Michal Hetman, M.D., Ph.D.

Photo of Michal Hetman, PhD
  1. Professor, Department of Neurological Surgery and Department of Pharmacology & Toxicology
  2. Endowed Professor of Molecular Signaling


Laboratory of Neurosignalling

Telephone: 502-582-8060
E-mail Michal Hetman

Research Focus:

Pathologies of the nervous system including  traumatic injuries and neurodegenerative diseases are accompanied by neuronal cell death and dysfunction. The resulting loss of cell bodies, synapses, and cellular processes is thought to underlie neurological deficits occurring in these conditions. Therefore, therapeutic interventions to enhance neuronal survival and to preserve their morphological complexity may prevent development of deleterious neurological symptoms. Conversely, excessive growth of neurons may also lead to pathologies including epilepsy or neuropathic pain. The research in my laboratory is concentrated on identification of molecules controlling neural cell survival and  growth. My particular interests are in the role of a nuclear substructure, the nucleolus in stress sensing and cell growth in the nervous system. I am also interested in identifying signaling pathways that are critical for neural cell survival and growth control.

    Click to view all of Dr. Graves's publications on PubMed

    Key Publications:

    Hetman M., K. Kanning, J.E. Cavanaugh, Z. Xia. Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular-signal-regulated kinase and phosphatidylinositol-3 kinase. (1999)J. Biol. Chem. 274: 22569-22580

    Hetman M., J.E. Cavanaugh, D.Kimelman and Z.Xia. Role of Glycogen Synthase Kinase 3 beta in neuronal apoptosis induced by trophic withdrawal.(2000) J.Neurosci. 20: 2567-2574.

    Hetman M., S.L. Hsuan, A. Habas, M.J. Higgins, Z. Xia. ERK 1/2 antagonizes glycogen synthase kinase 3β –induced apoptosis in cortical neurons. (2002)J. Biol. Chem. 277:49577-49584.

    Szatmari E., A. Habas, P. Yang, J.J. Zheng, T. Hagg, M. Hetman. A positive feedback loop between glycogen synthase kinase 3β and protein phosphatase 1 after stimulation of NR2B NMDA receptors in forebrain neurons. (2005)J. Biol. Chem. 280:37526-37535.

    Kalita K., G. Kharebava, J. Zheng, M. Hetman. Role of MKL1 in ERK1/2-dependent stimulation of SRF-driven transcription in response to BDNF or increased synaptic activity.(2006)J. Neurosci.26:10020-10032

    Szatmari E.,  K. Kalita, G. Kharebava, M. Hetman. Role of kinase supressor of Ras-1 in neuronal survival signaling by extracellular signal-regulated kinase 1/2. (2007)J. Neurosci.27:11389-11400.

    Kalita K., D. Makonchuk, C. Gomes, J.J. Zheng, M. Hetman. Inhibition of nucleolar transcription as a trigger for neuronal apoptosis. (2008)J. Neurochem. 105:2286–2299.

    Kharebava G, D. Makonchuk, K. Kalita, J.J. Zheng, M. Hetman (2008) Requirement of 3-phosphoinositide-dependent protein kinase-1 (PDK1) for BDNF-mediated neuronal survival. J. Neurosci. 28(44):11409-11420.

    Vashishta A., A. Habas, P. Prunsiild, J.J. Zheng, T. Timmusk, M.Hetman (2009) Nuclear Factor of Activated T cells isoform c4 (NFATc4/NFAT3) as a mediator of anti-apoptotic transcription in NMDAR-stimulated cortical neurons. J. Neurosci.29:15331-15340. PMID: 19955386

    Gomes C., S.C. Smith, M. Yousef, J.J. Zheng, M. Hetman (2011) RNA-Polymerase-1-driven transcription as a mediator of Brain-Derived Neurotrophic Factor (BDNF)-induced neurite outgrowth. J. Biol. Chem.286:4357-63

    Pietrzak M., S.C. Smith, J.T. Geralds, T. Hagg, C. Gomes, M. Hetman (2011) Nucleolardisruption and apoptosis are distinct neuronal responses to etoposide-induced DNAdamage. J. Neurochem. 117:1033-1046, PMID: 21517844.

    Ohri S.S., M.A. Maddie, Y. Zhao, M.S. Qiu, M. Hetman, S.R. Whittemore (2011) Attenuating the endoplasmic reticulum stress response improves functional recovery after spinal cord injury. Glia. 59:1489-502, PMID: 21638341.

    Pietrzak M., G. Rempala, P.T. Nelson, J.J. Zheng, M. Hetman (2011) Epigenetic silencing of nucleolar rRNA genes in Alzheimer’s disease. PLoS ONE 6(7): e22585. doi:10.1371/journal.pone.0022585

    Smith S.C., A.R. Robinson, L.J. Niedernhofer, M. Hetman(2012) Downregulation of cholesterol biosynthesis genes in the forebrain of ERCC1-deficient mice. Neurobiol Dis. 45(3):1136-44. PubMed PMID: 22245387.

    Hetman M., M. Pietrzak (2012) Emerging roles of the neuronal nucleolus. Trends Neurosci. 35(5):305-314, PMID: 22305768.

    Ohri S.S., M. Hetman, S.R. Whittemore (2013) Restoring endoplasmic reticulum homeostasis improves functional recovery after spinal cord injury. Neurobiol Dis. 58:29-37, PubMed PMID: 23659896.

    Hallgren J., M. Pietrzak, G. Rempala, P.T. Nelson, M. Hetman(2014) Neurodegeneration-associated instability of ribosomal DNA. Biochim Biophys Acta. 1842(6):860-868, PMID: 24389328.

    Vashishta A, M.Hetman(2014) Inhibitors of Histone Deacetylases Enhance Neurotoxicity of DNA Damage. Neuromolecular Med. 16(4):727-741, PMID: 25063076.

    Kilanczyk E., A.Filipek, M.Hetman(2014) Calcyclin-binding protein/Siah-1-interacting protein as a regulator of transcriptional responses in brain cells. J Neurosci Res. 93(1):75-81, PMID: 25163685.