Printer Friendly

Dr. Alexander K. Murashov, M.D., Ph.D.

Associate Professor Graduate Director Physiology Department

Phone: (252) 744-3111
E-mail:murashoval@ecu.edu

Mailing Address:
Brody School of Medicine, 6N-74
600 Moye Blvd.
Greenville, NC 27834

Laboratory Homepage

Peripheral nerve injury
The peripheral nerve axons are unique in their robust regeneration capacity. A potential role for intra-axonal translation in axon regeneration is of particular interest, considering the fact that selected mRNAs are delivered to sites, that are long distances away from the neuronal cell body. Although axonally translated mRNAs are being identified with increasing frequency, the mechanisms regulating the localized protein synthesis remain largely unknown. We recently asked if axons in severed peripheral nerve have the potential to regulate local protein synthesis through the RNA interference (RNAi); highlighted in the FASEB Journal press release “Getting on your nerves ... and repairing them” 02/15/2007. Our work has shown that PNS axons in vivo and in vitro contain pivotal miRNA machinery proteins, including Dicer, Ago2, and FMRP. While a recent study uncovered a critical role for the miRNA pathway in regulation of actin filament dynamic and spine development in synapto-dendritic compartment, very little is known at present regarding the role of miRNA biogenesis within the axons. In our laboratory, we investigate the function of the miRNA machinery proteins and micro RNAs in PNS axons with particular focus on individual roles of miRNAs and key biosynthetic enzymes in regulation of intra-axonal translation and axonal regeneration. We employ a murine model of sciatic nerve crush to investigate axon remodeling. We examine the nerve from the level of axon function using electrophysiology to the mRNA and protein level using immunohistochemistry and genomic and proteomic analyses. We also perform cell culture and biochemical assays to help resolve mechanistic questions. Interested people may inquire about possible openings in the laboratory.

Spinal cord injury
Spinal cord injury (SCI) is often followed by chronic pain, which is persistent, intense and refractory to the currently available therapies. While the experiments over the last decade have demonstrated the involvement of a variety of endogenous factors limited success has been achieved in chronic pain treatment. Recent reports revealed a considerable therapeutic potential of embryonic stem (ES) cells. ES cells may be used to generate a variety of cells of adult organism and subsequently applied for treatment of human diseases including injuries of the nervous system. In spite of the recent progress in using ES cell to treat experimental SCI the mechanism of stem cell therapeutic action remains largely unknown. That is why, our long-range goal is to investigate molecular mechanisms of ES cell therapeutic action in the traumatically injured spinal cord. We have recently reported that transplantation of neuronal and glial precursors dramatically improves sensorimotor function after contusion injury. Moreover, our preliminary observations showed that ES cells predifferentiated into dorsal interneurons could restore sensory function and prevent development of chronic pain after SCI. Research from our laboratory indicates that transplantation of ES cells has neurotrophic effects, which can be observed as early as two days after transplantation. This neurotrophic action also persists for a long period, up to 60 days (last examined time point). The initial analyses revealed a decrease in levels of inflammatory cytokines, and increase in neurotrophic factors, and cyclic adenosine monophosphate (cAMP) two days after transplantation. These preliminary data let us to hypothesize that (a) ES cells, predifferentiated into dorsal interneurons, may provide upon transplantation anatomical, neurochemical and physiological recovery and prevent development of chronic pain; and (b) that the mechanism of therapeutic action of ES cells involves secretion of neurotrophins with subsequent activation of cAMP in the host tissue, promoting regeneration of axonal fibers. To verify our hypothesis, we are examining some of the signaling pathways activated in the host cells and stem cells after transplantation. Specifically, we are using the variations of co-culture experiments and molecular biological approaches to determine if there are correlative changes in cell survival and regeneration and the associated signaling pathways.

