Ronald Li

Ronald Li

Position Title
Associate Professor

Unit
Department of Cell Biology and Human Anatomy, School of Medicine
Institute for Pediatric Regenerative Medicine

Room 650 2425 Stockton Blvd, Sacramento, CA 95817
Bio

Profile Introduction

Human embryonic stem cells (hESCs), isolated from the inner cell mass of human blastocysts, can propagate indefinitely in culture while maintaining their pluripotency, including the ability to differentiate into human heart cells that do not otherwise regenerate once damaged; therefore, hESCs may provide an unlimited ex vivo source of such specialized cells as cardiomyocytes and neurons for transplantation and other cell-based heart therapies. In combination with recent advances in biomedical engineering techniques, hESCs have enabled researchers to pursue the revolutionary paradigm of regenerative medicine for repairing, replacing or enhancing organ function in irreversible diseases (e.g. heart failure, spinal cord injury). Our laboratory has three major areas of interest: 1) stem cell biology; 2) the basis of cellular excitability; 3) structure-function of ion channels. We seek to understand what underlie cellular excitability and various electrical disorders (e.g. arrhythmias), and how the associated electrical defects can be corrected. Our structure-function analysis of ion channels serves as a platform to create a better understanding of the basic biology of these critical signaling proteins. We then apply the knowledge gained from these basic studies to design and create custom-tailored cells and tissues (such as heart, neuronal and insulin-secreting cells from genetically-engineered human embryonic stem cells) for various gene- and cell-based therapies, and to develop tissue-specific drugs and high-throughput biosensors. Several in vitro and in vivo gene transfer and transplantation models are employed to test the functional efficacy of our approaches. Techniques that we commonly employ include electrophysiology, imaging, lentiviral and adenoviral gene transfer, mathematical modeling, computational modeling of 3D protein structure, various protein- and tissue-engineering approaches etc. Overall, our research goal is to better understand the fundamental mechanisms of various human diseases, and to translate experimental concepts into potential therapies.

Research Interests

Human embryonic stem cells (hESCs), isolated from the inner cell mass of human blastocysts, can propagate indefinitely in culture while maintaining their pluripotency, including the ability to differentiate into human heart cells that do not otherwise regenerate once damaged; therefore, hESCs may provide an unlimited ex vivo source of such specialized cells as cardiomyocytes and neurons for transplantation and other cell-based heart therapies. In combination with recent advances in biomedical engineering techniques, hESCs have enabled researchers to pursue the revolutionary paradigm of regenerative medicine for repairing, replacing or enhancing organ function in irreversible diseases (e.g. heart failure, spinal cord injury). Our laboratory has three major areas of interest: 1) stem cell biology; 2) the basis of cellular excitability; 3) structure-function of ion channels. We seek to understand what underlie cellular excitability and various electrical disorders (e.g. arrhythmias), and how the associated electrical defects can be corrected. Our structure-function analysis of ion channels serves as a platform to create a better understanding of the basic biology of these critical signaling proteins. We then apply the knowledge gained from these basic studies to design and create custom-tailored cells and tissues (such as heart, neuronal and insulin-secreting cells from genetically-engineered human embryonic stem cells) for various gene- and cell-based therapies, and to develop tissue-specific drugs and high-throughput biosensors. Several in vitro and in vivo gene transfer and transplantation models are employed to test the functional efficacy of our approaches. Techniques that we commonly employ include electrophysiology, imaging, lentiviral and adenoviral gene transfer, mathematical modeling, computational modeling of 3D protein structure, various protein- and tissue-engineering approaches etc. Overall, our research goal is to better understand the fundamental mechanisms of various human diseases, and to translate experimental concepts into potential therapies.

Honors and Awards

  • BEST BASIC SCIENCE PAPER of 2005 by Circulation, American Heart Association
  • First Prize, Basic Research Faculty Award, Department of Medicine, The Johns Hopkins University, 2004
  • First Prize, Young Investigator Award, North American Society of Pacing and Electrophysiology, 2002.
  • First Prize, Basic Research Junior Faculty Award, Department of Medicine, The Johns Hopkins University, 2002
  • Research Career Development Award, Cardiac Arrhythmias Research and Education Foundation, 2001
  • Top Prize for Basic Research, Young Investigator (Helen B. Taussig) Award, The Johns Hopkins University School of Medicine, 2001
  • First Prize, Basic Research Fellow Award, Department of Medicine, The Johns Hopkins University, 2001
  • American Heart Association Post-doctoral Fellowship Award, 2001 (percentile rank <1%; declined due to faculty promotion)
  • Heart and Stroke Foundation of Canada Post-doctoral Fellowship Award, 1999-2001
  • First Prize, 20th Annual Department of Medicine Residents and Fellows Medical Research Competition, University of Toronto, 1998
  • Ontario Graduate Scholarship, 1997
  • Junior Personnel Research Award, Center for Cardiovascular Research, University of Toronto, 1996
  • Graduation on Dean’s Honor List, 1994
  • Sir William Elson Thermodynamic Scholarship, 1992
  • Faculty of Science Biochemistry Upper Year Scholarship, 1991
  • University of Waterloo Chem13 Award, 1990

    Professional Societies

    • American Heart Association, American Society of Gene Therapy, International Society of Stem Cell Research, Biophysical Society, Cardiac Muscle Society, Institute of Cardiovascular Sciences and

    Degrees

    • 1998 PhD Physiology/Cardiology University of Toronto, Canada
    • 1994 BS Biochemistry/Biotechnology University of Waterloo, Canada

    Publications

    Representative list of recent publications (from 2004 only):

    Tian, Xue, Heecheol, Cho, Fadi Akar, Suk-ying Tsang, Steven Jones, Eduardo Marbán, Gordon F. Tomaselli, Ronald A. Li (2005). Functional integration of electrically-active cardiac derivatives from genetically-engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: Insights into the development of cell-based pacemakers. Circulation. 111(1):11-20. BEST PAPER OF THE YEAR 2005 AWARD.

