Jason Shepherd

Jason Shepherd

Dr. Jason Shepherd. Photo by Azeddine Tahiri

Jason Shepherd, Ph.D.

Assistant Professor of Neurobiology and Anatomy,
Biochemistry​ and Ophthalmology & Visual Sciences
University of Utah, School of Medicine

Contact Information

4539 Sorenson Molecular Biotechnology Building
36 S. Wasatch Dr. Salt Lake City, UT 84112

Office: 801-585-6214
Laboratory:  801-585-0926
Email:    jason.shepherd@neuro.utah.edu

A Word from Jason Shepherd

B rains have an amazing ability to learn and store information for long periods – in some cases, a lifetime. A major challenge in neuroscience is to understand how neuronal networks are sculpted by experience and how proteins/genes contribute to circuit modification. The goal of our research is to understand information storage, from the molecular level through in vivo neuronal networks and how these processes go awry in neurological disorders. My lab utilizes coordinated biochemical, cell biological, electrophysiological and imaging studies both in vitro and in vivo.

We recently discovered a novel mechanism of neuronal communication that resembles the life-cycle of retroviruses (https://www.sciencedirect.com/science/article/pii/S0092867417315040) . The neuronal gene Arc, a master regulator of synaptic plasticity and memory, contains a Gag retroviral homology domain that has conserved secondary structure with HIV-1 that is derived from a distinct family of retrotransposons. Arc protein self-assembles into viral-like capsids that are released from cells and carry RNA/proteins to neighboring cells. Our findings open up a new area of investigation in the cell biology of cell-to-cell communication, by revealing that some retrotransposon-derived genes retain the ability to form capsids that shuttle RNAs and proteins between cells. Ongoing projects in the lab aim to dissect this new intercellular pathway that intersects diverse fields of biology that include virology, extracellular communication, evolutionary biology, gene delivery and neuroscience.

Other projects in the lab include:

The synaptic engram – how networks of cells encode, store and retrieve information

How experience sculpts the brain, using in vivo 2-photon imaging in the visual cortex

The synaptic dysfunction that underlies neurological disorders, including Alzheimer’s Disease and autism spectrum disorders

