Joshua Farr

My research program is centered on defining how cellular senescence and the senescence-associated secretory phenotype (SASP) causally drive tissue dysfunction, pathological remodeling, and resistance to therapy across chronic diseases, and on leveraging this biology to develop rational, disease-modifying interventions. A central theme of my work is that senescent cells represent active and targetable mediators of disease progression rather than passive end states of cellular stress. For more than 14 years, I have led independent mechanistic and translational studies investigating senescence in vivo using complementary mouse models and human clinical samples. My laboratory has particular expertise in identifying, validating, and functionally interrogating senescent cell populations within the bone and vascular microenvironments, where metabolic stress, aging, and therapeutic injury converge. Through this work, I have established causal roles for senescent cells in skeletal fragility, impaired tissue repair, and pathological remodeling in settings that include metabolic disease, cancer therapy, and aging. A major focus of my research is translating senescence mechanisms into therapeutic strategies. I co-led the development and validation of SenMayo, a senescence gene expression signature that robustly identifies senescent cells across tissues and species and is responsive to genetic or pharmacologic senescent cell clearance. I also co-led a randomized controlled clinical trial demonstrating that intermittent senolytic therapy favorably modulates tissue remodeling in humans, providing direct proof-of-concept that targeting senescent cells is feasible and biologically effective in clinical settings. I joined the faculty of the University of Arizona Department of Medicine (Division of Rheumatology) and the Arizona Arthritis Center in August 2024 after 14 years at the Mayo Clinic, where I led foundational studies linking senescence to disease-relevant structural and functional outcomes. My laboratory now extends these discoveries into multiple preclinical disease models to define when and where senescent cells arise, how SASP signaling and senescence propagation contribute to tissue dysfunction or therapeutic resistance, and whether selective senescent cell elimination can be used to enhance durable treatment responses. In the proposed studies, I provide leadership in experimental design, senescence detection and validation, SASP profiling, and senolytic intervention strategies. By integrating molecular, histologic, and pharmacologic approaches, my work establishes senescence as a unifying, targetable mechanism underlying diverse chronic pathologies and positions me to lead studies that accelerate translation of senescence-targeted therapies into clinically meaningful outcomes.