Sunny Shin

My lab is interested in uncovering innate immune mechanisms used by the host to defend itself against bacterial pathogens and how bacterial pathogens evade host immunity to cause disease. We study innate immunity and host:pathogen interactions using a variety of gram-negative bacteria. We study the intracellular bacterial pathogens Legionella pneumophila, Coxiella burnetii, and Salmonella Typhimurium, and the extracellular pathogen Yersinia pseudotuberculosis using mouse and human model systems with the goal of identifying shared and unique features of innate immunity and bacterial virulence in mice and humans. A major focus of our lab is to understand how the immune system distinguishes between virulent and avirulent bacteria and tailors appropriate antimicrobial responses. One key immune pathway involves the inflammasome, a multi-protein cytosolic complex that activates the host proteases caspase-1, mouse caspase-11, and human caspases-4 and -5 upon cytosolic detection of bacterial products. These caspases mediate the release of IL-1 family cytokines and other inflammatory factors critical for host defense, but overexuberant activation can lead to pathological outcomes such as septic shock. We are currently pursuing how inflammasomes and other cell death pathways are differentially regulated in humans and mice in response to bacterial infection. We are also interested in elucidating how the immune system successfully overcomes the ability of pathogens to suppress critical host functions. We recently found that infected macrophages circumvent Legionella's ability to block host translation by selectively synthesizing and releasing key cytokines. These cytokines then coordinate crosstalk between the alveolar epithelium and bystander immune cells to generate an effective immune response. We also found that dendritic cells undergo cell death in response to Legionella-mediated blockade of host translation. We aim to define additional mechanisms that the immune system uses to detect and overcome pathogen virulence activity to promote antimicrobial defense. Insight into these different areas will advance our understanding of bacterial pathogenesis, how the innate immune system distinguishes between virulent and avirulent bacteria and initiates antimicrobial immunity, and will ultimately aid in the design of effective antimicrobial therapies and vaccines.

Nataraj, N.M., Garcia Sillas, R., Herrmann, B.I., Shin, S.*, and Brodsky, I.E.*: Blockade of IKK signaling induces RIPK1-independent apoptosis in human macrophages. PLOS Pathogens 20(8): e1012469, 2024 Notes: *co-corresponding authors. Grayczyk, J.P.^, Liu, L.^, Egan, M.S., Aunins, E., Wynosky-Dolfi, M.A., Canna, S.W., Minn, A.J., Shin, S.*, Brodsky, I.E.*: TLR priming licenses NAIP inflammasome activation by immunoevasive ligands. Proc Natl Acad Sci U S A 121(48): e2412700121, 2024 Notes: ^co-first authors; *co-corresponding authors. Akuma, D.C.^, Wodzanowski, K.A.^, Schwartz Wertman, R.^, Exconde, P.M., Vázquez Marrero, V.R., Odunze, C.E., Grubaugh, D., Shin, S.*, Taabazuing, C.*, Brodsky, I.E.*: Catalytic activity and autoprocessing of murine caspase-11 mediate noncanonical inflammaso