Trafficking of neurotransmitter receptors at synapses

More about Jason Shepherd

Positions
  • January 2013 – Present. Assistant Professor, Department of Neurobiology and Anatomy. The University of Utah, School of Medicine. Salt Lake City, UT. USA.
  • April 2011 – December 2012. Postdoctoral Fellow (K99 award). The Picower Institute for Learning and Memory, Massachusetts Institute of Technology. Cambridge, MA. USA.
  • June 2007- April 2011. Howard Hughes Medical Institute Postdoctoral Fellow. The Picower  Institute for Learning and Memory, Massachusetts Institute of Technology. Cambridge, MA. USA.
Education
  • Jan 2003 – May 2007. Cellular and Molecular Medicine Graduate Program (Ph.D). The Johns   Hopkins School of Medicine. Baltimore, MD. USA.
  • Jan-Oct 2002. One year in the Neurobiology and Behavior Graduate Program as an   Exchange Abroad Scholar (counted towards undergraduate degree) University of   California, Irvine. Irvine, CA. USA.
  • 1999 – 2002. Bachelor of Science with First Class Honours in Neuroscience. University of   Otago. Dunedin, New Zealand.
  • 1998. American Field Scholar (AFS) Intercultural Exchange in Switzerland, Kantonschule   Trogen. Trogen, Appenzellerland. Switzerland
Academic Awards
  • NIH Collaborative Development Award: Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking and Assembly of HIV (CHEETAH), 2017
  • Kavli Fellow. Frontiers in Science, National Academy of Sciences, 2016
  • E. Matilda Ziegler Foundation for the Blind, Young Investigator Award, 2016
  • Angelman Syndrome Foundation Research Grant, 2013
  • NIH Pathway to Independence (PI) Award (K99/R00) from NINDS, April 2011.
  • International Society for Neurochemistry Young Investigator Award, 2011.
  • Peter and Patricia Gruber International Research Award in Neuroscience, 2010.
  • Keystone NIH Symposia Scholarship, 2010.
  • Swiss Society for Neuroscience FENS Travel Fellowship, 2008.
  • Howard Hughes Medical Institute Postdoctoral Fellowship, 2007.
  • The Paul Erlich Young Investigator Award, Johns Hopkins University School of Medicine, 2006.
  • Awarded Grass Foundation Fellowship in Neuroscience. Marine Biological Laboratory,   Woods Hole. Summer 2006.
  • Glenn/AFAR Scholarship for Research in the Biology of Aging, 2003.
  • Howard Hughes Predoctoral Fellowship, Honourable Mention, 2003.
  • University of Otago Neuroscience Prize, 2002 – awarded for the top Honours research thesis   in the undergraduate neuroscience program.
  • University of Otago Science Honours Scholarship, 2002 – awarded to the top ten Honours   theses in the Division of Science.
  • Exchange Abroad Scholarship, University of Otago/University of California Irvine, 2002.
  • Summer Research Fellowship, Research School of Biological Sciences, Australian National
  • University, 2001.
  • Summer Research Scholarship, School of Biological Sciences, University of Auckland, 2000.
Research Experience
  • July 2007- December 2012. Postdoctoral Research.Laboratory of Dr Mark Bear. Investigating the in vivo role of Arc in visual cortex plasticity. The Picower Institute for Learning and Memory, Massachusetts Institute of Technology. Cambridge, MA.
  • Summer 2009. Imaging Structure and Function in the Nervous System course. Cold Spring Harbor Laboratory, NY.
