Profile: Ke-He Ruan

Ke-He Ruan
Ke-He Ruan, M.D., Ph.D.
Professor of Medicinal Chemistry & Pharmacology
Director, Center for Experimental Therapeutics and Pharmacoinformatics (CETP)

Department of Pharmacological and Pharmaceutical Sciences
552 Science and Research Building 2
Houston, TX 77204-5037
713-743-1771
713-743-1229 (fax)
khruan@uh.edu

Education

M.D. in Medicine, Fujian Medical University
Ph.D. in Biomedical Science, Biochemistry, Medical College of Miyazaki
Post-doctoral Fellowship in Biochemistry, Baylor College of Medicine

Research Interests

  • Signaling Molecules and Drugs: Eicosanoids, Non-steroidal anti-inflammatory drugs (NSAIDs), targeting eicosanoid-biosynthesizing drugs, targeting eicosanoid-signaling drugs.
  • Therapeutics Development for Diseases: Using small compounds/peptide/protein/gene/cells to develop novel approaches targeting Vascular Diseases (such as stroke and heart diseases), cancers and tissue regenerations.
  • Drug targets: G Protein coupling receptors, P450 enzymes, eicosanoid-synthesizing enzymes, eicosanoid receptors
  • Molecular Mechanisms: Eicosanoid Biosynthesis and Signaling in thrombosis, ischemia, cancers and stem cells.
  • Biomedical field: Protein engineering, peptide synthesis, drug designs, membrane proteins, NMR structural biology.
  • Approaches: Molecular cloning, protein/cell engineering, cell engineering, animal models, NMR spectroscopy, high throughput screening, virtual screening, computational chemistry.
  • Assay Development: Automation robotic system for High throughput drug screening, virtual drug designs and screening, integration of experimental and virtual approaches in drug designs and screening.

Patents

  • Compositions and Methods of Use for a Protein that Converts Arachidonic Acid into Prostacyclin, 2006.
  • Provisional patent: Engineering of a Single Protein with Triple Catalytic Enzyme Activities Directly Converted Arachidonic Acid into Prostaglandin E2, 2006.

Courses: University of Houston

  • PHAR5302 Medicinal Chemistry
  • PCOL7333 Molecular Pharmacology
  • PHAR5289 Herbal Medicine Drug Design
  • PHAR5389 Herbal Medicine Research

Courses: UT Graduate School of Biomedical Science at Houston

  • GS040022 Vascular Biology: Basic Science to Clinical Research
  • GS040042 Stem Cells in Biomedicine

Affiliations

  • Director, Center of Experimental Therapeutics and Pharmacoinformatics (CETP), University of Houston
  • Adjunct Professor, University of Texas Graduate School at Houston
  • Adjunct Professor, Fujian Medical University
  • Faculty Member of Texas Heart Institute
  • Member of Houston Area Molecular Biophysics Program (HAMBP)
  • Advisory Committee Member of NMR Structural Biology Center in University Houston
  • Member of Gulf Coast Consortium in Magnetic Resonance (MGCCMR)
  • Member of American Chemistry Society (ACS)
  • Member of American Society for Biochemistry and Molecular Biology (ASBMB)
  • Member of American Protein Society
  • Member of Society of Chinese Biosciences in America

Editorial Board Positions

  • 2011 – present: Editor-in-Chief of British Journal of Pharmaceutical Research
  • 2007 – present: Associate Editor of the African Journal of Pharmacy and Pharmacology (AJPP)
  • 2006 – present: Editorial Board member for “Recent Patents on CNS Drug Discovery” Journal (Bentham Science Publishers)
  • 2004 – present: Editorial Board member for BMC Biochemistry
  • Co-Guest Editor for Current Pharmaceutics Design (impact factor: 5.0, in 2004) for a special issue of the hot topic "Latest Developments in Pharmaceutical Design of Arachidonic Acid Metabolites: Prostaglandins, Thromboxanes, Hepoxilins and Isoprostanes"
  • 2003 – present: Editorial Board member for Spectroscopy Journal (An International Biomedical Journal. Editor, Partic Haris, England)
  • 2002 – present: Member of International Reviewers Panel for Medical Science Monitor Journal (An international medical journal for experimental and clinic research, Editor, Mark R. Graczynski)

