Jason Shepherd

Jason Shepherd

Dr. Jason Shepherd. Photo by Azeddine Tahiri

Jason Shepherd, Ph.D.

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

Contact Information

Maxwell Wintrobe Research Bldg, Office: 531A
University of Utah School of Medicine
Salt Lake City, UT 84132

Office:   (801) 587-7854
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. In particular, the enduring nature of memory remains a mystery, despite intensive study. How does information storage remain stabile for years, despite constant protein modification and turnover? Moreover, disorders of memory and cognition affect millions of people and are generally intractable to treatment. A major challenge in neuroscience is to understand how neuronal networks are modified through experience and how proteins/genes contribute to circuit modification. However, answering these fundamental questions requires many levels of analysis: from molecular interactions to complex cognition. Clearly, a multidisciplinary and collaborative approach is required. The fascinating and challenging aspect of neuroscience is to bridge these gaps of analysis and be able to synthesize work coming from disparate areas of research.

My lab is interested in elucidating the fundamental cellular and molecular processes that underlie memory formation. In particular we are interested in the elucidation of the protein machinery at the synapse that governs long-term storage of information, and how basic cell biological processes have been elaborated in neurons for the purpose of modulating synaptic transmission. In addition, we are interested in how these processes go awry in neurological diseases.

It has been known since the 1960s that new protein synthesis is required for stabile memory, yet it remains unclear how and why. Moreover, neural circuits are refined during development through activity-dependent gene and protein expression. Similar macromolecular synthesis is essential for long-term forms of synaptic plasticity such as long-term potentiation (LTP) and depression (LTD). Efforts to identify genes that underlie

transcription-dependent plasticity have revealed a set of immediate early genes (IEGs) that target to excitatory synapses. Many of these IEGs such as Arc, Narp, Homer and PKM zeta have critical roles in synaptic function and plasticity, and have also been implicated in various neurological disorders. Among brain IEGs identified to date, Arc is the most tightly coupled to behavioral encoding of information in neuronal circuits. Indeed, Arc’s transcription has been used in many labs as a tool to mark neural circuits involved in behavioral paradigms across many species. Mice that lack Arc are profoundly deficient in long-term memory consolidation and in both synaptic and experience-dependent plasticity. Arc expression is exquisitely fined tuned; transcription is rapid and activity-dependent, mRNA is transported to dendrites and protein is locally translated in response to various signaling pathways. Arc protein regulates the AMPA type glutamate receptor at excitatory synapses.

Why is Arc so tightly regulated? How does Arc render memories stabile? What is Arc’s precise synaptic function? The uniqueness of Arc is that it allows one to study mechanisms of neural circuit development and refinement at both the synaptic and circuit level, providing insight in how to bridge molecules and behavior.

We primarily use the mouse visual cortex to investigate the mechanisms that underlie experience-dependent plasticity because of the ease of manipulating visual experience and because of its well-defined circuitry. The lab utilizes coordinated biochemical, cell biological, electrophysiological and imaging studies in vitro and in vivo, including state of the art techniques such as in vivo two-photon microscopy and chronic electrophysiological recordings in live animals.

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 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
  • 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
  • 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
  • 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
  • Ad hoc reviewer: Journal of Neurophysiology
  • Ad hoc reviewer: Journal of Physiology
  • Ad hoc reviewer: Neurobiology of Learning and Memory
  • Grant reviewer: Fragile X Research Foundation
  • Grant reviewer: Welcome Trust Foundation
  • Grant reviewer: The Netherlands Organisation for Health Research and Development
  • Member of the Society for Neuroscience
  • Vice-President of MIT Rugby Football Club 2008 – present.