  • Summer 2006. Independent Research, Marine Biological Laboratory. The role of BCL-2 family proteins and mitochondrial function in post-synaptic transmission and plasticity. In collaboration with Elizabeth Jonas and Len Kaczmarek (Yale University). Woods Hole, MA.
  • Jan 2003 – May 2007. Doctoral Research. Laboratories of Dr Richard Huganir and Dr. Paul Worley. Investigation into the physiological function of the immediate early gene Arc and its role in AMPA receptor trafficking and synaptic dysfunction. Department of Neuroscience. Johns Hopkins School of Medicine. Baltimore, MD.
  • March-Oct 2002. Undergraduate Honours Thesis Research. Laboratory of Dr. Frank Laferla. Synaptic plasticity in novel transgenic models of neurodegeneration. Department of Neurobiology and behavior, University of California. Irvine, CA.
  • Jan-March 2002. Undergraduate Research Assistant. Laboratory of Dr. Oswald Steward. Cloning of the Dendrin 3’ UTR region for mRNA localization studies in neurons. Department of  Neurobiology and Behavior, University of California. Irvine, CA.
  • Nov-Dec 2001. Undergraduate Summer Research Scholarship. Laboratory of Dr. Ryszard Maleszka. RNA interference in cultured honeybee neurons. Research School of Biological Sciences, Australian National University. Canberra, Australia.
  • Nov 2000 – Feb 2001. Undergraduate Summer Research Scholarship. Laboratory of Dr. Garth Cooper. New therapies for Diabetic cardiomyopathy in streptozotocin rats. School of Biological Sciences, University of Auckland. Auckland, New Zealand.
  • March- August 2000. Undergraduate Research Assistant. Laboratory of Dr Mike Colombo. The involvement of the hippocampus in visual contextual memory in pigeons. Department of Psychology, University of Otago. Dunedin, New Zealand.
Publications
  • Wall M.J., Collins D.R., Chery S.L., Allen Z.D., Pastuzyn E.D., Nikolova V.D., Moy S.S., Philpot B.D., Shepherd J.D., Müller J., Ehlers M.D., Mabb A.M., Corrêa S.A.L. The temporal dynamics of Arc expression regulates cognitive flexibility. Neuron, 2018 May 24. pii: S0896-6273(18)30384-2
  • Shepherd J.D. Arc – An endogenous neuronal retrovirus? Seminars in Cell & Devopmental Biology. 2018 May;77:73-78. doi: 10.1016/j.semcdb.2017.09.029. Epub 2017 Sep 24.
  • Pastuzyn E.D., Day C.E., Kearns R.B., Kyrke-Smith M., Taibi A.V., McCormick J., Belnap D.M., Yoder N., Erlendsson S., Morado D.R., Briggs J.A.G., Feschotte C. and Shepherd J.D. The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer. Cell, 2018 Jan 11;172(1-2):275-288.e18.Cell Preview F1000 Prime recommended.PRESS and HIGHLIGHTS: The Atlantic, Yahoo News, Newsweek, Nature, IFL Science, Alphr, New Scientist, Spektrum der Wissenschaft, Inverse, Science Daily, Infosurhoy, Technology Networks, Biotechniques, BigThink, SciShow, NIH, CNRS
  • Jenks K.R., Kim T., Pastuzyn E.D., Okuno H., Taibi A.V., Bito H., Bear M.F., Shepherd J.D. Arc restores juvenile plasticity in adult mouse visual cortex. PNAS, 2017 Aug 22;114(34):9182-9187.PRESS: Medical News Today, Deseret News, Science Daily, SciCast, Medical Xpress, Genetic Engineering News, Daily Mail