Activity as a Journal Reviewer

  • Journal Biological Chemistry (J.B.C., U.S.A.)
  • Biochemical Pharmacology Journal (U.S.A.)
  • Trends in Pharmacological Sciences (TIPS, U.S.A.)
  • Life Sciences (U.S.A.)
  • Archives of Biochemistry and Biophysics (U.S.A.)
  • Carcinogenesis (U.S.A.)
  • Journal of Medicinal Chemistry (American Chemical Society Journal)
  • Journal of Pharmacology and Experimental Therapeutics (American Society for Pharmacology and Experimental Therapeutics [ASPET] Journal)
  • Cancer Investigation

Service on Grant Review Panels, Study Sections, Committees

  • NIH, NIDDK Special emphasis review panel member
  • NIH, NHLB Special emphasis review panel member
  • American Heart Association Grant Review Panel
  • UH GEAR review panel
  • Reviewer for grant peer review committee of National Health Research Institutes, Taiwan, Republic China (2001)
  • Grant reviewer for the Research Grants Council (RGC) of Hong Kong (2007)
  • Grant Review Committee Member of Fujian Medical University, P.R. China (2004)

Honors, Awards, & Grants

  • News feature by American Chemical Society News Press on Nov. 27, 2006, Engineering the "Super Enzyme" -- a potential new weapon against heart disease’.
  • News feature by Worldjournal.com on Nov. 29, 2006 for Innovative Engineering of a “Super Enzyme”.
  • News Feature by University of Texas Health Science center at Houston News Room “Super Enzyme and Potential heart treatment emerge from Vioxx Research”
  • News Feature by Science Daily, Nov 28 2006, ‘Engineering The 'Super Enzyme' -- A Potential New Weapon Against Heart Disease’
  • News Feature by FirstScience.com, Nov 22 2006, ‘Engineering the "Super Enzyme" -- a potential new weapon against heart disease’
  • News Feature by Mooshee.com, , ‘Engineering the "Super Enzyme" -- a potential new weapon against heart disease’
  • News Feature by Spectroscopy.com, ‘Assembled Receptor Spectra’
  • News Feature by NMR Knowledge Base, ‘Assembled Receptor Spectra’
  • National Institute of Health RO1 supplement Award, 2006.
  • Interviewed by Sciencebase.com (Cambridge UK) and featured by NMR Base Knowledge News in recognition of the major findings of the structure/function relationship studies for prostanoid receptor in July, 2004.
  • National Institute of Health RO1 Award, Dec. 2004.
  • National Institute of Health RO1 Award, NIH, Aug. 2004.
  • National Institute of Health RO1 Award, NIH, 2000.
  • National Institute of Health PPG project Award, 2000.
  • National Institute of Health FIRST AWARD (R29), 1996.
  • Honor from American Heart Association, Texas Affiliate: Certificate of Appreciation for dedicated service in advancing the fight against Heart disease and stroke from American Heart Association, Texas Affiliate, 1996.
  • Grant-in-aid, American Heart Association Award, Texas Affiliate, 1995.
  • Grant-in-aid, American Heart Association Award, Texas Affiliate, 1993.
  • The First National Young Scientist Award from National Science and Technology Commission, P.R. of China, 1989.
  • Interviewed and Featured by Japanese NHK TV station, and 5 major news papers between Feb. - March 1986 as an outstanding scientist in developing the breaking record sensitive method measuring hormone insulin.
  • Interviewed and Featured by Chinese central TV station, Radio station and Multiple Chinese News papers, between 1986 and 1988, as an ‘outstanding young scientist in biomedical sciences’.
  • Award (First place) of Science and Technology Development from Fujian Province Science and Technology Commission, P.R. China, 1987.
  • Award (First place) of Medical Science from Fujian Province Medical
    Council, P.R of China, 1987.
  • Governor Award of Fujian Province, P.R. of China, 1986.