Associate Professor (2006-present)
Assistant Professor (1999-2006)
Department of Physiology
Brody School of Medicine at East Carolina University
Greenville, NC

Associate Research Scientist (1995-1999)
Postdoctoral Scientist (1992-1995)
Columbia University,
New York, NY, USA

NHMRC Research Officer (1990-1992)
Griffith University
Brisbane, Australia

Visiting Scientist (1990)
Howard Florey Institute of Experimental Physiology and Medicine
University of Melbourne
Australia

Group Leader, Stress Physiology (1988-90)
P.K. Anokhin Institute of Normal Physiology
Academy of Medical Sciences
Moscow, Russia

Assistant Professor (1987-1988)
Department of Normal Physiology,
Sechenov 1st Medical Institute,
Ministry of Health,
Moscow, Russia

Doctor of Philosophy in Physiology (1987)
P.K. Anokhin Institute of Normal Physiology
Academy of Medical Sciences
Moscow, Russia

Doctor of Medicine in Pediatrics (1983)
N.I. Pirogov 2nd Moscow Medical Institute
Ministry of Health
Moscow, Russia

Leah, J.D., Sandkuhler, J., Herdegen, T., Murashov, A., and Zimmermann, M. Potentiated Expression of FOS Protein in the Rat Spinal Cord Following Bilateral Noxious Cutaneous Stimulation. Neuroscience, 1992, vol.48, No.3, p.525-532

Leah, J.D., Herdegen, T., Murashov, A., Dragunow, M., Bravo, R.  Expression of immediate early gene proteins following axotomy and inhibition of axonal transport in the rat central nervous system.  Neuroscience, 1993, vol.57, No.1, p.53-66.

Wolgemuth D.J. and Murashov A.K. Models and molecular approaches to assessing the effects of the Microgravity environment on vertebrate development. The ASGSB Bulletin, 1995, 8(2), 63-71.

Murashov, A.K. and Wolgemuth D.J. Distinct transcripts are recognized by sense and antisense riboprobes for a member of the murine hsp70 gene family, hsp70.2, in various reproductive tissues. Molecular Reproduction and Development, 1996, 43: 17-24.

Murashov, A.K. and Wolgemuth D.J. Sense and antisense transcripts of the developmentally regulated murine hsp70.2 gene are expressed in distinct and only partially overlapping areas in the adult brain. Molecular Brain Research, 1996, 37: 85-95.

Murashov, A.K., Talebian, S. and Wolgemuth, D.J. Role of stress protein hsp25 in the response of orofacial nuclei motor system to physiological stress. Molecular Brain Research, 1998, 63, 14-24.

Murashov, A.K., Ul Haq, I., Hill, C., Park, E., Smith, M., Wang, X., Wang, X-Y., Goldberg, D.J. and Wolgemuth, D.J. Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury.  Molecular Brain Research, 2001, Vol 93/2, pp 199-208

Islamov, R.R., Hendricks, W.A., Jones, R.J., Lyall, G.J., Spanier, N.S. and Murashov, A.K.  17β-Estradiol stimulates regeneration of sciatic nerve in female mice. Brain Research, 2002, vol. 943/2, 283-286.

Smith M. , Wang X. ,Wolgemuth D.J., and Murashov A.K.  Development of the Mouse Vestibular System in the Absence of Gravity Perception.  Developmental Brain Research, 2003, Vol 140, pp 133–135

Islamov, R.R., Hendricks, W.A., Katwa, L.C., McMurray, R.J., Pak, E.S., Spanier, N.S. and Murashov, A.K. Effect of 17β-estradiol on gene expression in lumbar spinal cord following sciatic nerve crush injury in ovariectomized mice. Brain Research, 2003, Mar 14;966(1):65-75

McMurray, R.J., Islamov, R.R., Murashov, A.K.  Raloxifene Analog LY117018 Enhances the Regeneration of Sciatic Nerve in Ovariectomized Female Mice.  Brain Research, 2003, Vol 980/1 pp 140-145

Islamov, R.R., Chintalgattu, V., McMurray, R.J., Pak, E.S., Murashov, A.K., Katwa, L.C.  Differential expression of endothelin receptors in regenerating spinal motor neurons in mice.  Molecular Brain Research, 2003, Vol 116/1-2 pp 165-169.

