Pharmacology

Durga P. Mohapatra, PhD

Portrait

Associate Professor of Pharmacology
Associate Professor of Anesthesia

Contact Information

Primary Office: 2-430 Bowen Science Building
Iowa City, IA 52242
Primary Office Phone: 319-335-6944

Lab: 2-440 Bowen Science Building
Iowa City, IA 52242
Phone: 319-335-6922

Email: dp-mohapatra@uiowa.edu

Education

BS, Zoology (Honors), Utkal University, Bhubaneswar (India)
MSc, Biochemistry, National Diary Research Institute, Karnal (India)
PhD, Human Biology (Neuroscience), Faculty of Medicine, University of Erlangen-Nuremberg (Germany)

Junior Research Fellow, Postgraduate Institute of Medical Education and Research, Chandigarh (India)
Junior & Senior Research Fellow, All India Institute of Medical Sciences, New Delhi (India)
Postdoctoral Research Fellow, Department of Pharmacology, School of Medicine, and Department of Neurobiology, Physiology and Behavior, University of California at Davis, CA

Education/Training Program Affiliations

Biosciences Graduate Program
Interdisciplinary Graduate Program in Neuroscience
Medical Scientist Training Program

Research Summary

Mechanisms of peripheral pain transduction associated with bone-metastasized prostate/breast cancers, as well as in chronic inflammation

We are investigating distinct modifications in TRP and Nav channels in mammalian sensory neurons by a variety of growth factors, cytokines and peptides released at elevated levels from bone-metastasized prostate/breast cancer cells & the surrounding tumor microenvironment. Sustained modifications in the activity and expression of these channels could lead to constitutive sensitization of neuronal firing in sensory afferents innervating bones, ultimately resulting in chronic pain associated with these metastatic bone cancers. We utilize in vitro mouse sensory neuron cultures, co-cultures of neurons with human cancer cells, immunohistochemistry, biochemistry, cell/molecular biology, Ca2+ imaging, electrophysiology, and in vitro pharmacology to delineate the cellular/molecular mechanistic bases underlying nociceptor sensitization associate with cancer pain. In order to verify these mechanistic bases of chronic pain sensitization in vivo we utilize mouse xenograft models of human prostate/breast cancer bone metastasis for the assessment of a battery of bone-related un-evoked pain behavioral responses. Finally, we employ in vivo pharmacology, as well as use xenografts of human cancer cells in specific gene knockout mice, in order to verify the utility of specific TRP and Nav channels as metastatic bone cancer pain therapeutic targets. Our long-term goal is to target such modifications in TRP and Nav channels for the development of highly specific and efficacious analgesics for the management of cancer pain.

We are also investigating the role of specific inflammatory mediators, such as natriuretic peptides, in the modulation of TRP and Nav channels in mammalian sensory neurons and sensitization of their firing properties, which presumably underlie a peripheral transduction mechanism for inflammatory pain such as arthritis. We utilize similar experimental approach as mentioned above, additionally with the use of mouse models of osteoarthritis to address these questions. Again, our long-term goal is to target specific TRP and Nav channels, and the specific modulations there in for the development of highly specific and efficacious analgesics for inflammatory pain associated with arthritis. For both metastatic bone cancer pain and arthritis pain projects, we envision on developing strategies for specific bone-targeted delivery of combinations of anti-tumor & analgesic, and anti-inflammatory & analgesic drugs for the efficacious management of tumor/bone/joint inflammatory pathologies and the debilitating pain associated with those.

