Shepherd, Jason Dennis, PhD

Research Interests

  • Neurodegenerative Diseases
  • Neurosciences
  • Neurodevelopmental Disorders
  • Synaptic Transmission
  • Synaptic Membranes
  • Synaptic Plasticity
  • Learning and Memory
  • Receptor Trafficking
  • Immediate-Early Proteins
  • Endocytosis
  • Autism Spectrum Disorders
  • Angelman Syndrome
  • Fragile X Syndrome
  • Rett Syndrome
  • Alzheimer's Disease

Labs

Lab Website

Languages

  • English

Academic Information

  • Departments: Biochemistry - Adjunct Assistant Professor, Neurobiology & Anatomy - Assistant Professor, Ophthalmology/Visual Sciences - Adjunct Assistant Professor

Academic Office Information

  • 801-585-6214
  • James LeVoy Sorenson Molecular Biotechnology Building
    Neurobiology and Anatomy
    36 South Wasatch Drive, Room: 4539
    Salt Lake City, UT 84112

Email: u0859692@utah.edu

Academic Bio

Brains 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.

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

Education History

Type School Degree
Postdoctoral Fellowship The Picower Institute for Learning and Memory, Massachusetts Institute of Technology
K99 award
Postdoctoral Fellow
Postdoctoral Fellowship Howard Hughes Medical Institute
The Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Postdoctoral Fellow
Doctoral Training The Johns Hopkins School of Medicine
Medicine
Ph.D.
Graduate Training University of California, Irvine
Neurobiology and Behavior Graduate Program as an Exchange Abroad Scholar (counted towards undergraduate degree)
Undergraduate University of Otago
First Class Honours in Neuroscience
B.S.
Other Training Intercultural Exchange in Switzerland, Kantonschule Trogen
American Field Scholar (AFS)

Global Impact

Education History

Type School Degree Country
Undergraduate University of Otago
First Class Honours in Neuroscience
B.S. New Zealand
Other Training Intercultural Exchange in Switzerland, Kantonschule Trogen
American Field Scholar (AFS)
Switzerland

Awards & Honors

Description Country
Peter and Patricia Gruber International Research Award in Neuroscience Global
International Society for Neurochemistry Young Investigator Award Global

Selected Publications

Journal Article

  1. Shepherd JD (2018 Oct). Deconstructing the synapse. Nat Neurosci, 21(10), 1294-1295.
  2. Eavri R, Shepherd J, Welsh CA, Flanders GH, Bear MF, Nedivi E (2018 Sep 26). Interneuron Simplification and Loss of Structural Plasticity As Markers of Aging-Related Functional Decline. J Neurosci, 38(39), 8421-8432.
  3. Shepherd, JD (). Deconstructing the Synapse. Nat Neurosci, 21(10), 1294-1295.
  4. Wall MJ, Collins DR, Chery SL, Allen ZD, Pastuzyn ED, George AJ, Nikolova VD, Moy SS, Philpot BD, Shepherd JD, Muller J, Ehlers MD, Mabb AM, Correa SAL (2018 Jun 27). The Temporal Dynamics of Arc Expression Regulate Cognitive Flexibility. Neuron, 98(6), 1124-1132.e7.
  5. Pastuzyn ED, Day CE, Kearns RB, Kyrke-Smith M, Taibi AV, McCormick J, Yoder N, Belnap DM, Erlendsson S, Morado DR, Briggs JAG, Feschotte C, Shepherd JD (2018 Jan 11). The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer. Cell, 172(1-2), 275-288.e18.
  6. Jenks KR, Kim T, Pastuzyn ED, Okuno H, Taibi AV, Bito H, Bear MF, Shepherd JD (2017 Aug 22). Arc restores juvenile plasticity in adult mouse visual cortex. Proc Natl Acad Sci U S A, 114(34), 9182-9187.
  7. Pastuzyn ED, Shepherd JD (2017). Activity-Dependent Arc Expression and Homeostatic Synaptic Plasticity Are Altered in Neurons from a Mouse Model of Angelman Syndrome. Front Mol Neurosci, 10, 234.
  8. Day C, Shepherd JD (2015 Jul 1). Arc: building a bridge from viruses to memory. Biochem J, 469(1), e1-3.
  9. Gee JM, Smith NA, Fernandez FR, Economo MN, Brunert D, Rothermel M, Morris SC, Talbot A, Palumbos S, Ichida JM, Shepherd JD, West PJ, Wachowiak M, Capecchi MR, Wilcox KS, White JA, Tvrdik P (2014 Sep 3). Imaging activity in neurons and glia with a Polr2a-based and cre-dependent GCaMP5G-IRES-tdTomato reporter mouse. Neuron, 83(5), 1058-72.
  10. Shepherd JD (2012). Memory, plasticity and sleep - A role for calcium permeable AMPA receptors? Front Mol Neurosci, 5, 49.
  11. Wu J, Petralia RS, Kurushima H, Patel H, Jung MY, Volk L, Chowdhury S, Shepherd JD, Dehoff M, Li Y, Kuhl D, Huganir RL, Price DL, Scannevin R, Troncoso JC, Wong PC, Worley PF (2011 Oct 28). Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent beta-amyloid generation. Cell, 147(3), 615-28.
  12. McCurry CL, Shepherd JD, Tropea D, Wang KH, Bear MF, Sur M (2010 Apr). Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation. Nat Neurosci, 13(4), 450-7.
  13. Smith-Hicks C, Xiao B, Deng R, Ji Y, Zhao X, Shepherd JD, Posern G, Kuhl D, Huganir RL, Ginty DD, Worley PF, Linden DJ (2010 Sep). SRF binding to SRE 6.9 in the Arc promoter is essential for LTD in cultured Purkinje cells. Nat Neurosci, 13(9), 1082-9.
  14. Park S, Park JM, Kim S, Kim JA, Shepherd JD, Smith-Hicks CL, Chowdhury S, Kaufmann W, Kuhl D, Ryazanov AG, Huganir RL, Linden DJ, Worley PF (2008 Jul 10). Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3.1 essential for mGluR-LTD. Neuron, 59(1), 70-83.
  15. Chowdhury S, Shepherd JD, Okuno H, Lyford G, Petralia RS, Plath N, Kuhl D, Huganir RL, Worley PF (2006 Nov 9). Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron, 52(3), 445-59.
  16. Shepherd JD, Rumbaugh G, Wu J, Chowdhury S, Plath N, Kuhl D, Huganir RL, Worley PF (2006 Nov 9). Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA receptors. Neuron, 52(3), 475-84.
  17. Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM (2003 Jul 31). Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron, 39(3), 409-21.
  18. Soto R, D Brown G, Worne C, Pastuzyn ED, Bell R, Petersen C, Buhrke K, Fujinami R, OConnell RM, Stephens WZ, Shepherd JD, Lane TE and Round JL (). Early life exposure to gut bacterial products prime microglia to protect from viral-induced neurologic disease. Nat Immunol.

Review

  1. Shepherd JD (2018 May). Arc - An endogenous neuronal retrovirus? [Review]. Semin Cell Dev Biol, 77, 73-78.
  2. Shepherd JD, Bear MF (2011 Mar). New views of Arc, a master regulator of synaptic plasticity. [Review]. Nat Neurosci, 14(3), 279-84.
  3. Shepherd JD, Huganir RL (2007). The cell biology of synaptic plasticity: AMPA receptor trafficking. [Review]. Annu Rev cell Dev Biol, 23, 613-43.