Pharmacology

Yuriy M. Usachev, PhD

Portrait

Associate Professor of Pharmacology
Associate Professor of Anesthesia

Contact Information

Primary Office: 2-450 Bowen Science Building
Iowa City, IA 52242
Primary Office Phone: 319-335-9388

Lab: 2-440 Bowen Science Building
Iowa City, IA 52242
Phone: 319-353-3887

Email: yuriy-usachev@uiowa.edu

Education

BS, Physics - Optics and Spectroscopy, Kiev State University, Kiev, Ukraine
MSc, Physics—Optics and Spectroscopy, Kiev State University, Kiev, Ukraine
PhD, Biology, International Center of Molecular Physiology, Bogomoletz Institute of Physiology, Kiev, Ukraine

Visiting Scientist, Department of Neurophysiology, Max-Planck-Institute of Psychiatry, Munich, Germany
Postdoctoral Fellow, The Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom
Research Scientist, International Center of Molecular Physiology, Bogomoletz Institute of Physiology, Kiev, Ukraine
Postdoctoral Fellow/Lecturer in Pharmacology, Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota

Education/Training Program Affiliations

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

Research Summary

Chronic pain management remains one of the most serious public health problems. We use an array of molecular biological and genetic techniques, combined with patch-clamp recordings and fluorescent imaging of intracellular Ca2+, Na+ and pH changes in pain-conducting neurons (called nociceptors), as well as behavioral studies to address two broad sets of questions related to chronic pain pathogenesis. The first set of questions focuses on relatively rapid changes to nociceptor excitability and synaptic transmission that are induced by proinflammatory mediators generated by immune and glial cells at the site of injury or inflammation, and mediated via phosphorylation of so-called pain channels, including TRPV1, TRPA1 and voltage-gated Na+ channels Nav1.7, 1.8 and 1.9. We are particularly interested in the role of the complement system factors C3a and C5a in regulating nociceptor excitability and function. The second set of questions examines the long-term changes to the nociceptor molecular composition and function in response to injury or inflammation, and involves alterations in gene expression. We particularly focus on the Ca2+-dependent transcription factor NFAT that regulates expression of a number of proteins implicated in pain sensitization, such as COX-2, BDNF, chemokine receptor CCR2 and several voltage-gated K+ channels. Another line of investigation focuses on the function of mitochondria in regulating neuronal plasticity and survival under conditions of stress or illness, such as hyperglycemia in diabetes or exposure to toxic concentrations of glutamate following ischemic stroke. In addition to generating energy, mitochondria play critical role in neuronal signaling, and particularly, in the regulation of Ca2+ homeostasis and Ca2+-dependent processes. Impaired mitochondrial Ca2+ regulation contributes to neuronal damage in stroke and neurodegenerative disorders. Mitochondria are highly dynamic organelles that can rapidly undergo fission and fusion, and the mitochondrial fission and fusion (MFF) balance can significantly impact dendritic and axonal morphogenesis, synaptic plasticity and neuronal survival. We use a multidisciplinary approach (electrophysiology, confocal microscopy, brain slice recordings, animal models of diabetes and stroke) to better understand regulatory mechanisms and function of mitochondrial Ca2+ transport in neurons, its dependence on the MFF status, and the role of mitochondrial Ca2+ and MFF in protecting neurons from glutamate toxicity as well as hyperglycemia-induced axonal degeneration.

Selected Publications

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Inagaki A, Frank A, Usachev Y, Benveniste M, Lee A.  Pharmacological correction of gating defects in the voltage- gated Cav2.1 Ca2+ channel due to a familial hemiplegic migraine mutation.  Neuron.  2014. 81:91-102.
[Link]

Shutov L, Kim M, Houlihan P, Medvedeva Y, Usachev Y.  Mitochondria and plasma membrane Ca2+ -ATPase (PMCA) control presynaptic clearance in capsaicin-sensitive rat sensory neurons.  Journal of Physiology.  2013. 591:2443-2462.
[Link]

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, Richerson G, Mohapatra D, Wemmie J, Bassuk A.  PRICKLE2 defects link the non-canonical Wnt pathway to autism.  Molecular Psychiatry.  2013. 18:1077-1089.
[Link]

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 November 2. 287(45):37594-37609.
[Link]

Loo L, Shepherd A, Mickle A, Lorca R, Shutov L, Usachev Y, Mohapatra D.  The C-Type Natriuretic Peptide Induces Thermal Hyperalgesia through a Noncanonical Gβγ-dependent Modulation of TRPV1 Channel.  J Neurosci.  2012 August 29. 32(35):11942-11955.
[Link]

Merrill R, Dagda R, Dickey A, Cribbs J, Green S, Usachev Y, Strack S.  Mechanism of neuroprotective mitochondrial remodeling by PKA/AKAP1.  PLoS Biol.  2011 April. 9(4):e1000612.
[Link]

Jenkins M, Christel C, Jiao Y, Abiria S, Kim K, Usachev Y, Obermair G, Colbran R, Lee A.  Ca2+-dependent facilitation of Cav1.3 Ca2+ channels by densin and Ca2+/calmodulin-dependent protein kinase II.  J Neurosci.  2010 April 14. 30(15):5125-5135.
[Link]

Jang J, Clark J, Li X, Yorel M, Usachev Y, Brennan T.  Nociceptive sensitization by complement C5a and C3a in mouse.  Pain.  2010 February. 148(2):343-352.
[Link]

Kim M, Usachev Y.  Mitochondrial Ca2+ cycling facilitates activation of the transcription factor NFAT in sensory neurons.  J Neurosci.  2009 September 30. 29(39):12101-12114.
[Link]

Medvedeva Y, Kim M, Schnizler K, Usachev Y.  Functional tetrodotoxin-resistant Na(+) channels are expressed presynaptically in rat dorsal root ganglia neurons.  Neuroscience.  2009 March 17. 159(2):559-569.
[Link]

Date Last Modified: 03/13/2014 - 11:00:08