Regulation of neuronal excitability and survival-death dynamics via modulation of Kv channels in mammalian brain neurons during brain tumor induced hyperexcitability, HIV-associated neurodegeneration, and ischemic stroke

We are investigating distinct short- and long-term changes in the expression, localization and functions of Kv channels in mammalian brain neurons by factors/mediators released during ischemic stroke-reperfusion injury, as well as from brain tumor cells, acting through specific GPCRs and growth factor receptors. A number of such modifications in Kv channel localization and function provide cellular plasticity by altering the intrinsic membrane excitability, thereby providing the neurons with a mechanism for neuroprotection. However, distinct long-term modifications in Kv channel expression/ localization/function could also induce neuronal death or neurodegeneration. We are specifically interested in studying the coordinated interplay between distinct Kv channel modulations and membrane excitability in the neuronal soma and dendrites that regulate neuronal survival-death dynamics in response to seizures, ischemic stroke, brain tumor growth, and HIV-associated neurodegeneration & neurocognitive disorders (HAND). We utilize in vitro rodent hippocampal and cortical neuron cultures, co-cultures of neurons with human cancer cells, immunohistochemistry, biochemistry, cell/molecular biology, functional single ion imaging, electrophysiology, and in vitro pharmacology to delineate the cellular/molecular mechanistic bases underlying Kv channel modulations and regulation of membrane excitability upon these neuropathological conditions. In order to verify these mechanistic bases in vivo we plan to utilize mouse middle cerebral artery occlusion model of ischemic stroke-reperfusion injury, rodent xenograft models of human glioma/glioblastoma, as well as the HIV-1 gp120 transgenic mouse model of HAND. Our long-term goal is to target such modifications in specific Kv channels as a convergent point or switch for neuroprotective and neuronal death processes under various hyperexcitable and neurodegenerative pathologies, based on which future pharmacotherapeutic strategies can be developed.

Center, Program and Institute Affiliations

Pain Research Program

All Publications

Shepherd A, Loo L, Mohapatra D.  Chemokine co-receptor CCR5/CXCR4-dependent modulation of Kv2.1 channel confers acute neuroprotection to HIV-1 glycoprotein gp120 exposure.  PLoS ONE.  2013 August. In Press.

Sowers L, Loo L, Wu Y, Campbell E, Ulrich J, Wu S, Paemka L, Wassink T, Meyer K, Bing X, El-Shanti H, Usachev Y, Ueno N, Manak R, Shepherd A, Ferguson P, Richarson G, Mohapatra D, Wemmie J, Bassuk A.  PRICKLE2 defects link the non-canonical Wnt pathway to autism.  Molecular Psychiatry.  2013 May 28. [Epub ahead of print]:doi: 10.1038/mp.2013.71.
[Link]

Hall D, Dai S, Tsuruta F, Malik Z, Schnizler K, Shepherd A, Mohapatra D, Lee A, Burette A, Weinberg R, Dolmetsch R, Hell J.  Competition between α-actinin and Ca2+-calmodulin controls retention of the L-type Ca2+ channel Cav1.2.  Neuron.  2013 May 8. 78(3):483-497.
[Link]

Shepherd A, Loo L, Mohapatra D.  Attenuation of HIV-1 glycoprotein gp120-induced neuronal cell death by the anti-Alzheimerʼs drug Donepezil via selective blockade of the voltage-gated K+ channel Kv2.1.  2013. 

Loo L, Shepherd A, Usachev Y, Mohapatra D.  C-type natriuretic peptide and PKC-mediated potentiation of TRPV1 activity, nociceptor sensitization and thermal hyperalgesia operate independently of AKAP150.  2013. 

Tiwari A, Loo L, Shepherd A, Mohapatra D.  Impaired cell surface trafficking and dominant negative effects of mutations in the pore helix of Kv channels.  2013. 

Shepherd A, Gupte R, Mohapatra D.  Neuro-immune interactions in neurodegenerative disorders: the critical role of neuronal voltage-gated K+ channels.  2013. 

Shepherd A, Tiwari A, Loo L, Strack S, Mohapatra D.  Sensory afferent sprouting and enhanced TRPV1 expression/function govern C-type natriuretic peptide-induced peripheral mechanical hypersensitivity.  2013. 

Tiwari A, Shepherd A, Mohapatra D.  Toxins acting on K+ channels and neurotoxicity.  2013. 

