Andrew J. Shepherd, Ph.D.


Instructor

Department of Anesthesiology

Washington University Pain Center

Washington University School of Medicine in St. Louis

5502 CSRB

660 S. Euclid Avenue, St. Louis, MO 63110

Voice - (314) 362-8244

a.shepherd[at]wustl.edu



I received a Ph.D. in Life Sciences from the University of Manchester (Manchester, UK) in 2006 and joined this group as a postdoctoral research scholar in 2008, when the laboratory was in the Department of Pharmacology at The University of Iowa Carver College of Medicine.  During my graduate studies I received training in neuroimmunology, and during my postdoctoral training I received training in  cell/molecular biology, functional ion imaging, neuroanatomy, mouse models of human diseases, and diverse behavioral assessment of pain, activity and motor functions in rodents.  I have been handling multiple projects in the laboratory, but focussing mainly on three projects:

 

1. Developing and validating mouse models of bone-metastasized prostate cancer and the development of chronic pain associated with such bone metastasis.  Furthermore, I am investigating functional and anatomical modifications in sensory TRP channels by a variety of osteolytic & vasoactive peptides, chemokines and cytokines that are enriched in metastatic bone tumor microenvironment, as an underlying mechanism for chronic pain associated with bone-metastasized prostate cancers.


2. Investigating specific peripheral neuro-immune interactions that lead to sensory nerve excitation and development of chronic pain associated with obesity.


3. Investigating neuronal survival death dynamics in mammalian brain neurons via specific modifications in Kv channels and regulation of neuronal excitability in multiple neurodegenerative conditions, such as stroke-reperfusion injury and exposure to several HIV-1 regulatory/surface proteins.


To address these important and exciting scientific questions I am utilizing membrane protein biochemistry, molecular/cell biology, functional Ca2+ and K+ imaging, immunohisto/cytochemistry, in vitro & in vivo pharmacology,  primary cultures of rodent neurons and their co-culture with human cancer cells, generation of xenografts of human cancers resulting in bone metastasis in scid mice, non-invasive monitoring of tumor growth and oxidative/nitrosative stress by whole-animal bioluminescence & radiographic imaging, and most importantly, diverse pain-, motor- and activity-related behavioral assessments in rodents.  In addition, I utilize mouse genetics approaches in these projects.


Apart from my research I enjoy still photography of nature, and love baking.



Publications:


  1. 1.Shepherd A.J.*, and Mohapatra D.P.* (2018). Attenuation of un-evoked mechanical and cold pain hypersensitivity associated with experimental neuropathy in mice by Angiotensin II type-2 receptor antagonism.  Anesthesia & Analgesia. In Press.  *Corresponding author


  1. 2.Shepherd A.J.*, Mickle A.D., Karlsson P., Golden J.P., Mack M.R., Halabi C.M., de Kloet A.D., Samineni V.K., Kim B.S., Krause E.G., Gereau IVth R.W., and Mohapatra D.P.* (2018).  Macrophage angiotensin II type 2 receptor triggers neuropathic pain.  Proceedings of the National Academy of Sciences USA Aug 6 pii: 201721815. doi: 10.1073/pnas.1721815115.  *Corresponding author


  1. 3.Shepherd A.J., Copits B., Mickle A.D., Karlsson P., Kadunganattil S., Haroutounian S., Tadinada S.M., de Kloet A.D., Valtcheva M.V., McIlvried L.A., Sheahan T.D., Jain S., Ray P., Usachev Y.M., Dussor G., Krause E.G., Price T.J., Gereau IVth R.W., and Mohapatra D.P. (2018).  Angiotensin II triggers peripheral macrophage-to-sensory neuron redox crosstalk to elicit pain.  Journal of Neuroscience Vol. 38(32):7032-7057.


  1. 4.Shepherd A.J., Cloud M.E., Cao Y.-Q., and Mohapatra D.P. (2018).  Deficits in burrowing behaviors are associated with mouse models of neuropathic but not inflammatory pain or migraine.  Frontiers in Behavioral Neuroscience  Vol. 12: 124. doi: 10.3389/fnbeh.2018.00124.


