Department of Regenerative Medicine and Cell Biology

Michael J. Kern, Ph.D.
Associate Professor

Room 638, Basic Science Building
Office: (843) 792-1774
Lab: (843) 792-1782



BA Biology Thomas More College 1983
PhD Microbiology University of Kentucky 1990
Postdoctoral Fellow at University of Cincinnati

Research Interests:

Almost 1 baby in 100 born in the USA has congenital heart defects. A more thorough understanding of the molecular events of heart development will enhance diagnosis, prevention, and treatment of both childhood and adult heart diseases. I have been working on two genes, Prx1 and Prx2, that appear to be very important for cardiac development/function in mammals. I have created a strain of mice with the Prx2 gene inactivated using a process called gene targeting. My collaborators have performed the same technique to create mice with the Prx1 gene inactivated. These mice will facilitate the determination of the individual roles of Prx1 and 2 as well as any overlapping function in cardiac development. The mutant mice will also enhance the identification of the genetic circuitry of cardiac development and connect specific gene regulation with specific morphological or functional defects. A futuristic goal is to make a chart of cardiac development in which all the genes necessary for heart formation are connected with arrows representing positive or negative gene regulation.

In order to understand the genetic pathways of cardiac development I have focused on the murine homeobox genes, Prx1 (a.k.a. mHox, K-2, and Pmx) and Prx2 (a.k.a. S8). These genes encode DNA binding transcription factors and are members of the homeobox gene family. The importance of these genes is that they regulate other genes during cardiac development and thus are integral components of the genetic interactions, Ògene circuitryÓ, that determines the final form and function of the heart. Both genes are expressed very early in heart development, and later become restricted to the Òvalves and fibrous skeleton of the heart." They are also expressed in the adult heart and may play a role in adult heart disease. Analyzing how the heart develops in mice that do not contain the Prx1 and/or Prx2 genes will establish the role of the these two genes in the cardiac development. Preliminary data demonstrates that the Prx2 mutant adult mice have altered cardiac function. These mice may also be a good model for subtle developmental defects which compromise the function of the adult heart.

Current and future research interests:

(1.) Examine the regulation of the Prx1 and 2 genes. I am identifying and characterizing the promoter of the two genes. The promoter sequences will be compared to identify common elements that could be the binding site for transcription factors that would regulate both genes. Since both genes are similarly expressed in the heart this comparison may identify DNA binding sites for heart specific regulatory proteins. The regulation of these genes will be analyzed by transgenic mice and/or transfection studies.

(2.) Isolate and characterize gene(s) that are altered in expression within the mutant hearts. This identification is of primary importance to understand the cardiac phenotype of the mutant mice as well as the normal role of these transcription factors in cardiac development. I am using recently developed molecular genetic techniques to isolate mRNA transcripts altered in the mutant mice. cDNA and genomic clones will then be isolated and characterized. The pattern of expression in the mutants and wild type mice will be determined. Any gene that is altered in expression in the mutants is an excellent candidate for direct regulation by the Prx1 and/or Prx2 transcription factors. I will evaluate direct regulation by mobility shift assays, transfection studies, and transgenic mice analysis.

(3.) Determine if there is functional compensation during cardiac development between the Prx1 and 2 genes. The cardiac expression pattern of the Prx1 and Prx2 genes are very similar especially in the cushions/valves. These genes are also very similar in size, organization, polypeptide encoded (64% identity, 97% identity within the homeodomain), and even the DNA sequence that the polypeptide binds in vitro. I am interbreeding the two different strains of mutant mice and analyzing the progeny. The embryonic cardiac development of the mutants are being examined by traditional histological methods as well as by newer techniques such as confocal microscopy. The confocal microscopy evaluation consists of determining mitotic indices, Ca++ wave propagation, and 3-D reconstruction of mutant hearts. The department has a modern imaging facility complete with confocal microscope, Silicon Graphics software, and Power Macintosh computers for 3-D analysis of the data. The mutants will also be analyzed by the departmental scanning and transmission electron microscopes. These analyses will define the morphological development of mice that have the Prx1 and/or Prx2 genes deleted.

Congenital heart defects in infants and adult cardiac diseases are a major cause of mortality. A more thorough understanding of the molecular mechanisms of heart development/function will enhance diagnosis, prevention, and treatment of both childhood and adult heart diseases. The work in my lab lays the foundation for identifying genes and gene circuits involved in cardiac development/function.