  • Pastuzyn E.D. and Shepherd J.D. Arc-dependent Homeostatic Synaptic Plasticity Is Altered in Angelman Syndrome Model Mice. Frontiers in Molecular Neuroscience, 2017 Jul 28;10:234.
  • Kim G., Nagarajan N., Pastuzyn E.D., Jenks K.R., Capecchi M., Shepherd J.D., Menon R. Deep-brain imaging via epi-fluorescence Computational Cannula Microscopy. Sci Rep. 2017 Mar 20;7:44791. doi: 10.1038/srep44791.
  • Day C., Shepherd J.D. Arc: building a bridge from viruses to memory. Biochem J. 2015 Jul 1;469(1):e1-3. doi: 10.1042/BJ20150487
  • Gee J.M., Smith N.A., Fernandez F.R., Economo M.N., Brunert D., Rothermel M., Morris S.C., Talbot A., Palumbos S., Ichida J., Shepherd J.D., West P.J., Wachowiak M., Capecchi M.R., Wilcox K.S., White J.A., Tvrdik P. Imaging Activity in Neurons and Glia with a Polr2a-based and Cre-dependent GCaMP5G-IRES-tdTomato Reporter Mouse. Neuron 2014 Sep 3;83(5):1058-72.
  • Uzunova G., Hollander E., Shepherd J.D. The Role of Ionotropic Glutamate Receptors in Childhood Neurodevelopmental Disorders: Autism Spectrum Disorders and Fragile X Syndrome. Current Neuropharmacology, 2014 Jan;12(1):71-98.
  • Shepherd J.D. Memory, plasticity and sleep – A role for calcium permeable AMPA receptors?  Front Mol Neurosci. 2012;5:49.
  • Wu J., Petralia R.S., Kurushima H., Patel H., Jung M., Volk L., Chowdhury S., Shepherd J.D.,  Dehoff M., Li Y., Kuhl D., Huganir R.L., Price D.L., Scannevin R., Troncoso J.C., Wong P.C.,  Worley P.F. Arc/Arg3.1 Regulates an Endosomal Pathway Essential for Activity-Dependent β- Amyloid Generation. Cell. 2011 Oct 27;147(3):615-628.
  • Shepherd J.D and Bear M.F. New views of Arc, a master regulator of synaptic plasticity. Nature  Neuroscience. 2011 March; 14(3): 279–284.
  • Smith-Hicks C, Xiao B, Deng R, Ji Y, Zhao X, Shepherd J.D, Posern G, Kuhl D, Huganir R.L,  Ginty D.D, Worley P.F, Linden D.J. SRF binding to SRE 6.9 in the arc promoter Is essential for the late phase of LTD in cultured cerebellar purkinje cells. Nature Neuroscience 2010 Sep;13(9):1082-9.
  • McCurry C*., Shepherd J.D.*, Tropea D., Wang K., Bear M.F., Sur M. Loss of Arc renders the  visual cortex impervious to the effects of sensory experience or deprivation. Nature Neuroscience. 2010 Apr;13(4):450-7.
  • Park S., Park J.M., Kim S., Kim J.A., Shepherd J.D., Smith-Hicks C.L., Chowdhury S., Kaufmann W., Kuhl D., Ryazanov A.G., Huganir R.L., Linden D.J., Worley P.F. (2008). Eukaryotic elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc essential for mGluR-LTD. Neuron 2008 Jul 10;59(1):70-83.
  • Shepherd J.D, Huganir R.L The cell biology of synaptic plasticity: AMPA receptor trafficking. Annual Review of Cell and Developmental Biology. 2007 Nov Vol. 23: 613-643.
  • Shepherd J.D.*, Rumbaugh G.*, Wu J. Chowdhury S., Plath N., Kuhl D., HuganirR.L., Worley P.F. Arc/Arg3.1 Mediates synaptic scaling of AMPA receptors. Neuron. 2006 Nov 9;52(3):475-84.
  • Chowdhury S.* Shepherd J.D.*, Ojuno H., Lyford G.,Petralia R., Plath N., Kuhl D., HuganirR.L., WorleyP.F. Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron. 2006 Nov 9;52(3):445-59.
  • Oddo S, Caccamo A*, Shepherd J.D*, Murphy M.P, Golde T.E, Kayed R, Metherate R, Mattson M.P, Akbari Y, LaFerla F.M. Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron. 2003 Jul 31;39(3):409-21.