    Hung-Fat Tse, Chu-Pak Lau, Chung-Wah Siu, Kai Wang, Qing-Yong Zhang, Tian Xue, Ronald A. Li (2006). A bio-artificial sinus node constructed via in vivo gene transfer of an engineered pacemaker (HCN) channel reduces the dependence on electronic pacemaker in a sick sinus syndrome model. Circulation. 114(10):1000-11. See Editorial Comments Change in Pacing Paradigm in the same issue 114(10):986-8.

    Tian Xue, David Chung-Wah Siu, Deborah K. Lieu, Chu-Pak Lau, Hung-Fat Tse, Ronald A. Li (2007). Mechanistic role of If revealed by induction of ventricular automaticity by somatic gene transfer of gating-engineered pacemaker (HCN) channels. Circulation. 115(14):1839-50

    George Wang, Tian Xue, Suk-ying Tsang, Johnny Wong, Linzhao Cheng, Janet Zhang, Guirong Li, Chu-Pak Lau, Hung-Fat Tse, Ronald A. Li. (2005) Electrophysiological properties of pluripotent human and mouse embryonic stem cells. Stem Cells. 23(10):1526-34.

    Jennifer C. Moore, Linda W. van Laake, Stefan R. Braahm, Tian Xue, Suk-Ying Tsang, Dorien Ward, Robert Passier, Leon L. Tertoolen, Ronald A. Li, and Christine L. Mummery. 2005. Human Embryonic Stem Cells: Genetic Manipulation on the Way to Cardiac Cell Therapies. Reproductive Toxicology. 20(3):377-91.

    Ronald A. Li, Jennifer Moore, Yelena Tarasova, Kenneth R. Boheler (2006). Human Embryonic Stem Cell-Derived Cardiomyocytes: Therapeutic Potentials and Limitations. Journal of Stem Cells. 1(2):109.

    Suk-ying Tsang, Jennifer C. Moore, Rika van Huizen, Camie W. Chan, Ronald A. Li (2007). Ectopic expression of systemic RNA interference defective protein (SID-1) in embryonic stem cells. Biochem Bioph Res Co. 357(2):480-6

    David Chung-Wah Siu, Deborah K. Lieu, Ronald A. Li (2007). HCN-encoded Pacemaker Channels: From Physiology, Biophysics to Bioengineering. J. Mem. Biol. In press.

    David Chung-Wah Siu, Jennifer Moore, Ronald A. Li (2007). Human Embryonic Stem Cell-Derived Cardiomyocytes as a Potential Solution to Heart Diseases. Cardiovascular & Hematological Disorders - Drug Targets. In press.

    Wasim El-kholy, Tian Xue, Jingyu Diao, Catherine B. Chan, Xiaolin Wang, Patrick E. MacDonald, Ronald A. Li, Robert G. Tsushima, Michael B. Wheeler (2007). Hyperpolarization-activated currents in pancreatic ? cells modulate insulin secretion . Mol. Endocrinology. 21(3):753-64.

    Wei Xiong, Ronald A. Li and Gordon F. Tomaselli. (2006). A conserved ring of charge in mammalian Na+ channels: a molecular regulator of the outer pore conformation during slow inactivation. J. Physiol. 2006 576:739-54.

    Ezana Azene, Tan Xue, Gordon F. Tomaselli, Ronald A. Li (2005). Hysteretic current-voltage behavior of HCN-encoded pacemaker channels: Insights into the physiological role of If in cardiac pacing. Cardiovas. Res. 67(2): 263-73.

    Suk-ying Tsang, Robert G. Tsushima, Gordon F. Tomaselli, Ronald A. Li, Peter H. Backx (2005) A multi-functional aromatic residue in the external pore vestibule of Na+ Channels contributes to the local anesthetic receptor. Mol. Pharm. 67(2):424-434.

    Roselle Abraham, Charles Henrikson, Leslie Tung, Miguel Aon, Tian Xue, Ronald A. Li, Brian O'Rourke, Eduardo Marban. (2005). Anti-arrhythmic engineering of skeletal muscle myoblasts for cardiac transplantation. Circ. Res. 97(2): 159-67.

    Tian, Xue, Ronald A. Li (2005). Circulation. 112(6):e82-83.

    Ezana Azene, Eduardo Marban, Gordon F. Tomaselli, Ronald A. Li (2005). Non-equilibrium behavior of HCN channels: Insights into the role of HCN channels in native and engineered pacemakers. Cardiovas. Res. 67(2): 263-73.

    Ronald A. Li (2004) Probing the sodium channel pore structure with the deadly µ-conotoxin. Toxicon. 44(2):117-22.

    Heinte Lesso, Suk-ying Tsang, Ronald A. Li (2004). Critical intra-linker interactions of HCN channels revealed by systematic interchange of S3-S4 determinants. Biochem Biophy Res Co. 322(2) 652-658.

    Suk-ying Tsang, Heinte Lesso, Ronald A. Li (2004). Dissecting the structural and functional roles of the S3-S4 linker of pacemaker (HCN) channels by systematic length alterations. J. Biol. Chem. 279:43752-9.

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