Recent Publications:

  1. Pruett, N. D., Z. Hajdu, J. Zhang, R. P. Visconti, M. J. Kern, D. M. Wellik, M. W. Majesky and A. Awgulewitsch. "Changing Topographic Hox Expression in Blood Vessels Results in Regionally Distinct Vessel Wall Remodeling." Biol Open 1, no. 5 (2012): 430-5.
  2. Potter, K. A., M. J. Kern, G. Fullbright, J. Bielawski, S. S. Scherer, S. W. Yum, J. J. Li, H. Cheng, X. Han, J. K. Venkata, P. A. Khan, B. Rohrer and H. Hama. "Central Nervous System Dysfunction in a Mouse Model of Fa2h Deficiency." Glia 59, no. 7 (2011): 1009-21.
  3. Potter, C. S., N. D. Pruett, M. J. Kern, M. A. Baybo, A. R. Godwin, K. A. Potter, R. L. Peterson, J. P. Sundberg and A. Awgulewitsch. "The Nude Mutant Gene Foxn1 Is a Hoxc13 Regulatory Target During Hair Follicle and Nail Differentiation." J Invest Dermatol 131, no. 4 (2011): 828-37.
  4. Kuo, J., C. Shi, S. Cisewski, L. Zhang, M. J. Kern and H. Yao. "Regional Cell Density Distribution and Oxygen Consumption Rates in Porcine Tmj Discs: An Explant Study." Osteoarthritis Cartilage 19, no. 7 (2011): 911-8.
  5. Gruber, H. E., R. A. Norris, M. J. Kern, G. L. Hoelscher, J. A. Ingram, N. Zinchenko and E. N. Hanley, Jr. "Periostin Is Expressed by Cells of the Human and Sand Rat Intervertebral Discs." Biotech Histochem 86, no. 3 (2011): 199-206.
  6. Norris RA, Potts JD, Yost MJ, Junor L, Brooks T, Tan H, Hoffman S, Hart MM, Kern MJ, Damon B, Markwald RR, Goodwin RL. Periostin promotes a fibroblastic lineage pathway in atrioventricular valve progenitor cells.  Dev Dyn. 2009 May;238(5):1052-63.
  7. Alderson NL, Maldonado EN, Kern MJ, Bhat NR, Hama H. FA2H-dependent fatty acid 2-hydroxylation in postnatal mouse brain. J Lipid Res. 2006 Dec;47(12):2772-80. Epub 2006 Sep 23.
  8. Mitchell JM, Hicklin DM, Doughty PM, Hicklin JH, Dickert JW Jr, Tolbert SM, Peterkova R, Kern MJ. The Prx1 homeobox gene is critical for molar tooth morphogenesis. J Dent Res. 2006 Oct;85(10):888-93.
  9. Potter CS, Peterson RL, Barth JL, Pruett ND, Jacobs DF, Kern MJ, Argraves WS, Sundberg JP, Awgulewitsch A. Evidence that the satin hair mutant gene Foxq1 is among multiple and functionally diverse regulatory targets for Hoxc13 during hair follicle differentiation. J Biol Chem. 2006 Sep 29;281(39):29245-55. Epub 2006 Jul 10.
  10. Peterson RE, Hoffman S, Kern MJ. Opposing roles of two isoforms of the Prx1 homeobox gene in chondrogenesis. Dev Dyn. 2005 Jul;233(3):811-21.
  11. Scott KK, Norris RA, Potter SS, Norrington DW, Baybo MA, Hicklin DM, Kern MJ. GeneChip microarrays facilitate identification of Protease Nexin-1 as a target gene of the Prx2 (S8) homeoprotein. DNA Cell Biol. 2003 Feb;22(2):95-105.
  12. Mjaatvedt CH, Nakaoka T, Moreno-Rodriguez R, Norris RA, Kern MJ, Eisenberg CA, Turner D, Markwald RR. The outflow tract of the heart is recruited from a novel heart-forming field. Dev Biol. 2001 Oct 1;238(1):97-109.
  13. Chesterman ES, Kern MJ. Comparative analysis of Prx1 and Prx2 expression in mice provides evidence for incomplete compensation. Anat Rec. 2002 Jan 1;266(1):1-4.
  14. Norris RA, Kern MJ. The identification of prx1 transcription regulatory domains provides a mechanism for unequal compensation by the prx1 and prx2 loci. J Biol Chem. 2001 Jul 20;276(29):26829-37.
  15. Norris RA, Kern MJ. Identification of domains mediating transcription activation, repression, and inhibition in the paired-related homeobox protein, Prx2 (S8). DNA Cell Biol. 2001 Feb;20(2):89-99.
  16. Norris RA, Scott KK, Moore CS, Stetten G, Brown CR, Jabs EW, Wulfsberg EA, Yu J, Kern MJ. Protein, Nucleotide, OMIM Human PRRX1 and PRRX2 genes: cloning, expression, genomic localization, and exclusion as disease genes for Nager syndrome. Mamm Genome. 2000 Nov;11(11):1000-5.

Last updated on 27-Aug-2015

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