Focus

The 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.

Research

Establishing niche-specific macrophage fates

Resident 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 dynamics

Following 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 dysfunction

Aged 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.

Biography

Kai Mesa is an Assistant Professor in the Department of Molecular Biology. Dr. Mesa started his training in 2008 at the University of California, Berkeley in the laboratories of Irina Conboy and David Zusman. He graduated in 2010 and moved to Yale University for his graduate work. There, advised by Valentina Greco, Dr. Mesa developed cutting-edge intravital imaging techniques to investigate the tissue dynamics and cellular mechanisms that maintain adult stem cells in the skin of living mice. He earned his PhD in 2017. Following graduate studies, Dr. Mesa joined the laboratory of Dan Littman at the New York University Skirball Institute, where he received postdoctoral fellowships from the Jane Coffin Childs Memorial Fund for Medical Research and the Charles H. Revson Foundation. His postdoctoral work pioneered new approaches to track the 3D spatial distribution and cellular turnover kinetics of resident macrophages during physiological aging. This work now provides a novel platform to comprehensively investigate immune cell trafficking dynamics and long-term fate decisions across various tissue regeneration and disease states in vivo. Dr. Mesa’s research interests center on how tissues dynamically coordinate immune and stem cell function during homeostasis, regeneration and aging.

Honors & Awards

• 2021 Charles H. Revson Senior Fellowship in Biomedical Science
• 2017 Jane Coffin Childs Postdoctoral Fellowship
• 2017 Carolyn Slayman Prize in Genetics, Yale University
• 2015 ASCB Beckman Coulter Distinguished Graduate Student Achievement Prize
• 2014 National Science Foundation Graduate Research Fellowship