McNeill M, Bonde G, Lorca R, Chen Y, MacArthur H, Mohapatra D, Panula P, Cornell R.  Zebrafish TRPM7 mutant embryos are hypomotile and sensitized to MPP-induced loss of dopamine neurons.  PNAS.  2013. 

Ulrich J, Kim M, Houlihan P, Shutov L, Mohapatra D, Strack S, Usachev Y.  Distinct activation properties of the nuclear factor of activated T-cells (NFAT) isoforms NFATc3 and NFATc4 in neurons.  J Biol Chem.  2012 September 12. 45:37594-37609.
[Link]

Maity B, Stewart A, Yang J, Loo L, Sheff D, Shepherd A, Mohapatra D, Fisher R.  Regulator of G protein signaling 6 (RGS6) protein ensures coordination of motor movement by modulating GABAB receptor signaling.  J Biol Chem.  2012 February 10. 287(7):4972-4981.
[Link]

Shepherd A, Mohapatra D.  Tissue preparation and immunostaining of mouse sensory nerve fibers innervating skin and limb bones.  J Vis Exp.  2012 January 26. 59:e3485.
[PubMed]

Shepherd A, Loo L, Gupte R, Mickle A, Mohapatra D.  Distinct modifications in Kv2.1 channel via chemokine receptor CXCR4 regulate neuronal survival-death dynamics..  J Neurosci.  2012. 32(49):17725-17739.
[Link]

Bocksteins E, Shepherd A, Mohapatra D, Snyders D.  Immunostaining of cell lines and neurons- key concepts and potential pitfalls.  In Immunocytochemistry.  2012. 

Loo L, Shepherd A, Mickle A, Lorca R, Shutov L, Usachev Y, Mohapatra D.  The C-type natriuretic peptide induces thermal hyperalgesia through a non-canonical Gβγ-dependent modulation of TRPV1 channel.  J Neurosci.  2012. 32(35):11942-11955.
[Link]

Bocksteins E, Labro A, Snyders D, Mohapatra D.  The electrically silent Kv6.4 subunit confers hyperpolarized gating charge movement in Kv2.1/Kv6.4 heterotetrameric channels.  PLoS One.  2012. 7(5):e37143.
[Link]

Walder R, Radhakrishnan R, Loo L, Rasmussen L, Mohapatra D, Wilson S, Sluka K.  TRPV1 is important for mechanical and heat sensitivity in uninjured animals and development of heat hyperalgesia after muscle inflammation.  Pain.  2012. 153(8):1664-1672.
[Link]

Yang J, Huang J, Maity B, Gao Z, Lorca R, Gudmundsson H, Li J, Stewart A, Swaminathan P, Ibeawuchi S, Shepherd A, Chen C, Kutschke W, Mohler P, Mohapatra D, Anderson M, Fisher R.  RGS6, a modulator of parasympathetic activation in heart.  Circ Res.  2010 November 26. 107(11):1345-1349.
[Link]

Kalashnikova E, Lorca R, Kaur I, Barisone G, Li B, Ishimaru T, Trimmer J, Mohapatra D, Díaz E.  SynDIG1: an activity-regulated, AMPA- receptor-interacting transmembrane protein that regulates excitatory synapse development.  Neuron.  2010 January 14. 65(1):80-93.
[Link]

Mohapatra D, Misonou H, Pan S, Held J, Surmeier D, Trimmer J.  Regulation of intrinsic excitability in hippocampal neurons by activity-dependent modulation of the KV2.1 potassium channel.  Channels (Austin).  2009. 3(1):46-56.
[Link]

Vacher H, Mohapatra D, Trimmer J.  Localization and targeting of voltage-dependent ion channels in mammalian central neurons.  Physiol Rev.  2008 October. 88(4):1407-1447.
[Link]

Mohapatra D, Siino D, Trimmer J.  Interdomain cytoplasmic interactions govern the intracellular trafficking, gating, and modulation of the Kv2.1 channel.  J Neurosci.  2008 May 7. 28(19):4982-4994.
[Link]

