Training In Cardiovascular Physiology &Pharmacology

Summary

Principal Investigator: Kirk U Knowlton
Abstract: DESCRIPTION (provided by applicant): This proposal is for a long-standing, comprehensive, multidisciplinary program to train cardiovascular scientists in mechanisms of disease, and means to develop novel diagnostic and therapeutic approaches to cardiovascular illnesses. It focuses on the use of cellular, molecular, pharmacologic, physiologic and bioengineering approaches. The range of scientific disciplines in the training plan includes: 1) myocyte signaling and cell death, 2) cardiac development and regeneration, 3) the role of the extrasarcomeric cytoskeleton in cardiomyopathy, and 4) cardiac bioengineering. The proposal aims to continue with 2 pre-doctoral and 6 post-doctoral positions each year. The pre-doctoral training positions will draw from some of the best of a group of excellent students in the University of California, San Diego (UCSD) Biomedical Sciences, Bioengineering, and Medical Scientist Training (MSTP) programs. The postdoctoral positions are drawn from a large pool of Ph.D. postdoctoral fellows at UCSD, a Physician-Scientist Training Program (PSTP) in the Department of Medicine, and select cardiology fellows who demonstrate a strong interest in pursuing a career in cardiovascular science. The program aims to groom the trainees in acquisition of the knowledge and skills necessary to become independent investigators in cardiovascular research. At least two years of training will be required of all postdoctoral trainees. The Faculty of the program are from the Departments of Medicine, Pharmacology, Anesthesiology, School of Pharmacy and Bioengineering at UCSD and draw from the resources of the School of Medicine, School of Engineering, the Institute of Engineering in Medicine, the Cardiac Biological Science and Engineering Center, the new Sulpizio Cardiovascular Center, the Skaggs School of Pharmacy and Pharmaceutical Sciences and the Department of Veterans Affairs Medical Center. The program has both didactic and laboratory experiences. Most trainees will be cross-trained in several disciplines. Thoughtful career guidance will be a component of all stages of the program. Importantly, the training program will be tailored to meet each individual's specific long-term goals, to equip them best for a successful future in academic medicine and research. 117 trainees have received support from this training program since its inception in 1978. Almost 50% now hold positions as academic faculty with several serving in or having served in leadership positions. Another 30% have scientific positions in the biotechnology industry. Over the last 10 years, 81% of former trainees have continued to actively publish original work in journals cited by PubMed. This proposal will facilitate the continued pattern of success that has been established over the years. (End of Abstract)
Funding Period: 1979-07-01 - 2018-06-30
more information: NIH RePORT

Top Publications

  1. ncbi Luminescent dipyrrinato complexes of trivalent group 13 metal ions
    Van S Thoi
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093 0358, USA
    Inorg Chem 45:10688-97. 2006
  2. pmc Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with myofibrillar and intermyofibrillar disorganization in mice
    Andrea A Domenighetti
    Department of Medicine, Cardiology Division
    Hum Mol Genet 23:209-25. 2014
  3. pmc Defining the cellular repertoire of GPCRs identifies a profibrotic role for the most highly expressed receptor, protease-activated receptor 1, in cardiac fibroblasts
    Aaron N Snead
    Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA
    FASEB J 26:4540-7. 2012
  4. pmc RhoA protects the mouse heart against ischemia/reperfusion injury
    Sunny Yang Xiang
    Department of Pharmacology, UCSD, San Diego, California 92093 0636, USA
    J Clin Invest 121:3269-76. 2011
  5. pmc Effects of (-)-epicatechin on myocardial infarct size and left ventricular remodeling after permanent coronary occlusion
    Katrina Go Yamazaki
    Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
    J Am Coll Cardiol 55:2869-76. 2010
  6. pmc Enzymatic activation of a matrix metalloproteinase inhibitor
    Jody L Major Jourden
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0358, USA
    Chem Commun (Camb) 46:1241-3. 2010
  7. ncbi Hydrogen-bond rigidified BODIPY dyes
    Jennifer A Jacobsen
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0358, USA
    Dalton Trans 39:957-62. 2010
  8. ncbi To bind zinc or not to bind zinc: an examination of innovative approaches to improved metalloproteinase inhibition
    Jennifer A Jacobsen
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093 0358, USA
    Biochim Biophys Acta 1803:72-94. 2010
  9. pmc Myogenic Akt signaling upregulates the utrophin-glycoprotein complex and promotes sarcolemma stability in muscular dystrophy
    Angela K Peter
    Department of Physiological Science, University of California, Los Angeles, CA 90095, USA
    Hum Mol Genet 18:318-27. 2009
  10. pmc Mechanisms of conduction slowing during myocardial stretch by ventricular volume loading in the rabbit
    Robert W Mills
    Department of Bioengineering, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0412, USA
    Am J Physiol Heart Circ Physiol 295:H1270-H1278. 2008

