SARM1 is the key executioner enzyme for axon degeneration. In a healthy neuron, SARM1 exists in an enzymatically “off” state. Axon injury turns on SARM1’s activity to hydrolyze the important metabolite NAD+, leading to metabolic crisis and axon fragmentation. The mechanism underlying SARM1 activation by axon injury was discovered in a recent study from the […]
Axons contain a protein, Sarm1, capable of triggering their self-destruction. It is crucial that such a protein be kept in an ‘off’ state or neurodegeneration will occur. In the current paper from the DiAntonio and Milbrandt labs at Washington University and the Hao Wu lab at Harvard University, Multiple domain interfaces mediate SARM1 autoinhibition, they […]
Dr. Aaron DiAntonio is being honored with fellowship in the American Academy for the Advancement of Science (AAAS) for his contributions to neuroscience, in particular to understanding pathways of injury response and degeneration in axons. Dr. DiAntonio is one of seven Washington University faculty named to the AAAS. Look for the formal announcement of the […]
Congratulations to Margaret Hayne for winning the Rita Levi-Montalcini Award for Best Student Presentation at the joint Developmental Biology/Developmental, Regenerative and Stem Cell Biology Virtual Retreat!
In a move that we hope will lead to faster development of therapies targeting Sarm1 in neurodegenerative diseases, Eli Lilly bought Disarm Therapeutics, the company cofounded by Aaron and Jeff. The Source has a nice write-up covering the Disarm’s founding and acquisition.
In July, Dr. Frey joined Serepta Therapeurtics as Senior Manager, Project Management Gene Therapy Research.
We would like to wish Lauren Walker, a former graduate student in the lab, a hearty congratulations for winning the best talk prize at the Hilde Mangold Postdoctoral Symposium at the recent Society for Developmental Biology meeting. She won the award for her presentation on “Identification of extrinsic cues promoting target-selective axon regeneration”.
In March, like many labs across the country, we reduced activity in the lab to a bare minimum in order to protect our members and the larger community. We rapidly accustomed ourselves to lab meetings held via Zoom. Intrepid graduate student Mikolaj Kozlowski pioneered the virtual rotation, later joining the lab. Postdoc Kwang Woo Ko […]
A recent JCB paper from postdoc Kwang Woo Ko looks at Sarm1’s role in glaucoma. He shows that knocking out Sarm1 protects retinal ganglion cells and axons in a mouse model of glaucoma. His experiments demonstrate that neuroinflammatory and necroptotic signaling work through SARM1 to drive axon loss.
Hailun “Helen” Li successfully defended her thesis work with a polished presentation via Zoom on April 9th, the first ever virtual thesis defense in the lab. Her work has opened up a new area of interest for the lab, looking at the roles of Sik3 and HDAC4 in regulation of potassium levels in the nerve […]
We are extremely pleased to have several new members in 2019. John Palucki joined the lab as a research technician and is helping with many of the tissue culture experiments. Kelsey Krus and Jayson Cruz are both neuroscience graduate students in WUSM’s Medical Scientist Training Program. We are also pleased to welcome Dr. Laura Devault, […]
Dr. Aaron DiAntonio and Dr. Jeffrey Milbrandt, co-directors of the Needleman Center for Axonal Therapeutics and Neurometabolism, launched the new center with a symposium featuring Aaron’s PhD mentor, Dr. Thomas Schwarz. Dr. Schwarz, who is now a professor at Harvard, gave a talk titled “Moving and Removing Neuronal Mitochondria”. Other speakers included Dr. Ghazal Ashrafi, […]
Previous work by Dr. Stefanie Geisler had shown that axonal damage subsequent to administration of vincristine, a common chemotherapeutic, was a result of a Sarm1-dependent mechanism. In the recent JCI Insight paper titled “Vincristine and bortezomib use distinct upstream mechanisms to activate a common SARM1-dependent axon degeneration program,” Dr. Geisler and colleagues demonstrated that Bortezomib, […]
