University of Wisconsin–Madison

Timothy Kamp, MD, PhD, FACC

Professor, Department of Medicine (Cardiology)

tjk@medicine.wisc.edu

608-263-1172

8459 Wisconsin Institute for Medical Research
1111 Highland Avenue

Timothy Kamp

Research Interests

Cardiovascular Calcium Channels Function, Structure and Regulation. Cardiac Ca2+ channels play an important role in cellular excitability by allowing the rapid influx of Ca which depolarizes the cell. The resulting increase in intracellular [Ca2+] is essential for regulation of Ca2+-dependent processes including excitation-contraction coupling, excitation- secretion coupling, and gene regulation. Current research focuses on defining the exact subunit composition of the channel in the heart and determining the molecular mechanisms of regulation of this channel complex. A variety of molecular biology, cellular electrophysiology, biochemical, and pharmacological approaches are employed in these studies which are currently evaluating the role of PKA and PKC pathways regulating the channel. Several lines of conditional knockout mice have been generated to facilitate these studies.

Remodeling of Cardiomyocytes and Excitation-Contraction Coupling in Heart Failure. In congestive heart failure there are fundamental abnormalities in excitation-contraction coupling at the cellular level which remain poorly understood. We have recently demonstrated a striking depletion of the T-tubule network in failing myocytes using confocal microscopy. As T-tubules are normally the major site of excitation-contraction coupling in ventricular myocytes, this remodeling of failing myocytes has important functional impact. Ongoing studies are exploring the changes in membrane proteins associated with this cellular remodeling and the effect on excitation-contraction coupling using a variety of animal models and tissue from explanted human hearts.

Isolation and Characterization of Human Embryonic Stem Cell-Derived Cardiomyocytes. Embryonic stem (ES) cells are pluripotent cells capable of developing into specific cell types of all three germ layers including cardiomyocytes. The last ten years have seen extensive efforts to characterize in vitro murine ES cell-derived cardiomyocytes; however, little is known about the ability of human ES cells to differentiate into cardiomyocytes. Our initial work with human ES cells has demonstrated that these cells can form spontaneously contracting embryoid bodies. Therefore, human ES cells can form cardiomyocytes, but the process of differentiation and the properties of those cardiomyocytes will have important differences with the murine ES-derived cardiomyocytes. The purpose of the present research is to optimize the differentiation of human ES cells into cardiomyocytes and to characterize the resulting cardiomyocytes. Ultimately, these cells will have tremendous potential for cell-based therapies for a variety of heart diseases. In addition, they will provide a useful cell culture model for a variety of basic research studies.

Other Positions & Affiliations

  • Co-Associate Director and Trainer, MD/Ph.D. Training Program
  • Editorial Board Member, Circulation Research
  • Editorial Board Member, Stem Cells

Selected Publications

(Find publications on PubMed)