Detail Information

Publications16

  1. ncbi Luminescent dipyrrinato complexes of trivalent group 13 metal ions
    Van S Thoi
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093 0358, USA
    Inorg Chem 45:10688-97. 2006
    ..The new complexes are important additions to the widely used family of dipyrrin-based fluorescent species and show that dipyrrinato complexes containing metals other than BF2 and zinc(II) may be useful fluorophores...
  2. pmc Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with myofibrillar and intermyofibrillar disorganization in mice
    Andrea A Domenighetti
    Department of Medicine, Cardiology Division
    Hum Mol Genet 23:209-25. 2014
    ..Overall, our data show that loss of FHL1 function leads to myopathy in vivo and suggest that loss of function of FHL1 may be one of the mechanisms underlying muscle dystrophy in patients with FHL1 mutations. ..
  3. pmc Defining the cellular repertoire of GPCRs identifies a profibrotic role for the most highly expressed receptor, protease-activated receptor 1, in cardiac fibroblasts
    Aaron N Snead
    Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA
    FASEB J 26:4540-7. 2012
    ....
  4. pmc RhoA protects the mouse heart against ischemia/reperfusion injury
    Sunny Yang Xiang
    Department of Pharmacology, UCSD, San Diego, California 92093 0636, USA
    J Clin Invest 121:3269-76. 2011
    ..They also reveal unexpected roles for PKD as a downstream mediator of RhoA and in cardioprotection against I/R...
  5. pmc Effects of (-)-epicatechin on myocardial infarct size and left ventricular remodeling after permanent coronary occlusion
    Katrina Go Yamazaki
    Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
    J Am Coll Cardiol 55:2869-76. 2010
    ....
  6. pmc Enzymatic activation of a matrix metalloproteinase inhibitor
    Jody L Major Jourden
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0358, USA
    Chem Commun (Camb) 46:1241-3. 2010
    ..Matrix metalloproteinase inhibitors (MMPi) possessing a glucose protecting group on the zinc-binding group (ZBG) show a dramatic increase in inhibitory activity upon cleavage by beta-glucosidase...
  7. ncbi Hydrogen-bond rigidified BODIPY dyes
    Jennifer A Jacobsen
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0358, USA
    Dalton Trans 39:957-62. 2010
    ..The modular synthesis of these compounds and their robust photophysical properties suggest that they may be useful compounds for materials and biological photochemical applications...
  8. ncbi To bind zinc or not to bind zinc: an examination of innovative approaches to improved metalloproteinase inhibition
    Jennifer A Jacobsen
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093 0358, USA
    Biochim Biophys Acta 1803:72-94. 2010
    ..The studies discussed here bode well for the development of ever more selective, potent, and well-tolerated MMPi for treating several important disease pathologies...
  9. pmc Myogenic Akt signaling upregulates the utrophin-glycoprotein complex and promotes sarcolemma stability in muscular dystrophy
    Angela K Peter
    Department of Physiological Science, University of California, Los Angeles, CA 90095, USA
    Hum Mol Genet 18:318-27. 2009
    ....
  10. pmc Mechanisms of conduction slowing during myocardial stretch by ventricular volume loading in the rabbit
    Robert W Mills
    Department of Bioengineering, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0412, USA
    Am J Physiol Heart Circ Physiol 295:H1270-H1278. 2008
    ....
  11. pmc Short- and long-term effects of (-)-epicatechin on myocardial ischemia-reperfusion injury
    Katrina Go Yamazaki
    Department of Medicine, UCSD Cardiology, 9500 Gilman Dr 0613J, BSB 4028, La Jolla, CA 92093, USA
    Am J Physiol Heart Circ Physiol 295:H761-7. 2008
    ..Results warrant the evaluation of cocoa flavanols as possible therapeutic agents to limit ischemic injury...
  12. ncbi Combined deficiency of dystrophin and beta1 integrin in the cardiac myocyte causes myocardial dysfunction, fibrosis and calcification
    Laila Elsherif
    Department of Medicine, University of California at San Diego School of Medicine, La Jolla, USA
    Circ Res 102:1109-17. 2008
    ....
  13. ncbi Rare examples of transition-metal-main-group metal heterometallic metal-organic frameworks from gallium and indium dipyrrinato complexes and silver salts: synthesis and framework variability
    Jay R Stork
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093 0358, USA
    Inorg Chem 46:11213-23. 2007
    ..All of the dipyrrin compounds reported here have been characterized by single-crystal X-ray crystallography, including the first crystallographically characterized example of a 1,2,3-unsubstituted free-base dipyrrin, 4-pyrdpmH...
  14. pmc The atypical Rho GTPase, RhoU, regulates cell-adhesion molecules during cardiac morphogenesis
    Michael Dickover
    Department of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA 92093 0613J, USA
    Dev Biol 389:182-91. 2014
    ..Failure to properly form these cell adhesions during cardiac development may lead to structural heart defects and mechanistically account for the cellular events that occur in certain human congenital heart diseases. ..