Christine B. Kern, Ph.D.
Room 647, Basic Science Building
Office: (843) 792-9618
Lab: (843) 792-4279
BA Biology, Hope College, Holland MI 1985
PhD Microbiology and Immunology, University of Kentucky 1992
Postdoctoral Fellow at University of Cincinnati (J. Lingrel, PhD)
I am interested in the formation and homeostasis of the extracellular matrix (ECM) architecture, i.e. the proteins and molecules that make up the outside environment of cells. The connective tissue in the body that serves to connect different tissues together and provide a framework of support is comprised largely of ECM components. My primary areas of interests are cardiovascular development and disease. The long-term goal of our laboratory is to identify novel therapeutic targets for the treatment of cardiovascular disease.
Adult cardiac valve disease affects up to 5% of Americans with approximately 25% of the aged population developing aortic valve sclerosis, a marker of valve disease. The fact that most diseased valves have an underlying malformation suggests that determining the etiology of valve diseases lies in the discovery of novel mechanisms and genes that are involved in valve development. A hallmark of both developmental and adult disease is the loss of an organized, stratified ECM. My current research interests center around our findings that have revealed that the ADAMTS proteases are critical for ECM remodeling that occurs during cardiac valve development as well as the formation of the arterial walls of the aortic and pulmonary arteries. Since we are interested in elucidating the biomechanical circuitry we primarily focus on in-vivo studies that involve mouse models, confocal imaging and molecular biology techniques to test our hypotheses. Additional ex-vivo approaches are utilized to further investigate mechanistic pathways.
Our current studies investigate the interconnection of ECM remodeling, with cell behavior and signaling in an area of valve development and disease where very few investigators are focused and that is extremely relevant to valve dysfunction. Mouse models used in our laboratory serve as a unique models to study the progression of myxomatous valve disease, and development of bicuspid aortic valves that we eventually will utilize to test future therapeutics designed to ameliorate cardiac valve disease.
Recently our laboratory has also been involved with the investigation of the Small Leucine Rich Proteoglycans referred to as SLRPs. Many SLRPs have roles in collagen assembly but have not been investigated thoroughly in the heart. Using genetically modified mouse models of SLRP deficiency we have begun to investigate the potential roles of these proteoglycans in cardiac development and disease.
One of the most rewarding aspects of my scientific career is providing opportunities in my laboratory to explore their scientific interest, potential and to gain professional life experience. I mentor undergraduates in the MUSC Student Undergraduate Research Program (SURP) and College of Charleston Students. I am also interested in educating and mentoring middle school and high school students in the public schools to encourage more career interest in the Science Technology Engineering and Math (STEM) careers. If you are interested in a research opportunity in my laboratory or collaborative educational interests please email.
In addition to lab mentoring I also teach histology to first year dental students and special topics seminars to graduate students at the Medical University of South Carolina.
I am currently seeking post-doctoral fellows that are applicable for a T32 Training Grant (Dr. Donald Menick, PI).
R01 HL121382 September 2014 -August 2018; Proteoglycan Regulation During Cardiac Valve Development and Homeostasis, Role: Principal Investigator
Selected Recent Publications:
- T.A. Burns, M.T. Zimmerman, D.R. Zimmerman, E.L. Krug, S. Comte-Walters, L.Reyes, M.A. Davis, K.L. Schey, J.H. Schwacke, C.B. Kern, C.H. Mjaatvedt. Imbalanced expression of Vcan mRNA splice form proteins alters heart morphology and cellular protein profiles. PLoS One. 2014 Feb 20;9(2):e89133.
- L.E. Dupuis LE and C.B. Kern. Small leucine rich proteoglycans exhibit unique spatiotemporal expression profiles during cardiac valve development. Developmental Dynamics 2014 Apr;243(4):601-11.
- L.E. Dupuis, H Osinska H, Weinstein MB, Hinton RB, Kern CB. Insufficient versican cleavage and Smad2 phosphorylation results in bicuspid aortic and pulmonary valves. Journal of Molecular and Cellular Cardiology 2013 Jul;60:50-9.
- M.A. Cooley, V.M. Fresco, M.E. Dorlon, W.O. Twal, N.V. Lee, J.L. Barth, C.B. Kern, M. L. Iruela-Arispe, and W.S. Argraves. Fibulin-1 is Required During Cardiac Ventricular Morphogenesis for Versican Cleavage, Suppression of ErbB2 and Erk1/2 Activation, and to Attenuate Trabecular Cardiomyocyte Proliferation, Developmental Dynamics, 2012 Feb241(2); 303-14.