  1. 5.Shepherd A.J., Mickle, A.D., McIlvried L.A., Gereau IVth R.W., and Mohapatra D.P. (2018).  Parathyroid hormone-related peptide activates and modulates TRPV1 channel in human DRG neurons.  European Journal of Pain  [Epub ahead of print]. doi: 10.1002/ejp.1251, 2018.


  1. 6.Shepherd A.J.*, Mickle, A.D.*, Kadunganattil S.*, Hu H., and Mohapatra D.P. (2018).  Parathyroid hormone-related peptide elicits peripheral TRPV1-dependent mechanical hypersensitivity.  Frontiers in Cellular Neuroscience  Vol. 12 (article-38): 1-14.  *Equal contribution.


  1. 7.Shepherd A.J.* and Mohapatra D.P.* (2018).  Pharmacological validation of voluntary gait and mechanical sensitivity assays associated with inflammatory and neuropathic pain in mice.  Neuropharmacology  Vol. 130: 18-29. *Corresponding author


  1. 8.Sheahan T.D., Siuda E.R., Bruchas M.R., Shepherd A.J., Mohapatra D.P., Gereau IVth R.W., and Golden, J.P. (2017).  Inflammation and injury minimally affect mouse voluntary behaviors proposed as indicators of pain. Neurobiology of Pain Vol. 2:1-12.


  1. 9.Meacham K., Shepherd A.J., Mohapatra D.P., and Haroutounian S. (2017).  Neuropathic pain: central vs. peripheral mechanisms. Current Pain and Headache Reports Vol. 21(6):28.


  1. 10.Mickle A.D.*, Shepherd A.J.*, and Mohapatra D.P. (2016).  Nociceptive TRP channels: sensory detectors and transducers in multiple pain pathologies. Pharmaceuticals Vol. 9(4): pii:E72.  *Equal contribution.


  1. 11.Shutov L., Warwick C.A., Shi X., Gnanasekaran A., Shepherd A.J., Mohapatra D.P., Woodruff T.M., Clark, D.J., and Usachev Y.M. (2016).  The complement system component C5a produces thermal hyperalgesia via macrophage-to-nociceptor signaling that requires NGF and TRPV1.  Journal of Neuroscience Vol. 38(18):4993-5002.


  1. 12.Gupte R.P., Kadunganattil S., Shepherd A.J., Merrill R.A., Planer W., Bruchas M.R., Strack S., and Mohapatra D.P. (2016).  Convergent Phosphomodulation of the major neuronal dendritic potassium channel Kv4.2 by pituitary adenylate cyclase-activating polypeptide.  Neuropharmacology  Vol. 101:291-308.


  1. 13.Mickle, A.D., Shepherd A.J., Loo L., and Mohapatra D.P. (2015). Induction of thermal and mechanical hypersensitivity by parathyroid hormone-related peptide (PTHrP) through upregulation of TRPV1 function and trafficking.  Pain Vol. 156(9): 1620-1636.


  2. 14.Mickle, A.D.*, Shepherd A.J.*, and Mohapatra D.P. (2015). Sensory TRP channels: The key transducers of nociception and pain. In “Molecular and Cell Biology of Pain”, Progress in Molecular Biology and Translational Science.  Vol. 131: 73-118*Equal contribution 1st Author.


  1. 15.Kim K.Y., Scholl E.S., Liu X., Shepherd A.J., Haeseleer, F., and Lee A. (2014). Localization and expression of CaBP1/caldendrin in the mouse brain.  Neuroscience.  Vol. 268: 33-47.

  2. 16.Shepherd A.J., Loo L., and Mohapatra D.P. (2013). Chemokine co-receptor CCR5/CXCR4-dependent modulation of Kv2.1 channel confers acute neuroprotection to HIV-1 glycoprotein gp120.  PLoS One.  Vol. 8(9): e76698.


