Christine (Christi) 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 extracellular matrix (ECM) i.e. the proteins and molecules that make up the outside environment of cells. In adult tissues the ECM is often referred to as connective tissue since it serves to connect different tissue types together and provides a framework of support to organs. The specific class of ECM molecules that we are focused on is the proteoglycans; protein cores that are decorated with sugar moieties and that are also subject to proteolytic cleavage. The fact that the ECM is dynamic during development, wound healing and disease, is an aspect that is particularly interesting to my lab, and one where very few researchers are focused. Although my primary area of interest is cardiovascular development and disease my group is more recently involved in studies that investigate craniofacial biology.
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 development of the cardiac outlet i.e. the arterial walls of the aortic and pulmonary arteries and valves that ensure unidirectional blood flow. 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. We have developed unique models to study the progression of myxomatous valve disease, development of bicuspid aortic valves and anomalies of the ascending arterial walls. The long-term goal of my laboratory is to identify novel therapeutic targets for the treatment of disease.
Undergraduate Mentoring: 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 for independent study and bachelors essay research projects. In addition to regularly interviewing undergraduate students for research opportunities in my laboratory, I also interview and facilitate placement into other MUSC basic science laboratories.
High School Student Mentoring: I serve as a mentor for the Governor’s School of Math and Science, and as an intern advisor for the Charleston County School of the Arts.
If you are interested in a research opportunity in my laboratory or collaborative educational interests, please email: email@example.com
Dental Histology: I teach the topics related to extracellular matrix, and the cardiovascular system to first year dental students in the College of Dental Medicine.
Service Interests: I am a member of the Woman’s Scholarship Initiative, serving on the workshop committee and also mentoring women with altered career paths.
R01 HL121382 September 2014 -August 2018; Proteoglycan Regulation During Cardiac Valve Development and Homeostasis, Role: Principal Investigator
Selected Recent Publications:
- L. E. Dupuis, M. G. Berger, S. Feldman, L. Doucette, V. Fowlkes, S.Chakravarti, S. Thibaudeau, N. Alcala, A. D. Bradshaw and C. B. Kern*. Lumican Deficiency Results In Cardiomyocyte Hypertrophy With Altered Collagen Assembly. J. Mol. Cell. Cardiol. 2015 Jul;84:70-80 (Journal Cover awarded for image from this manuscript).
- S. Mani, C. B. Kern, D. Kimbrough, B. Addy, H. Kasiganesan, W. Rivers, R. Patel, J. Chou, F. Spinale, R. Mukherjee, and D. Menick "Inhibition of Class I Histone Deacetylase Activity Represses Matrix Metalloproteinase-2 and -9 Expression and Preserves LV Function Post Myocardial Infarction" American Journal of Physiology - Heart and Circulatory 2015 Jun 1;308(11):H1391-401
- K. Harikrishnan, M. A. Cooley, Y. Sugi, J. L. Barth, L. M. Rasmussen, C. B. Kern, K. M. Argraves, and W. S. Argraves. Fibulin-1 suppresses endothelial to mesenchymal transition in the proximal outflow tract. Mech Dev. 2015 Jan 6. pii: S0925-4773(14)00091-4. PMID: 25575930
- 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.