Exciting new research from Alex Russo is presented this month in Cell Reports in a paper titled Wnd/DLK Is a Critical Target of FMRP Responsible for Neurodevelopmental and Behavior Defects in the Drosophila Model of Fragile X Syndrome. FMRP1 is the gene mutated in Fragile-X syndrome. It functions as a translational repressor that targets many mRNAs. When […]
Biology can be pretty amazing. A grad student in the Milbrandt lab, Kow Essuman, and collaborators at UNC and Colorado State University just published a paper in Science on the role of TIR domains in plants. The DiAntonio and Milbrandt labs study how axons degenerate after injury and in disease. A few years ago the […]
Aaron’s recent review in the journal PAIN synthesizes recent developments in our understanding of axon degeneration and discusses the therapeutic implications. This review also includes an audio recording of him describing the research progress. One of the key discoveries discussed is that Sarm1 is itself an NADase enzyme. Understanding that opens up new possibilities for pharmacological […]
On April 22, Dr. DiAntonio will kick off the Hope Center’s upcoming seminar series, Modeling Neurological Disorders Using Stem Cell-based Approaches. His talk is titled “Axon Degeneration: Mechanistic Insights Yield New Therapeutic Strategies for Neurodegenerative Diseases” and will be at noon in Holden Auditorium.
Alex will share her thesis work March 27, 2019 in a presentation titled “Neuronal stress pathways influence synaptic development and nervous system function in Drosophila melanogaster”. The seminar will be at 2pm in Holden Auditorium.
Read the review of Dr. Stefanie Geisler’s recent study in mice of preventing peripheral neuropathy with gene therapy. The article can be found here: https://www.foundationforpn.org/2019/01/22/gene-therapy-blocks-peripheral-nerve-damage-in-mice/
Dr. Susan Culican, a former clinical research fellow in the lab, has accepted a new position as Associated Dean of Graduate Medical Education at the University of Minnesota. Our congratulations and best wishes to her in this new endeavor.
New work from Alex Russo and others looking at the axon protective effects of Highwire’s interaction with dNMNAT will be published soon in EMBO Reports.
A new paper in the Journal of Experimental Medicine details the experiments led by Dr. Stefanie Geisler in collaboration with the Milbrandt and DiAntonio labs to target SARM1 using gene therapy in mice. This is an exciting step towards possible treatments for peripheral neuropathy and other disorders involving axon breakdown.
Aaron DiAntonio will be co-chairing the Neural Development and Neurodegeneration Symposium at the American Society for Cell Biology Meeting in San Diego, CA on December 10th, 2018.
We are pleased to have our recent paper looking at the role of TRPV1 in preconditioning the regeneration of DRG neurons reviewed as a “Featured Finding” by eNeuro.
Scott Karney-Grobe thesis work has been published in the PNAS paper, HSP90 is a chaperone for DLK and is required for axon injury signaling. This is an intriguing new role for Hsp90.
Hailun “Helen” Li has won the Thach Award for her short talk at the Annual Neuroscience Retreat. No one in the lab was surprised as even Helen’s lab meeting presentations are works of art, but we are especially happy as this is the second year in a row that a member of the lab has won. […]
We are proud to announce that Dan Summers, a postdoc with a joint appointment in the DiAntonio and Milbrandt labs, has a new paper in the Proceedings of the National Academy of Sciences journal titled Palmitoylation enables MAPK-dependent proteostasis of axon survival factors.
A look back at the lab folks circa 2002.
After a successful postdoc culminating with the publication of her eNeuro paper, TRPV1 Agonist, Capsaicin, Induces Axon Outgrowth after Injury via Ca2+/PKA Signaling, Dr. Frey accepted a Project Manager position at Folio Conversant, a contract research company in her hometown of Columbus, Ohio. This move gets two thumbs up from Erin. We’ll all miss her and wish […]
Congratulations to Dr. Scott Karney-Grobe who successfully defended his thesis! His work looked at the role of the chaperone protein Hsp90 in neural regeneration. We decided his celebratory cake needed a chaperone, too.