2017 Milstein Young Investigator Award Winner
2017 Milstein Young Investigator Award Winner

Ari B. Molofsky, Assistant Professor, Department of Laboratory Medicine, University of California San Francisco

Ari Molofsky received a BS in Molecular Biology from the University of Texas in 1999 and completed his MD/PhD at the University of Michigan in 2007.   His graduate thesis work explored macrophage recognition and response to intracellular pathogens, including work that helped define how inflammasomes recognize intracellular bacterial flagellin and induce pyroptotic cell death.  Dr. Molofsky continued his training at the University of California San Francisco, completing a clinical pathology residency and a post-doctoral fellowship with Dr. Richard Locksley.  His post-doctoral work helped elucidate the role of type 2 allergic immune cells in adipose tissue metabolism, including how eosinophils, group 2 innate lymphoid cells, regulatory T-cells, and the cytokine IL-33 control adipose tissue metabolism and protect against metabolic dysfunction and type 2 diabetes.  He established an independent research group at UCSF in 2015 with an appointment in the Department of Laboratory Medicine and affiliations with the UCSF Immunology Program and Diabetes Center.

Dr. Molofsky’s research lab is focused on the impact of tissue-resident lymphocytes in normal tissue development, remodeling, and the initiation of pathology.   The Molofsky lab studies how resident lymphocytes such as group 2 innate lymphoid cells (ILC2) and regulatory T cells (Treg) are supported at tissue niches, using a combination of advanced microscopy, genetic tools, and transcriptomics.   The lab has been studying the cellular sources and regulation of the cytokine IL-33, which potently activates ILC2 and Treg, in systemic metabolic function, allergic lung disease, and neurodevelopment.  They are also exploring how resident lymphocytes interact and compete at tissue niches to determine immunologic outcomes.  In addition to the Milstein Young Investigator award, Dr. Molofsky is the recipient of the Larry L. Hillblom Young Investigator Award, a career development award from the NIDDK, and a UCSF New Frontiers Research Award.

Abstract from Award’s Presentation at Cytokine 2017 in Kanazawa:

Defining group 2 innate lymphoid cell tissue niches
Ari B Molofsky
Dept. of Laboratory Medicine, UCSF, San Francisco, United States

Group 2 innate lymphoid cells (ILC2) are tissue resident cells that are key instigators of type 2 allergic immune responses. ILC2 can promote beneficial type 2 immunity in the context of helminth infection, but are also key contributors to the allergic pathology associated with asthma and atopic dermatitis. ILC2 are developmentally deposited in tissues where they locally proliferate, and recent work suggests their contribution to physiologic tissue responses during tissue development and tissue remodeling. Our group’s prior work indicates adipose tissue ILC2s are key coordinators of a mixed regulatory/type 2 immune response which promotes adipose tissue function and is protective in models of obesity and type 2 diabetes. However, the cells and signals that regulate ILC2 in tissues are only beginning to be explored. In adipose tissue and elsewhere, the IL-1 family cytokine IL-33 is a dominant positive regulator of ILC2 function. As such, we have pursued the regulation and cellular sources of IL-33 that are proximal to tissue-resident ILC2. Using high-resolution imaging and genetic approaches, our studies suggest ILC2 are maintained in specific micro-anatomic tissue niches that are defined by subsets of non-hematopoietic IL-33 expressing cells. By defining these ILC2 niches, we hope to better understand the cells and signals that regulate ILC2 so that we may ultimately exert control over both beneficial and pathologic type 2 immune responses.