- V. K. Krishnamurthy, A. M. Opoka, C. B. Kern, F. Guilak, D. A. Narmoneva, R. B. Hinton Maladaptive Matrix Remodeling and Regional Biomechanical Dysfunction in a Mouse Model of Aortic Valve Disease, Matrix Biology, 2012 Apr;31(3):197-205.
- L. Dupuis, D. R. McCulloch, J.D. McGarity, A. Bahn, A. Wessels, D. Weber, A. Megan Diminich, C.M. Nelson, S. S. Apte, C.B. Kern. Altered versican cleavage in ADAMTS5 deficient mice: A novel etiology of myxomatous valve disease. Developmental Biology 2011 Sep 1;357(1):152-64.
- R. Mukherjee, W.T. Rivers, J.M. Ruddy, R.G. Matthews, C.N. Koval, R.A. Plylar, E.I. Chang, R.K. Patal, C.B. Kern, R.E. Stroud, and F.G. Spinale. Long-Term Localized High-Frequency Electric Stimulation Within the Myocardial Infarct; Effects on Matrix Metalloproteinases and Regional Remodeling, Circulation 2010 Jul 6;122(1):20-32.
- C.B. Kern, A. Wessels, J. McGarity, L. Dixon, E. Alston, W.S. Argraves, D. Geeting, C.M. Nelson, D.R. Menick and S.S. Apte. Reduced versican cleavage due to Adamts9 haploinsufficiency is associated with cardiac and aortic anomalies, Matrix Biology, 2010 May; 29(4): 304-16. PMC2862783.
- S.K. Mani, E.A. Egan, B.K. Addy, M. Grimm, H. Kasiganesan, T. Thiyagarajan, L. Renaud, J.H. Brown, C.B. Kern and D. R. Menick. Beta-Adrenergic receptor stimulated Ncx1 upregulation is mediated via CaMKII/AP-1 signaling pathway in adult cardiomyocytes, J Mol Cell Cardiol, 2010 Feb;48(2):342-51. NIHMS165035.
- R. H. Anderson, R.P. Thompson and C. B. Kern. Development of aortic valves with 2 and 3 leaflets, Journal of the American College of Cardiology, 2009, Dec 8;54(24):2319-20.
- S. Chandrasekaran, R. E. Peterson, S. K. Mani, L. Renaud, A. L. Buchholz, B. Addy, L. Xu, T. Thiyagarajan, C. B. Kern and Donald R. Menick. Histone Deacetylases Facilitate Ncx1 Upregulation in Adult Cardiocytes 2009 Faseb Journal, Nov;23(11):3851-64.
- B. Snarr, C.B. Kern, and A. Wessels. Origin and Fate of Cardiac Mesenchyme, Developmental Dynamics 2008 Oct; 237 Jul (10): 2804-19.
- M. A. Cooley, C.B. Kern, V.M. Fresco, A. Wessels, R.P. Thompson, T. C. McQuinn, W. O. Twal, C. H. Mjaatvedt, C. J. Drake and W. S. Argraves. Fibulin-1 is required for morphogenesis of neural crest-derived structures, Developmental Biology 2008 15;319 (2):336-45.
- E.W Wirrig, B.S. Snarr, A. L. Phelps, J. L. Barth, V. M. Fresco C.B. Kern, C.H. Mjaatvedt, B. P. Toole, S. Hoffman, T.C. Trusk, W.S. Argraves, and A. Wessels. Cartilage Link Protein 1 (Crtl1), an extracellular matrix component playing an important role in heart developmental Developmental Biology 2007 Oct. 15;310(2):291-303.
- C.B. Kern, R.A. Norris, R.P. Thompson, W.S. Argraves, S.E. Fairey, L. Reyes, S. Hoffman, R.R. Markwald and C.H. Mjaatvedt Versican proteolysis mediates myocardial regression during outflow tract development. Developmental Dynamics 2007 Jan16;236(3):671-683.
- C.B. Kern, W.O. Twal, C.H. Mjaatvedt, S.E. Fairey, B.P. Toole, M.L. Iruela-Arispe and W.S. Argraves. Proteolytic Cleavage of Versican During Cardiac Cushion Morphogenesis. Developmental Dynamics 2006 Aug;235(8):2238-47.