Christine (Christi) B. Kern, Ph.D.
Room 647, Basic Science Building
Office: (843) 792-9618
Lab Phone: (843) 792-4279
More information about the Christi Kern Lab
Education:BA Biology, Hope College, Holland MI 1985
PhD Microbiology and Immunology, University of Kentucky 1992
Post-doctoral Fellow, University of Cincinnati, J. Lingrel, PhD
The C. Kern lab is interested in the extracellular matrix (ECM) i.e. the proteins and molecules that make up the environment of cells, in the context of cardiovascular and temporomandibular joint development and disease. Our focus is on the proteoglycans; protein cores that are decorated with sugar moieties and that are also cleaved. Since the ECM architecture is a reflection of the biomechanical forces that the tissues endure, the majority of our research uses mouse models. We are also interested in how some developmental programs that involved ECM regulation are reactivated in adult degenerative diseases.
I. Cardiovascular Development: The C. Kern lab investigates the development of the cardiac outflow tract; the region of the developing heart that gives rise to the aortic and pulmonary valves as well as the ascending aortic and pulmonary arteries. Approximately 1:100 babies are born with a heart defect and the majority of these defects arise from abnormal development of the cardiac outflow tract. We are utilizing mouse models that we have previously characterized that exhibit significant changes in the proteolytic cleavage of a key proteoglycan, versican (Vcan). The failure to cleave Vcan leads to a number of cardiovascular defects in the outflow tract that have clinical relevance. Published research from our laboratory demonstrated that loss of the ADAMTS5 protease that cleaves Vcan resulted in cardiac valve defects in 100% of Adamts5-/- mice.
Figure 1: Loss of ADAMTS5-Mediated Vcan Cleavage Results in Cardiac Valve Defects. The intact Vcan molecule is represented with the chondroitin sulfate side chains (purple). A-The site of ADAMTS cleavage is depicted by the Packman™ and the green triangle. Vcan is cleaved by ADAMTS5 and the cleaved Vcan is represented on the right. B-Image on the right shows ‘intact’ Vcan immunolocalization (green) in the cardiac valve cusps. In the Adamts5-/- valve cusps there in an increase in the amount of Vcan immunolocalization (green); there is an increase in the size and the shape of the Adamts5-/- cusps is also altered. Modified from Dupuis et. al., Dev Biol 2011.
Bicuspid aortic valves are comprised of two rather than three cusps and occur in 1-2% of the population placing them at higher risk of developing progressive aortic valve disease and ascending aortic aneurysms. We discovered that mice deficient for the ECM protease ADAMTS5, (Adamts5-/-) that cleaves versican, that also have a reduction in Smad2, have highly penetrant (>75%) bicuspid aortic and pulmonary valves. We have generated a model of cardiac valve development that depicts the dependence on the proteolytic cleavage of Vcan. In our lab studies are underway to determine the origin of bicuspid valve defects. We are also investigating the consequence of altered proteoglycan composition to the adult arterial walls and cardiac valves in mouse models of disease.
Figure 2: Schematic of aortic and pulmonary valve development and disruption in Adamts5-/- and Adamts5-/-;Smad2+/- mice with valve malformations. Whole hearts (A) depict the orientation in B and C; Models of normal (wild type) (B) and ADAMTS5 deficient (C) development of outflow tract. Versican, intact (royal blue) or cleaved in cyan. Pink- transient septum; Yellow- collagen; White arrows show fusion of cushions in bicuspid malformations. Black arrowheads-regions of excavation. Red-transient myocardium; Orange- arterial wall, LC- lateral outflow tract cushion; IC-intercalated cushion. Dupuis et. al., JMCC 2011.
II. Temporomandibular Joint Development (TMJ): Recently the C. Kern lab in collaboration with Dr. Hai Yao has begun investigating the development of the TMJ using rodent models. We are specifically interested in how proteoglycan turnover impacts joint development and defining physiological roles for the ADAMTS proteases. The TMJ is comprised of fibrocartilage, which is relatively understudied compared to hyaline cartilage that comprises the knee joints.
Cover Image Awarded: Dupuis et.al., JMCC 2015: Three dimensional reconstruction of a mouse heart, blue depicts muscle tissue and red, the lumen spaces. Right side of image is high magnification of cardiomyocytes (blue) within the ventricle and green staining shows the collagen-rich ECM surrounding cardiomyocytes; Red-nuclei.
Undergraduate Mentoring: One of the most rewarding aspects of Dr. Christi Kern’s scientific career is providing opportunities in my laboratory to students to explore their scientific interest, potential and to gain professional life experience. Dr. Kern mentors undergraduates in the MUSC Student Undergraduate Research Program (SURP) and College of Charleston Students for independent study and bachelors essay research projects. In addition she also interviews and facilitates placements of students in other MUSC basic science laboratories. If you are interested in undergraduate research email Dr. Kern: firstname.lastname@example.org
R01 HL121382 September 2014 -August 2018; Proteoglycan Regulation During Cardiac Valve Development and Homeostasis, Role: Principal Investigator
Pilot Project, Center for Oral Health Research (COHR) June 1 2016 “Biomechanical forces and extracellular matrix remodeling in TMJ pathogenesis”, Role: Principal Investigator
- L.E. Dupuis, L. Doucette, A. Kittrell Rice, A. E. Lancaster, M. G. Berger, S. Chakravarti, and C. B. Kern. Development of Myotendinous-like Junctions That Anchor Cardiac Valves Requires Fibromodulin and Lumican. Dev. Dynamics 2016 accepted for publication.
- V. M. Fresco, C. B. Kern, M. Mohammadi and W. O. Twal. Fibulin-1 Binds to Fibroblast Growth Factor 8 With High Affinity: Effects On Embryo Survival. J. Biol. Chem. 2016 accepted for publication.
- 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.
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