Aaron DiAntonio, MD, PhD

Aaron DiAntonio, MD, PhD

Alan A and Edith L Wolff Professor of Developmental Biology

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Research interests

Our laboratory investigates molecular mechanisms that control the structure and function of neural circuits in health and disease. We combine genetic, molecular, neuroanatomical, and bioinformatic analyses to identify pathways that promote the maintenance of axons and synapses in neurodegenerative disease and aging. Our prior mechanistic insights have led to the development of a novel therapeutic currently in clinical trials. Our studies focus on three major areas:

Axon Degeneration: Defining Mechanisms and Developing Therapies

Axon loss drives morbidity and progression of many common neurological diseases including peripheral neuropathy, glaucoma, traumatic brain injury, multiple sclerosis, and neurodegenerative diseases such as Alzheimer’s Disease, Parkinson’s Disease, and ALS.

Axon degeneration is a genetically-encoded program of subcellular self-destruction. We use Drosophila, mice, and human iPSC-derived neurons to define the molecular mechanisms of the axon degeneration pathway.

We identified SARM1 as the central executioner of the axonal degeneration program and demonstrated that it is the founding member of an ancient class of enzymes that cleave the essential metabolite NAD.

Using these mechanistic insights, we have developed small molecule inhibitors and gene therapy approaches to block the SARM1 pathway that are currently in clinical development as potential therapies for neurodegenerative disease.

Neuroimmunology and Axon Glia Interactions

A comprehensive understanding of axon maintenance in health and disease requires dissecting the interactions between axons and the cellular components of the nerve such as glia, immune cells, and likely additional cell types including specialized fibroblasts and adipocytes. Our studies of neurodegeneration have highlighted the complex interplay among these cell types in the degenerative process.

We incorporate the latest single cell and spatial transcriptomic techniques with traditional genetic, metabolic, imaging, and pathological analysis to dissect the multicellular interactions within the nerve. We expect that insights will lead to the development of novel therapies targeting this cellular crosstalk.  

The TIR domain: A Novel Family of NAD Cleaving enzymes 

TIR domain proteins are an ancient family of NAD cleaving enzymes important for the intersection of metabolism, inflammation, and neurodegeneration.

The TIR domain is the canonical protein motif of innate immune signaling, previously defined only as a scaffold for organizing signal transduction cascades. Through our studies of SARM1, we discovered that the TIR domain is an enzyme that cleaves the essential metabolic co-factor NAD. We discovered that this ancient function of TIR domains is conserved in animals, plants, bacteria, and archaebacteria, thereby redefining our understanding of innate immune signaling across the domains of life.

We are exploring the role of TIR domain enzymes as central nodes for the integration of immune signaling, metabolism, and inflammation in neurodegenerative disease. 

Back row: Sylvia Johnson, Eddy J. Brace, Sarah Schurr, Lili Barbar, Aaron DiAntonio, James O’Connor, Laura Devault, Miko Kozlowski

Seated: Xiaolu Sun, Shweta Tendulkar, Lily Spatz, Kelsey Krus

Education and Training

Professor of Department of Developmental Biology, Washington University School of Medicine, 2010-present

Associate Professor Department of Developmental Biology, Washington University School of Medicine, 2005-present

Assistant Professor Department of Developmental Biology, Washington University School of Medicine, 1999-2005

Postdoctoral Fellow University of California at Berkeley, Department of Molecular and Cell Biology, 1995-1999. Postdoctoral Advisor: Dr. Corey Goodman

Ph.D. Stanford University School of Medicine, Department of Molecular and Cellular Physiology, 1989-1995. Thesis Advisor: Dr. Thomas Schwarz

M.D. Stanford University School of Medicine, 1989-1995

M. Phil. Cambridge University, Biochemistry, 1989

A.B. Harvard University, Biochemistry and Molecular Biology, 1984-1988

Honors and Awards

Spirit of Hope Award, Hope Happens, 2023

Chancellor’s Award for Innovation and Entrepreneurship, Washington University, 2021

AAAS Fellow, American Academy for the Advancement of Science, 2020

Javits Neuroscience Award, NIH, 2020

Alan A. and Edith L. Wolff Professor of Developmental Biology, 2014

Outstanding Faculty Mentor Award, Graduate Senate, Washington University, 2011

Outstanding Faculty Mentor Award, Postdoctoral Society, Washington University, 2008

Keck Distinguished Young Scholar, 2002-2007

McKnight Scholar Award, 2002-2004

Sloan Research Fellow, 2001-2003

Edward Mallinckrodt, Jr. Foundation Award, 2000-2003

Whitehall Foundation Award, 2000-2003

Burroughs Wellcome Career Award in the Biomedical Sciences, 1998-2003

Helen Hay Whitney Fellow 1996-1998

Damon Runyon-Walter Winchell Fellow, 1996

Hershel Smith Harvard Scholarship, Harvard College, 1988

Phi Beta Kappa, Harvard College, 1988

Selected recent publications: DiAntonio Lab

See a complete list of Dr. DiAntonio’s publications »