Sergio Catz, PhD
Professor
Department of Molecular and Cellular Biology
Research Focus
Intracellular vesicular transport is essential for nearly all aspects of cellular physiology and plays a central role in the regulation of cellular homeostasis, cell division and immunity. The processes regulated by vesicular transport studied in my laboratory include autophagy, exocytosis, cytokine secretion, phagocytosis, nucleic acid sensing, neutrophil extracellular trap formation and lysosomal function. Molecular mechanisms studied in my laboratory are associated with human diseases including inflammation in the setting of coronary artery disease, lysosomal storage disorders and autoimmunity.
Most vesicular transport processes are regulated by Rab proteins, monomeric GTPases of the Ras superfamily, that act as membrane organizers. My laboratory utilizes super-resolution microscopy approaches and functional assays for the study of Rab GTPases and effector molecules and their role in trafficking mechanisms. In our studies, we utilize animal models and cellular systems with the common objective of elucidating cellular mechanisms important for physiology and disease. In addition, we have developed unique quantitative systems biology methods for the analysis of organelle dynamics and positioned ourselves as one of the few laboratories studying the processes that control vesicular trafficking mechanisms preceding exocytosis, phagocytosis, endosomal maturation and autophagolysosomal formation in innate immune cells.
We have developed and implemented high-throughput screening assays and identified small-molecule inhibitors and activators of vesicular trafficking. We discovered specific compounds that are being utilized to interrogate mechanistic questions and explore their activity in pre-clinical models of coronary artery disease, lysosomal disorders, viral encephalitis and autoinflammatory syndrome. Our research elucidates molecular mechanisms regulating vesicular transport and has the potential to lead to effective, novel therapeutical strategies for the treatment of human disease.
Select Publications
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Yu, Juan; Meneses-Salas, Elsa; Johnson, Jennifer L.; Manenti, Susanna; Kbaich, Mouad Ai A.; Chen, Danni; Askari, Kasra; He, Jing; Shukla, Aparna; Shaji, Binchu; Gonzalez-Quintial, Rosana; Croker, Ben A.; Zhang, Jinzhong; Hoffman, Hal; Kiosses, William B.; Hedrick, Catherine; Pestonjamasp, Kersi; Wineinger, Nathan; Baccala, Roberto; Catz, Sergio D. Defective endomembrane dynamics in Rab27a deficiency impairs nucleic acid sensing and cytokine secretion in immune cells. Cell Reports 2024, 43, 114598.
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Catz, Sergio D. Divergent mechanisms of inflammasome activation in neutrophil early response and inflammation. Nature Immunology 2023, 24, 1970-1971.
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Johnson, Jennifer A.; Meneses-Salas, Elsa; Ramadass, Mahalakshmi; Monfregola, Jlenia; Rahman, Farhana; Gontijo, Raquel C.; Kiosses, William B.; Pestonjamasp, Kersi; Allen, Dale J.; Zhang, Jinzhong; Osborne, Douglas; Zhu, Yanfang P.; Wineinger, Nathan E.; Askari, Kasra; Chen, Danni; Yu, Juan; Henderson, Scott C.; Hedrick, Catherine C.; Ursini, Matilde V.; Grinstein, Sergio; Billadeau, Daniel D.; Catz, Sergio D. Differential dysregulation of granule subsets in WASH-deficient neutrophil leukocytes resulting in inflammation. Nature Communications 2022.
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Johnson, Jennifer L.; Ramadass, Mahalakshmi; Rahman, Farhana; Meneses-salas, Elsa; Zgajnar, Nadia R.; Gontijo, Raquel C.; Zhang, Jinzhong; Kiosses, William B.; Zhu, Yanfang P.; Hedrick, Catherine C.; Perego, Marta; Gunton, Jenny E.; Pestonjamasp, Kersi; Napolitano, Gennaro; Catz, Sergio D. The atypical small GTPase GEM/Kir is a negative regulator of the NADPH oxidase and NETs production through macroautophagy. Journal of Leukocyte Biology 2021, 110, 629-649.
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Zhang, Jinzhong; Rahman, Farhana; Pestonjamasp, Kersi; Johnson, Jennifer L.; He, Jing; Cherqui, Stephanie; Catz, Sergio D. DYNC1LI2 regulates localization of the chaperone-mediated autophagy receptor LAMP2A and improves cellular homeostasis in cystinosis. Autophagy 2021, 18, 1108-1126.
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Zeng, Furong; Chen, Zhizhao; Chen, Rao; Shufesky, William J.; Bandyopadhyay, Mohna; Camirand, Geoffrey; Oberbarnscheidt, Martin H.; Sullivan, Mara L.; Baty, Catherine J.; Yang, Mu-qing; Calderon, Michel; Stolz, Donna B.; Erdos, Geza; Pelanda, Roberta; Brennan, Todd V.; Catz, Sergio D.; Watkins, Simon C.; Larregina, Adriana T.; Morelli, Adrian E. Graft-derived extracellular vesicles transported across subcapsular sinus macrophages elicit B cell alloimmunity after transplantation.. Science Translational Medicine 2021, 13, eabb0122.
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Catz, Sergio D.; McLeish, K. R. Therapeutic targeting of neutrophil exocytosis. Journal of Leukocyte Biology 2020, 107, 393-408.
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Karmakar, M.; Minns, M.; Greenberg, E. N.; Diaz-Aponte, J.; Pestonjamasp, K.; Johnson, J. L.; Rathkey, J. K.; Abbott, D. W.; Wang, K.; Shao, F.; Catz, Sergio D.; Dubyak, G. R.; Pearlman, E. N-GSDMD trafficking to neutrophil organelles facilitates IL-1 beta release independently of plasma membrane pores and pyroptosis. Nature Communications 2020, 11, 2212.
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