Aaron DiAntonio
Professor

Departments of Developmental Biology
and Neurosciences

Developmental Biology and
Molecular Genetics Programs

Department of Developmental Biology
Washington University School of Medicine
Campus Box 8103
660 South Euclid Avenue
St. Louis, MO 63110
(314) 362-9925
diantonio@wustl.edu

Developmental Biology Program Website (click here)
Neuroscience Program

Research Interests

Our laboratory investigates molecular mechanisms that control the structure and function of neural circuits in development and disease. We combine genetic, molecular, neuroanatomical, and electrophysiological studies in both Drosophila and mouse to identify pathways required for the development, maintenance, and regeneration of axons and synapses. Our studies focus on three major areas:
1) Axonal degeneration in disease: Axonal degeneration is a common feature of many neurological diseases including hereditary neuropathies, diabetes, glaucoma, chemotherapy-induced neurotoxicity, and neurodegenerative diseases such as Alzheimer's and Parkinson's. Axonal degeneration is an active process of self-destruction that appears to be naturally primed and waiting for a triggering stimulus that activates the execution phase. We identified the DLK/JNK MAP kinase pathway as the first intrinsic neuronal pathway that promotes axonal degeneration following injury. We are using genome-wide screens in both Drosophila and mice to identify the molecular mechanisms driving axonal degeneration. Identifying and characterizing components of the intrinsic axonal degeneration pathway has identified potential therapeutic targets for the many neurological diseases characterized by axonal degeneration.

2) Axonal regeneration in response to injury: Neuronal repair is greatly impaired by the failure of adult CNS neurons to regenerate axons lost to injury or disease. Remarkably, a prior preconditioning injury can activate an axonal growth program and promote axonal regeneration. We have recently demonstrated that the MAPKKK DLK is a key trigger that induces this preconditioning response. We are investigating the mechanisms by which this regenerative growth program can be activated in order to promote neuronal repair. Finally, we are using high-content automated screening approaches to undertake large-scale drug and RNAi screens in order to identify novel therapeutic candidates that induce axonal regeneration.

3) Synaptic function: Neurotransmitter is released from the presynaptic cell at specialized sites called active zones. Efficient synaptic transmission requires that active zones contain a normal complement of proteins, and that these specialized release sites be apposed to postsynaptic clusters of neurotransmitter receptor. Little is known of the molecular mechanisms that regulate the protein composition of active zones and ensure the alignment of neurotransmitter release and reception machinery. Using large-scale genetic screens in Drosophila we are uncovering the molecular mechanisms that form and maintain the active zone/receptor cluster dyad.

Biosketch

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

• 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
• Howard Hughes Medical Institute, Faculty Development Award, 2000-2002
• McDonnell Center Grant, 2000-2001
• Burroughs Wellcome Career Award in the Biomedical Sciences, 1998-2003
• Helen Hay Whitney Fellow 1996-1998
• Damon Runyon-Walter Winchell Fellow, 1996
• Medical Scientist Training Program Fellow, 1989-1995
• Hershel Smith Harvard Scholarship, Harvard College, 1988
• Phi Beta Kappa, Harvard College, 1988

Selected Publications

Shin, J.E., Cho, Y., Beirowski, B., Milbrandt, J., Cavalli, V., and DiAntonio, A. (2012) Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration. Neuron 74: 1015-1022

Valakh, V., Naylor, S.A., Berns, D.S., and DiAntonio, A. (2012) A large-scale RNAi screen identifies functional classes of genes shaping synaptic development and maintenance. Dev. Biol. 366: 163-171.

Kim, S., Naylor, S.A., and DiAntonio, A. (2012) Drosophila Golgi membrane protein Ema promotes autophagosomal growth and function. P.N.A.S. 109: E1072-1081.

Bhattacharya M.R.C., Gerdts J., Naylor S.A., Royse E., Ebstein S.Y., Sasaki Y., Milbrandt J., and DiAntonio A. (2012) A Model of Toxic Neuropathy in Drosophila Reveals a Role for MORN4 in Promoting Axonal Degeneration. J. Neuroscience 32: 5054-5061.

Graf ER, Heerssen HM, Wright CM, Davis GW and DiAntonio A. Stathmin is Required for Stability of the Drosophila Neuromuscular Junction. J. Neuroscience 2011 31: 15026-34.

Tian X, Li J, Valakh V, DiAntonio A and Wu C. Drosophila Rae1 controls the abundance of the ubiquitin ligase Highwire in post-mitotic neurons. Nature Neuroscience 2011 14: 1267-75.

Vohra BPS, Sasaki Y, Miller BR, Chang J, DiAntonio A and Milbrandt J. Amyloid Precursor Protein Clevage-Dependent and –Independent Axonal Degeneration Programs Share a Common Nicotinamide Mononucleotide Adenylyltransferase Sensitive Pathway. J. Neuroscience 2010 30: 13729-13738.

Graf ER, Daniels RW, Burgess RW, Schwarz T and DiAntonio A. Rab3 Dynamically Controls Protein Composition at Active Zones. Neuron 2009 64: 663-677.

Miller RB, Press C, Daniels RW, Sasaki Y, Milbrandt J and DiAntonio A. A DLK-dependent axon self-destruction program promotes Wallerian degeneration. Nature Neuroscience 2009 12: 387-389.

Bloom AJ, Miller BR, Sanes JR and DiAntonio A. The requirement for Phr1 in CNS axon tract formation reveals the corticostriatal boundary as a choice point for cortical axons. Genes and Development 2007 21: 2593-2606.

Last Updated: 8/14/2012 4:44:33 PM