  • Boczek NJ, Best JM, Tester DJ, Giudicessi JR, Middha S, Evans JM, Kamp TJ, and Ackerman MJ (2013) . Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long QT syndrome. Circ Cardiovasc Genet. [Epub ahead of print]
  • Lian X, Zhang J, Azarin SM, Zhu K, Hazeltine LB, Bao X, Hsiao C, Kamp TJ, and Palecek SP (2013). Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions. Nat Protoc. 8:162-75. PMID: 23257984
  • Lian X, Zhang J, Zhu K, Kamp TJ, and Palecek SP (2012). Insulin Inhibits Cardiac Mesoderm, not Mesendoderm, formation during Cardiac Differentiation of Human Pluripotent Stem Cells and Modulation of Canonical Wnt Signaling Can Rescue this Inhibition. Stem Cells. 31:447-457. [Epub ahead of print] PMID: 23193013
  • Best JM and Kamp TJ (2012). Different subcellular populations of L-type Ca(2+) channels exhibit unique regulation and functional roles in cardiomyocytes. J Mol Cell Cardiol. 52:376-87. PMID: 21888911
  • Kamp TJ (2011). An electrifying iPSC disease model: long QT syndrome type 2 and heart cells in a dish. Cell Stem Cell. 8:130-1. PMID: 21295269
  • Su X, Young EW, Underkofler HA, Kamp TJ, January CT, and Beebe DJ (2011). Microfluidic cell culture and its application in high-throughput drug screening: cardiotoxicity assay for hERG channels. J Biomol Screen. 16:101-11. PMID: 21131594
  • Buschke DG, Squirrell JM, Ansari H, Smith MA, Rueden CT, Williams JC, Lyons GE, Kamp TJ, Eliceiri KW, and Ogle BM (2010). Multiphoton flow cytometry to assess intrinsic and extrinsic fluorescence in cellular aggregates: applications to stem cells. Microsc Microanal. 17:540-54. PMID: 20684798
  • Mohr JC, Zhang J, Azarin SM, Soerens AG, de Pablo JJ, Thomson JA, Lyons GE, Palecek SP, and Kamp TJ (2009). The microwell control of embryoid body size in order to regulate cardiac differentiation of human embryonic stem cells. Biomaterials. 31:1885-93. PMID: 19945747
  • Zhang J, Wilson GF, Soerens AG, Koonce CH, Yu J, Palecek SP, Thomson JA, and Kamp TJ (2009). Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res. 104:e30-41. PMID: 19213953
  • Raval AN, Kamp TJ, and Hogle LF (2008). Cellular therapies for heart disease: unveiling the ethical and public policy challenges. J Mol Cell Cardiol. 45:593-601. PMID: 18155721
  • Meethal SV, Potter KT, Redon D, Munoz-Del-Rio A, Kamp TJ, Valdivia HH, and Haworth RA (2007). Structure-function relationships of Ca spark activity in normal and failing cardiac myocytes as revealed by flash photography. Cell Calcium. 41:123-134. PDF PMID 16837043
  • Kamp TJ and Chiamvimonvat N (2006). Mission impossible: IGF-1 and PTEN specifically “Akt”ing on cardiac L-type Ca2+ channels. Circ Res. 98:1349-1351. PDF PMID 16763171
  • Singla DK, Hacker TA, Ma L, Douglas PS, Sullivan R, Lyons GE, and Kamp TJ(2006). Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types. J Mol Cell Cardiol. 40:195-200. PDF PMID 16288779
  • Kumar D, Kamp TJ, and LeWinter MM (2005). Embryonic stem cells: differentiation into cardiomyocytes and potential for heart repair and regeneration. Coron Artery Dis.16:111-116. PDF PMID 15735404
  • Cohen RM, Foell JD, Balijepalli RC, Shah V, Hell JW, and Kamp TJ (2005).Unique modulation of L-type Ca2+ channels by short auxiliary beta1d subunit present in cardiac muscle. Am J Physiol Heart Circ Physiol. 288:H2363-2374. PDF PMID 15615847
  • Lokuta AJ, Maertz NA, Meethal SV, Potter KT, Kamp TJ, Valdivia HH, and Haworth RA (2005). Increased nitration of the sarcoplasmic reticulum Ca2+ ATPase in human heart failure. Circulation. 111:988-995. PDF PMID 15710754
  • Kumar D, Hacker TA, Buck J, Whitesell LS, Kaji EH, Douglas PS, and Kamp TJ(2005). Distinct mouse coronary anatomy and myocardial infarction consequent to ligation. Coron Artery Dis. 16:41-44. PDF PMID 15654199
  • Chun W, Grist TM, Kamp TJ, Warner TF, and Christian TF (2004). Infiltrative eosinophilic myocarditis diagnosed and localized by cardiac magnetic resonance imaging. Circulation. 110:e19. PDF PMID 15262855
  • Foell JD, Balijepalli RC, Delisle BP, Yunker AMR, Robia SL, Walker JW, McEnery MW, January CT, and Kamp TJ (2004). Molecular heterogeneity of calcium channel b subunits in canine and human heart: Evidence for differential subcellular localization. Physiol Genomics. 17:183-200. PDF PMID 14762176
  • Robu VG, Pfeiffer ES, Robia SL, Balijepalli RC, Pi Y, Kamp TJ, and Walker JW (2003). Localization of functional endothelin receptor signaling complexes in cardiac transverse tubules. J Biol Chem. 278:48154-48156. PDF PMID 12972433