Jason Vevea

Email: jvevea@wisc.edu

Vevea headshot 2021


Postdoctoral Fellowship Neuroscience, University of Wisconsin, Madison, WI
Ph.D. Pathobiology & Molecular Medicine, Columbia University, New York, NY
M.Phil. Pathobiology & Molecular Medicine, Columbia University, New York, NY
M.A. Pathobiology & Molecular Medicine, Columbia University, New York, NY
B.Sc. Biochemistry and Microbiology, University of Minnesota, Minneapolis, MN

Awards and Funding

Warren Alpert Foundation Distinguished Scholars Fellowship, 2020-2022

NIH Postdoctoral F32 Fellow, 2017-2020
Mentor: Dr. Edwin R Chapman
Program coordinator: Dr. Glen Nuckolls, grant # F32NS098604

F1000 Associate Faculty Member Travel Grant for Cell Biology Faculty, 2017

HHMI Med into Grad Program, 2010-2011
Clinical Mentor: Michio Hirano, M.D.

Professional Associations

Society for Neuroscience 2019-Present

F1000 Associate Faculty Member 2016-Present

Research Summary

Post-doc research

1. For my postdoctoral work, I sought to learn molecular neuroscience and create tools to help researchers address difficult questions. During this time, I focused on clarifying the roles of two presynaptic synaptotagmins (SYT) in the synaptic vesicle cycle. Interestingly, two SYTs (SYT1 and SYT7) have roles in synaptic vesicle (SV) docking and priming. Synaptotagmin 7 (SYT7) is a high affinity presynaptic protein that I found promotes activity dependent docking of SVs from its location on the axonal plasma membrane. Strikingly, the accumulation of SYT7 on the axonal membrane is dependent on g-secretase processing and palmitoylation. Identifying SYT7 as a g-secretase substrate highlights the importance of this protein in human disease. Another synaptotagmin, SYT1, is a low affinity presynaptic protein that appears to have multiple debated roles in the SV cycle. Because synapses are highly plastic, chronic disruption of synaptic proteins can trigger homeostatic plasticity and obscure true phenotypes. I developed a method called knockoff to acutely disrupt long-lived membrane bound proteins and mitigate this complicating factor. Using knockoff, I found that loss of SYT1 resulted in an ‘unclamping’ of SVs. The rate of SYT1 protein degradation using knockoff was mirrored by 1) the rate of loss of synchronous SV release, and 2) the rate of increased spontaneous release. Therefore, SYT1 serves a dual function as a Ca2+ sensor for rapid synchronous release and as a clamp that inhibits spontaneous release under resting conditions. This method is generalizable and should be applicable to the many long-lived membrane bound proteins at the presynapse.

a. Vevea, J. D., Kusick, G. F., Chen, E., Courtney, K. C., Watanabe, S. & Chapman, E. R. (2021). Synaptotagmin 7 is targeted to the axonal plasma membrane through γ-secretase processing to promote synaptic vesicle docking in mouse hippocampal neurons. Elife (in press); bioRxiv (https://doi.org/10.1101/2021.02.09.430404).

b. Vevea, J. D. & Chapman, E. R. (2020). Acute disruption of the synaptic vesicle membrane protein synaptotagmin 1 using knockoff in mouse hippocampal neurons. Elife, 9, p.e56469.


Rat hippocampal dendrites @ 21 DIV expressing iGluSnFR

Graduate research

2. In Dr. Liza Pon’s lab during graduate school, I focused my research interests on mechanisms governing mitochondrial inheritance and cellular fitness using Saccharomyces cerevisiae as a model. After identifying mitochondrial inheritance as a key regulator of lifespan, I examined published synthetic genetic arrays (SGAs), and was able to identify negative genetic interactions between genes involved with lipid biosynthesis and mitochondria and ER dynamics and homeostasis. In response to impaired phosphatidylcholine biosynthesis, yeast exhibit broad organelle trafficking defects, specifically related to mitochondria and the ER. These organelles normally cooperate during lipid biosynthesis. We found that while mitochondrial dynamics and localization were impacted, mitochondria maintained normal function. We examined the ER and found markers related to misfolded protein stress and an accumulation of lipid droplets (LDs). The creation and destruction of LDs was critical for recovery of cellular health. During these studies we learned of a human congenital muscular dystrophy (CMD) caused by impaired phosphatidylcholine biosynthesis (CHKB CMD). This connection was a direct product from my ‘Med into Grad’ training and clinical mentorship from Dr. Michio Hirano. This disease presents clinically as early onset muscle wasting, cardiomyopathy, a severe mental handicap, with mitochondrial enlargement and mislocalization in muscle biopsies. Our results from yeast led us to speculate that mitochondria may not the only defect in this CMD. We investigated SR localization in patient samples and found the SR to be disorganized as well. We then investigated calcium handling in the mouse model for this human CMD. We found evidence for altered calcium dynamics in the form of calcium sparks mediated through dysfunctional RyR calcium channels in dystrophic muscle fibers but not littermate control muscle fibers. These observations provide clinically testable hypotheses through modulation of RyR function by available small molecule RyR modulators and this work is currently ongoing.

a. Garcia, E. J., Vevea, J. D., & Pon, L. A. (2018). Lipid droplet autophagy during energy mobilization, lipid homeostasis and protein quality control. Frontiers in bioscience (Landmark edition), 23, 1552.

b. Vevea, J. D., Garcia, E. J., Chan, R. B., Zhou, B., Schultz, M., McCaffery, J. M., Di Paolo, G. & Pon, L. A. (2015). Role for lipid droplet biogenesis and microlipophagy in adaptation to lipid imbalance in yeast. Developmental Cell 2015:35.5, 1-16

c. Vevea, J. D., Swayne, T. C., Boldogh, I. R., & Pon, L. A. (2014). Inheritance of the fittest mitochondria in yeast. Trends in cell biology, 24(1), 53-60. This is a featured review article.

d. McFaline‐Figueroa, J. R.*, Vevea, J.*, Swayne, T. C., Zhou, C., Liu, C., Leung, G., Boldogh, I. R. & Pon, L. A. (2011). Mitochondrial quality control during inheritance is associated with lifespan and mother–daughter age asymmetry in budding yeast. Aging cell, 10(5), 885-895. *These authors contributed equally to the manuscript.


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