Michal Hetman, Ph.D.

Education:Michal Hetman, Ph.D. 

MD., Medical University of Warsaw; 1993
Ph.D., neurobiology, Polish Academy of Sciences; 1997
Postdoctoral Fellowship, University of Washington; 1997-2000

Curriculum Vitae

Current Positions:

Professor of Neurological Surgery, and Pharmacology and Toxicology
Endowed Chair in Molecular Signalling

Contact Information: 

511 S. Floyd St, MDR 616
Louisville, KY40202
michal.hetman@louisville.edu

Website Link:

Kentucky Spinal Cord Injury Research Center - Laboratory of Neural Signaling

Research Description:

Our laboratory uses various molecular/cell neurobiology approaches to address two major questions.

Question #1: What is the contribution of a nuclear substructure, the nucleolus and the nucleolus-based process of ribosome biogenesis to the regulation of neuronal gene expression programs as well as neuronal damage response? We are particularly interested in mechanisms that underlie the requirement of neuronal ribosome synthesis for development and maintenance of the dendritic tree. In addition, we investigate the role of ribosomal biogenesis stress (also known as nucleolar stress) in immature neuron apoptosis that is triggered by neurotropic RNA viruses such as the Zika virus. As ribosomal biogenesis is often hijacked by cancer cells to fuel their growth, we also are looking into possible anti-cancer use of ribosome synthesis disruptors that underlie non-cancerous pathologies of the nervous system.

Question #2: What are the mechanisms that mediate loss and/or maladaptive changes in neural cells after traumatic spinal cord injury? Our efforts are focused on determining the role of the integrated stress response pathway in injury-induced death of oligodendrocytes, and, consequently, injury-associated loss of the spinal cord white matter. In addition, we also are interested in comprehensive analysis of gene expression programs that mediate oligodendrocyte- or sensory neuron responses to injury including identification of the master transcription factors driving such responses.

To answer those questions we use cultured cells (neurons, oligodendrocytes or neuroprogenitors from rats, mice or human induced pluripotent stem cells) as well as whole mice (both wild-type and various transgenic lines). Dendritic morphometry, apoptosis/cell survival analysis, mRNA/rRNA/protein expression analysis, DNA transfections, RNASeq, qRT-PCR, and immunofluorescence analysis are routinely applied to those experimental systems.

Selected publications with greatest relevance to our current research are listed below. Hetman lab trainees are underlined, summer students/rotating medical students and interns are indicated by *. The complete bibliography may be accessed with the following link:  Pubmed - M. Hetman.

Literature Cited:

Selected publications with greatest relevance to our current research are listed below. Hetman lab trainees are underlined, summer students/rotating medical students and interns are indicated by *.

