koleske B, Leone RD, Rais R, Powell JD, Murphy JR, Slusher BS, and Bishai WR (2023). Glutamine metabolism has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis. Nature Communications. PMID: 37973991 (Research Article)