*Equal contribution

Invited Lectures
  •  CSHL Retrovirus Meeting, 2018.
  • Keystone Symposium: Exosomes/Microvesicles: Heterogeneity, Biogenesis, Function and Therapeutic Developments, 2018.
  • EMBO Meeting: Dendritic anatomy, molecules and function. Heraklion, Greece, 2018.
  • Department of Molecular Pharmacology and Therapeutics student invited seminar, Loyola University Chicago, 2018.
  • Neuroscience program student invited seminar, University of Wyoming, 2018.
  • Janelia Research Campus, Systems Neuroscience Seminar Series, 2018.
  • CPIN Emerging Leaders in Neuroscience Lecture, University of Toronto, 2018.
  • Brandeis University, Department of Biology, 2017.
  • Panel Chair, Winter Conference on Brain Research, Big Sky Resort, 2017.
  • University of Massachusetts Medical School, Department of Neurobiology, 2017.
  • Gordon Research Conference, Excitatory Synapses and Brain Function – Switzerland, 2017.
  • The Angleman Syndrome Foundation Annual Conference – Phoenix, 2017.
  • Center for the Neurobiology of Learning and Memory, University of California – Irvine, 2016.
  • National Academy of Sciences – Kavli Frontiers in Science Symposium, Newport CA, 2016.
  • Stanford University, Department of Molecular and Cellular Physiology, 2016.
  •  Gordon Research Conference on Synaptic Transmission, August 2016.
  • University of Colorado Medical School, Department of Pharmacology Seminar Series. February, 2016.
  •  Keynote Speaker: The Cellular and Molecular Medicine Graduate Program Retreat, Johns Hopkins University. October, 2015.
  • The Long and Winding Road: Neuronal Trafficking in Physiology and Disease. HHMI conference, Janelia Farms. May, 2015.
  • Panel Chair, Winter Conference on Brain Research, Big Sky Resort. January 2015.
  •  Hospital for Sick Children, Neurosciences & Mental Health program.Toronto. July 2014.
  • Keynote Speaker: University of Auckland, Centre for Brain Research Retreat. Oct 2013.
  •  University of Arizona, Evelyn McKnight Institute. Tucson, June 2013.
  • Spring Hippocampus Meeting. Taormina, Italy. June 2013.
  • University of Texas Southwestern Medical School, Department of Psychiatry. February 2012.
  • University of Utah, Department of Neurobiology and Anatomy. Utah, January 2012.
  • Rutgers University, Deparment of Cell Biology and Neuroscience. NJ, January 2012.
  • Baylor College of Medicine, Department of Neuroscience/NRI. Houston, November 2011.
  • Mount Sinai School of Medicine, Department of Neuroscience. NY, October 2011.
  • Florey Neuroscience Institute, Melbourne University. Melbourne, September 2011.
  • ISN Young Lectureship, ISN-ESN Biennial Meeting. Athens, Greece. August 2011.
  • University of Michigan, Molecular and Behavioral Neuroscience Institute. March 2011.
  • Tufts University School of Medicine, Department of Neuroscience. February 2011.
  • Northwestern University, Department of Physiology. October 2010.
  • Angelman Foundation Symposium, Chapel Hill. April, 2010.
  • University of Auckland, School of Medicine seminar series. December, 2009.
  • The Synaptic Basis of Disease Conference, Geneva. July 2008.
  • Albert Einstein College of Medicine, Department of Neuroscience Seminar Series. April 2007.
  • University of Maryland, Program in Cognitive Sciences Seminar Series. February 2007.
  • Winter Conference in Neural Plasticity, Tahiti. February 2007.
  • University of Cambridge, MRC Laboratory of Molecular Biology, November 2006.
  • The 16th Neuropharmacology Conference, Atlanta. USA . October 2006.
Teaching Experience
  • NEUSC 6040. Molecular and Cellular Neuroscience. Lecturer. University of Utah, 2013 –
  • NEUSC 6040: Course Director. 2015 –
  • Course Instructor, Course 7.347 Advanced Seminar in the Cell Biology of the Synapse. MIT, 2009.
  • Teaching Assistant: MCB 80 (Sanes and Lichtman) – The Neurobiology of Behavior, Harvard University, 2009.
  • Teaching Assistant: Neuroscience for medical students (Lab and discussion groups), Johns Hopkins School of Medicine, 2004-06.
Professional Activities
  • Associate Editor: Frontiers in Molecular Neuroscience
  • Review Editor: Frontiers in Synaptic Neuroscience
  • Journal Reviewer: Journal of Neurophysiology, Journal of Physiology, Neurobiology of Learning and Memory, Journal of Neuroscience, Frontiers in Neuroscience, Science Signaling, Translational Psychiatry, Cellular and Molecular Life Sciences, Molecular Autism, Neural Plasticity, Journal of Visualized Experiments (JoVE), Journal of Clinical Investigation, Trends in Neuroscience, Neuron, eLife, Nature Neuroscience, Cell Reports, Nature Communications.
  • Grant reviewer: Fragile X Research Foundation, Angelman Syndrome Foundation, Welcome Trust Foundation, The Netherlands Organisation for Health Research and Development, The Florida Department of Public Health – Florida Alzheimer’s Disease Research Program.
  • Graduate admissions committee: University of Utah Neuroscience Graduate Program 2013 – 2016
  • Director – Synapse Interesting Group, University of Utah
  • Faculty search committee, Department of Neurobiology and Anatomy – University of Utah 2013/14.
  • Co-Chair, Faculty search committee, Department of Neurobiology and Anatomy – University of Utah 2018.
  • Organizer, Department of Neurobiology and Anatomy Seminar Series, 2016 –
  • Member of the Society for Neuroscience 2003 –
  • Vice-President of MIT Rugby Football Club 2008 – 2012.
  • USA Rugby certified referee
  • REDDIT Science AMA Session, 2014.
  • TEDxSaltLakeCity – Steering Committee Member. 2014 – 2017.
  • Member of the American Society of Cell Biology 2018 –