  1.  Ohri SS, Bankston AN, Mullins SA, Liu Y, Andres KR, Beare JE, Howard RM, Burke DA, Riegler AS, Smith AE, Hetman M, Whittemore SR.  Blocking autophagy in oligodendrocytes limits functional recovery after spinal cord injury.  J Neuroscience 2018 May 23. pii: 0679-17. doi: 10.1523/JNEUROSCI.0679-17.2018. [Epub ahead of print] PMID: 29793971.
  2. Vashishta A, Slomnicki LP, Pietrzak M, Smith SC, Kolikonda M*, Naik SP*, Parlato R, Hetman M.  RNA Polymerase 1 is transiently regulated by seizures and plays a role in a pharmacological kindling model of epilepsy.  Molecular Neurobiology 2018 Mar 15. doi: 10.1007/s12035-018-0989-9. [Epub ahead of print] PMID: 29546592.
  3. Slomnicki LP, Hallgren J, Vashishta A, Smith SC, Ellis SR, Hetman M.  Proapoptotic requirement of ribosomal protein L11 in ribosomal stress-challenged cortical neurons.  Molecular Neurobiology 2018 Jan;55(1):538-53. doi: 10.1007/s12035-016-0336-y. Epub 2016 Dec 14. PMID: 27975169.
  4. Slomnicki LP, Chung DH, Parker A*, Hermann T*, Boyd NL, Hetman M.  Ribosomal stress and Tp53-mediated neuronal apoptosis in response to capsid protein of the Zika virus.  Scientific Reports 2017 Nov 30;7(1):16652. doi: 10.1038/s41598-017-16952-8.  PMID: 29192272. PMCID: PMC5709411.
  5. Kilanczyk E, Saraswat Ohri S, Whittemore SR, Hetman M.  Antioxidant protection of NADPH-depleted oligodendrocyte precursor cells is dependent on supply of reduced glutathione.  ASN Neuro 2016 Jul 21;8(4). pii: 1759091416660404. doi: 10.1177/1759091416660404. Print 2016 Aug. PMID: 27449129. PMCID: PMC4962338.
  6. Slomnicki LP, Malinowska A, Kistowski M, Palusinski A, Zheng JJ, Sepp M,Timmusk T, Dadlez M, Hetman M.  Nucleolar enrichment of brain proteins with critical roles in human neurodevelopment.  Molecular & Cellular Proteomics 2016 Jun;15(6):2055-75. doi: 10.1074/mcp.M115.051920. Epub 2016 Apr 6. PMID: 27053602; PMCID: PMC5083102.
  7. Slomnicki LP, Pietrzak M, Vashishta A, Jones J*, Lynch N*, Elliot S*, Poulos E*, Malicote D*, Morris BE*, Hallgren J, Hetman M.  Requirement of neuronal ribosome synthesis for growth and maintenance of the dendritic tree.  Journal of Biological Chemistry 2016 Mar 11;291(11):5721-39. doi: 10.1074/jbc.M115.682161. Epub 2016 Jan 12. PMID: 26757818. PMCID: PMC4786710.
  8. Hallgren J, Pietrzak M, Rempala G, Nelson PT, Hetman M.  Neurodegeneration-associated instability of ribosomal DNA.  Biochimica et Biophysica Acta 2014 Jun;1842(6):860-8. doi: 10.1016/j.bbadis.2013.12.012. Epub 2014 Jan 2. PMID: 24389328. PMCID: PMC3985612.
  9. Ohri SS, Hetman M, Whittemore SR.  Restoring endoplasmic reticulum homeostasis improves functional recovery after spinal cord injury.  Neurobiology of Disease 2013 Oct;58:29-37.  doi: 10.1016/j.nbd.2013.04.021. Epub 2013 May 6. PMID: 23659896. PMCID: PMC3748169.
  10. Hetman M, Pietrzak M.  Emerging roles of the neuronal nucleolus.  Trends in Neuroscience 2012 May;35(5):305-14. doi: 10.1016/j.tins.2012.01.002. Epub 2012 Feb 2. Review. PMID: 22305768. PMCID: PMC3348388.
  11. Ohri SS, Maddie MA, Zhao Y, Qiu MS, Hetman M, Whittemore SR.  Attenuating the endoplasmic reticulum stress response improves functional recovery after spinal cord injury.  Glia 2011 Oct;59(10):1489-502. doi: 10.1002/glia.21191. Epub 2011 Jun 2. PMID: 21638341. PMCID: PMC3391751.
  12. Gomes C, Smith SC, Youssef MN*, Zheng JJ, Hagg T, Hetman M.  RNA polymerase 1-driven transcription as a mediator of BDNF-induced neurite outgrowth.  Journal of Biological Chemistry 2011 Feb 11;286(6):4357-63. doi: 10.1074/jbc.M110.170134. Epub 2010 Nov 23. PMID: 21098478. PMCID: PMC3039349.
  13. Pietrzak M, Rempala G, Nelson PT, Zheng JJ, Hetman M.  Epigenetic silencing of nucleolar rRNA genes in Alzheimer's disease.  PLoS One 2011;6(7):e22585. doi: 10.1371/journal.pone.0022585. Epub 2011 Jul 22. PMID: 21799908. PMCID: PMC3142181.
  14. Kalita K, Makonchuk D, Gomes C, Zheng JJ, Hetman M.  Inhibition of nucleolar transcription as a trigger for neuronal apoptosis.  Journal of Neurochemistry 2008 Jun 1;105(6):2286-99. doi: 10.1111/j.1471-4159.2008.05316.x. PMID: 18315559. PMCID: PMC2909334.

PubMed Information