Kai Mesa Position Assistant Professor of Molecular Biology Website Mesa Lab Email [email protected] Office Thomas Laboratory, 334 Bio/Description FocusThe Mesa lab studies macrophages, multitasking immune cells that engulf billions of dying cells everyday, fight invading pathogens, and orchestrate wound healing responses. Combining expertise in immunology, stem cell biology, and multiphoton microscopy, we investigate how context-specific macrophage fates dynamically shape tissue regeneration and physiological aging.ResearchEstablishing niche-specific macrophage fatesResident immune cells remain localized to distinct tissue niches and adopt unique functions to support local homeostasis. Selective loss of these niche-specific cells leads to inflammation and tissue dysfunction. Despite this fundamental insight, it remains unclear how these cells selectively establish a resident fate to contribute to local tissue health. Utilizing multiphoton intravital microscopy in the mouse skin, the lab aims to identify the sequence of cellular behaviors and molecular cues that drive immune cell recruitment and integration into a tissue niche.Wound-induced immune cell dynamicsFollowing tissue injury and immune cell recruitment, a tissue can either (1) form a scar or (2) regenerate the lost tissue structures. In mammalian skin, immune cells (including macrophages) can drive both scarring and regenerative outcomes. Therefore, the lab aims to identify the early tissue dynamics and molecular signals of immune cells that yield a permissive environment for regenerative outcomes, which can be leveraged to overcome current limitations in tissue regeneration.Local immune cell aging and tissue dysfunctionAged tissues contain dysfunctional immune cells that contribute to impaired wound healing and pathogen clearance. However, it remains unclear the source of these age-associated immunological defects. Do aged tissues drive immune cell dysfunction? Or do aged immune cells locally corrupt a tissue over time? To address these fundamental questions, I propose to leverage novel spatial transcriptomic approaches based on in vivo niche-specific fluorescent labeling in mammalian skin to unify immune cell transcription, location, and behavior as tissues progressively age.Honors & Awards2021 Charles H. Revson Senior Fellowship in Biomedical Science2017 Jane Coffin Childs Postdoctoral Fellowship2017 Carolyn Slayman Prize in Genetics, Yale University2015 ASCB Beckman Coulter Distinguished Graduate Student Achievement Prize2014 National Science Foundation Graduate Research Fellowship Education Ph.D., Yale UniversityB.S., University of California, Berkeley Selected Publications 1.Mesa K, O’Connor K, Ng C, Salvatore S, Littman D. Niche-specific macrophage loss promotes skin capillary aging. bioRxiv : the preprint server for biology. 2023;. PMCID: PMC10473701 1.Cockburn K, Annusver K, Gonzalez D, Ganesan S, May D, Mesa K, Kawaguchi K, Kasper M, Greco V. Gradual differentiation uncoupled from cell cycle exit generates heterogeneity in the epidermal stem cell layer. Nature cell biology. 2022;24(12):1692–1700. PMCID: PMC9729105 1.Kedmi R, Najar T, Mesa K, Grayson A, Kroehling L, Hao Y, Hao S, Pokrovskii M, Xu M, Talbot J, Wang J, Germino J, Lareau C, Satpathy A, Anderson M, Laufer T, Aifantis I, Bartleson J, Allen P, Paidassi H, Gardner J, Stoeckius M, Littman D. A RORγt cell instructs gut microbiota-specific T cell differentiation. Nature. 2022;610(7933):737–743. PMCID: PMC9908423 1.Mesa K, Kawaguchi K, Cockburn K, Gonzalez D, Boucher J, Xin T, Klein A, Greco V. Homeostatic Epidermal Stem Cell Self-Renewal Is Driven by Local Differentiation. Cell stem cell. 2018;23(5):677–686.e4. PMCID: PMC6214709 1.Rompolas P, Mesa K, Kawaguchi K, Park S, Gonzalez D, Brown S, Boucher J, Klein A, Greco V. Spatiotemporal coordination of stem cell commitment during epidermal homeostasis. Science (New York, N.Y.). 2016;352(6292):1471–4. PMCID: PMC4958018 1.Mesa K, Rompolas P, Greco V. The Dynamic Duo: Niche/Stem Cell Interdependency. Stem cell reports. 2015;4(6):961–6. PMCID: PMC4471832 1.Mesa K, Rompolas P, Zito G, Myung P, Sun T, Brown S, Gonzalez D, Blagoev K, Haberman A, Greco V. Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool. Nature. 2015;522(7554):94–7. PMCID: PMC4457634 Start Date January 16, 2025 Research Area Cell Biology, Development & Cancer Microbiology, Virology & Immunology