Mohapatra D, Park K, Trimmer J.  Dynamic regulation of the voltage-gated Kv2.1 potassium channel by multisite phosphorylation.  Biochem Soc Trans.  2007 November. 35(Pt 5):1064-1068.
[Link]

Mohapatra D, Vacher H, Trimmer J.  The surprising catch of a voltage-gated potassium channel in a neuronal SNARE.  Sci Signaling (Formerly Sci STKE).  2007 July 3. 2007(393):pe37.
[Link]

Vacher H, Mohapatra D, Misonou H, Trimmer J.  Regulation of Kv1 channel trafficking by the mamba snake neurotoxin dendrotoxin K.  FASEB J.  2007 March. 21(3):906-914.
[Link]

Park K, Mohapatra D, Trimmer J.  Proteomic analyses of K(v)2.1 channel phosphorylation sites determining cell background specific differences in function.  Channels (Austin).  2007. 1(2):59-61.
[Link]

Leffler A, Reiprich A, Mohapatra D, Nau C.  Use-dependent block by lidocaine but not amitriptyline is more pronounced in tetrodotoxin (TTX)-Resistant Nav1.8 than in TTX-sensitive Na+ channels.  J Pharmacol Exp Ther.  2007 January. 320(1):354-364.
[Link]

Misonou H, Menegola M, Mohapatra D, Guy L, Park K, Trimmer J.  Bidirectional activity-dependent regulation of neuronal ion channel phosphorylation.  J Neurosci.  2006 December 27. 26(52):13505-13514.
[Link]

Park K, Mohapatra D, Misonou H, Trimmer J.  Graded regulation of the Kv2.1 potassium channel by variable phosphorylation.  Science.  2006 August 18. 313(5789):976-979 [KSP & DPM are co-first authors].
[Link]

Mohapatra D, Trimmer J.  The Kv2.1 C terminus can autonomously transfer Kv2.1-like phosphorylation-dependent localization, voltage-dependent gating, and muscarinic modulation to diverse Kv channels.  J Neurosci.  2006 January 11. 26(2):685-695.
[Link]

Misonou H, Mohapatra D, Menegola M, Trimmer J.  Calcium- and metabolic state-dependent modulation of the voltage-dependent Kv2.1 channel regulates neuronal excitability in response to ischemia.  J Neurosci.  2005 November 30. 25(48):11184-11193.
[Link]

Misonou H, Mohapatra D, Trimmer J.  Kv2.1: a voltage-gated k+ channel critical to dynamic control of neuronal excitability.  Neurotoxicology.  2005 October. 26(5):743-752.
[Link]

Mohapatra D, Nau C.  Regulation of Ca2+-dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase.  J Biol Chem.  2005 April 8. 280(14):13424-13432.
[Link]

Misonou H, Mohapatra D, Park E, Leung V, Zhen D, Misonou K, Anderson A, Trimmer J.  Regulation of ion channel localization and phosphorylation by neuronal activity.  Nat Neurosci.  2004 July. 7(7):711-718.
[Link]

Mohapatra D, Nau C.  Desensitization of capsaicin-activated currents in the vanilloid receptor TRPV1 is decreased by the cyclic AMP-dependent protein kinase pathway.  J Biol Chem.  2003 December 12. 278(50):50080-50090.
[Link]

Mohapatra D, Wang S, Wang G, Nau C.  A tyrosine residue in TM6 of the Vanilloid Receptor TRPV1 involved in desensitization and calcium permeability of capsaicin-activated currents.  Mol Cell Neurosci.  2003 June. 23(2):314-324.
[Link]

Singh S, Mohapatra D, Sivakumar R.  Successful replacement of fetal calf serum with human urine for in vitro culture of Leishmania donovani.  J Commun Dis.  2000 December. 32(4):289-294.
[Link]

Date Last Modified: 07/02/2014 - 13:14:59