Hoane, M.R., Becerra, G.D., Shank, J.E., Tatko, L., Pak E.S., Smith M. &Murashov, A.K.  Transplantation of Neuronal and Glial Precursors Dramatically Improves Sensorimotor Function but not Cognitive Function in the Traumatically Injured Brain.   Journal of Neurotrauma, 2004, Volume 21, Number 2, 163-174

Murashov, A.K., Islamov, R.R., McMurray, R.J., Pak, E.S., Weidner, D.A. Estrogen Increases Retrograde Labeling of Motoneurons: Evidence of a Non-Genomic Mechanism.  AJP- Cell Physiology, 2004, Aug;287(2):C320-6

Murashov,A.K., Pak, E.S., Hendricks,W.A., Tatko, L.M.  17b- Estradiol Enhances Neuronal Differentiation of Mouse Embryonic Stem Cells.  FEBS Letters, 2004.  Vol 569/1-3 pp 165-168.

Islamov, R.R., Chintalgattu, V., Pak, E.S., Katwa, L.C. and Murashov, A.K.  Induction of VEGF and its Flt-1 Receptor after Sciatic Nerve Crush Injury.  NeuroReport, 2004, 15(13):2117-2121.

Murashov, A. K., E.S. Pak, W. A. Hendricks, J.P. Owensby, P. L. Sierpinski, L.M. Tatko and P.L. Fletcher.  Directed Differentiation of Embryonic Stem Cells into Dorsal Interneurons.  The FASEB Journal, 2005 Feb;19(2):252-4.

Murashov AK, Pak ES, Katwa LC. Parallel Development of Cardiomyocytes and Neurons in Embryonic Stem Cell Culture. Biochemical and Biophysical Research Communications, 2005, Vol 332/3, pp 653-656

Glazova M, Aho TL, Palmetshofer A, Murashov A, Scheinin M, Koskinen PJ.
Pim-1 kinase enhances NFATc activity and neuroendocrine functions in PC12 cells.
Brain Res Mol Brain Res. 2005 Aug 18;138(2):116-23.

Islamov RR, Murashov AK, Chelyshev IuA. Protein synthesis in the axon.  Morfologiia. 2005;128(6):70-6. Review. Russian.

Olga Kokiko; Alexander Murashov, M.D., Ph.D.; Michael R Hoane  Administration of Raloxifene Reduces Sensorimotor and Working Memory Deficits Following Traumatic Brain Injury in the rat.  Behavioural Brain Research, 2006, Jun 30;170(2):233-40.

Wesley A. Hendricks, Elena S. Pak, J. Paul Owensby, Kristie J. Menta, Margarita Glazova, Justin Moretto, Sarah Hollis, Kori L. Brewer and Alexander K. Murashov  Pre-differentiated Embryonic Stem Cells Prevent Chronic Pain Behaviors and Restore Sensory Function Following Spinal Cord Injury in Mice.  Molecular Medicine, 2006, 12(1-3):34-46

A.K. Murashov, V.Chintalgattu, R.R. Islamov, T.E. Lever, E.S. Pak, P.L. Sierpinski, L.C. Katwa, and M.R. Van Scott  RNAi Pathway is Functional in Peripheral Nerve Axons.  The FASEB Journal, 2007 Mar;21(3):656-70. Epub 2007 Jan 5.

Becerra GD, Tatko LM, Pak ES, Murashov AK, Hoane MR.  Transplantation of GABAergic neurons but not astrocytes induces recovery of sensorimotor function in the traumatically injured brain.  Behav Brain Res. 2007 Apr 16;179(1):118-25. Epub 2007 Feb 1.