  1. 17.Sowers L.P., Loo L., Wu Y., Campbell E., Ulrich J.D., Wu S., Paemka L., Wassink T., Meyer K., Bing X., El-Shanti H., Usachev Y.M., Ueno N., Manak J.R., Shepherd A.J., Ferguson P.J., Darbro B.W., Richerson G.B., Mohapatra D.P., Wemmie J.A., and Bassuk A.G. (2013). Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction.  Molecular Psychiatry.  Vol. 18(10): 1077-1089.


  1. 18.Hall D.D., Dai S., Tseng P.Y., Malik Z., Nguyen M., Matt L., Schnizler K., Shepherd A.J., Mohapatra D.P., Tsuruta F., Dolmetsch R.E., Christel C.J., Lee A., Burette A., Weinberg R.J., Hell J.W. (2013). Competition between α-actinin and Ca²⁺-calmodulin controls surface retention of the L-type Ca²⁺ channel Cav1.2.  Neuron.  Vol. 78(3): 483-497.


  1. 19.Shepherd A.J., Loo L., Gupte R.P., Mickle A.D., and Mohapatra D.P. (2012). Distinct modifications in Kv2.1 channel via chemokine receptor CXCR4 regulate neuronal survival-death dynamics.  Journal of Neuroscience.  Vol. 32(49): 17725-17739.

  2. 20.Loo L., Shepherd A.J., Mickle A.D., Lorca R.A., Shutov L., Usachev Y.M., and Mohapatra D.P. (2012). The C-type natriuretic peptide induces thermal hyperalgesia through a non-canonical Gβγ-dependent modulation of TRPV1 channel.  Journal of Neuroscience.  Vol. 32(35): 11942-11955.


  1. 21.Shepherd A.J., and Mohapatra D.P. (2012). Tissue Preparation and immunostaining of mouse sensory nerve fibers innervating skin and limb bones.   Journal of Visualized Experiments.  Vol. 59, e3485.


  1. 22.Maity B., Stewart A., Yang J., Loo L., Sheff D., Shepherd A.J., Mohapatra D.P., and Fisher R.A. (2012). Regulator of G protein Signaling 6 (RGS6) ensures coordination of motor movement by modulating GABAB receptor signaling.  Journal of Biological Chemistry.  Vol. 287(7): 4972-4981.


  1. 23.Bocksteins E.*, Shepherd A.J.*, Mohapatra D.P., and Snyders D.J. (2012). Immunostaining of cell lines and neurons- key concepts and potential pitfalls. In “Immunocytochemistry”, Hesam Dehghani Ed., ISBN 978-953-308-18-9.  *Equal contribution 1st Author.


  1. 24.Yang J., Huang J., Maity B., Gao Z., Lorca R.A., Gudmundsson H., Li J., Stewart A., Swaminathan P.D., Ibeawuchi S.-R., Shepherd A.J., Chen C.-K., Kutschke W., Mohler P., Mohapatra D.P., Anderson M.E., and Fisher R.A. (2010). RGS6, a modulator of parasympathetic activation in heart.  Circulation Research. Vol. 107(11): 1345-1349.


  1. 25.Cains S., Shepherd A., Nabiuni M., Owen-Lynch P.J., and Miyan J. (2009). Addressing a folate imbalance in fetal cerebrospinal fliud can decrease the incidence of congenital hydrocephalus.  Journal of Neuropathology & Experimental Neurology. Vol. 68(4): 404-416.


  1. 26.Shepherd A.J., Downing J.E., and Miyan J.A. (2005). Without nerves, immunology remains incomplete - in vivo veritas.  Immunology.  Vol. 116(2): 145.


  1. 27.Shepherd A.J., Beresford L.J., Bell E.B., and Miyan J.A. (2005). Mobilisation of specific T cells from lymph nodes in contact sensitivity requires substance P.  Journal of Neuroimmunology.  Vol. 164(1-2): 115.