Publications

Refereed Journal Articles (since 2006)

Zhou L, Chen Z, Vanderslice P, So SP, Ruan KH, Willerson JT, Dixon RA. Endothelial-Like Progenitor Cells Engineered to Produce Prostacyclin Rescue Monocrotaline-Induced Pulmonary Arterial Hypertension and Provide Right Ventricle Benefits. Circulation. 2013 Jul 10. [Epub ahead of print]

Ruan KH, Mohite AJ, So SP. Resistant to thrombosis, induced stroke and heart arrest by incorporation of a single gene of PGI2-synthesizing COX-1-PGIS in vivo: Implication against human heart disease. Int J Cardiol. 2013 Apr 18. doi:pii: S0167-5273(13)00545-7. 10.1016/j.ijcard.2013.03.114. [Epub ahead of print] 

Lin H, Yuan J, Ruan KH, Yang W, Zhang J, Dai Y, Wang R. COX-2-10aa-PGIS Gene Therapy Improves Erectile Function in Rats after Cavernous Nerve Injury. J Sex Med. 2013 Jun;10(6):1476-87. doi: 10.1111/jsm.12147. 

Liu Q, Xi Y, Terry T, So SP, Mohite A, Zhang J, Wu G, Liu X, Cheng J, Ruan KH, Willerson JT, Dixon RA. Engineered endothelial progenitor cells that overexpress prostacyclin protect vascular cells. J Cell Physiol. 2012 Jul;227(7):2907-16. doi: 10.1002/jcp.23035.

Chen Y, Fujita T, Zhang D, Doan H, Pinkaew D, Liu Z, Wu J, Koide Y, Chiu A, Lin CC, Chang JY, Ruan KH, Fujise K. Physical and functional antagonism between tumor suppressor protein p53 and fortilin, an anti-apoptotic protein. J Biol Chem. 2011 Sep 16;286(37):32575-85. Epub 2011 Jul 27.

Ruan KH, Mohite A, So SP, Ruan CH. Establishing novel prostacyclin-synthesizing cells with therapeutic potential against heart diseases. Int J Cardiol. 2011 Jun 29.

Mohite A, Chillar A, So SP, Cervantes V, Ruan KH. Novel mechanism of the vascular protector prostacyclin: regulating microRNA expression. Biochemistry. 2011 Mar 15;50(10):1691-9.

Chillar AJ, Karimi P, Tang K, Ruan KH. An agonist sensitive, quick and simple cell-based signaling assay for determination of ligands mimicking prostaglandin E2 or E1 activity through subtype EP1 receptor: Suitable for high throughput screening. BMC Complement Altern Med. 2011 Feb 7;11:11.

Ruan KH, Cervantes V, So SP. Engineering of a novel hybrid enzyme: an anti-inflammatory drug target with triple catalytic activities directly converting arachidonic acid into the inflammatory prostaglandin E2. Protein Eng Des Sel. 2009 Dec;22(12):733-40.

Ruan KH, Wijaya C, Cervantes V, Wu J. Characterization of the prostaglandin H2 mimic: binding to the purified human thromboxane A2 receptor in solution. Arch Biochem Biophys. 2008 Sep 15;477(2):396-403.

Ruan KH, So SP, Wu H, Cervantes V. Large-scale expression, purification, and characterization of an engineered prostacyclin-synthesizing enzyme with therapeutic potential. Arch Biochem Biophys. 2008 Dec 1;480(1):41-50.

Ni F, So SP, Cervantes V, Ruan KH. A profile of the residues in the second extracellular loop that are critical for ligand recognition of human prostacyclin receptor. FEBS J. 2008;275(1):128-137.

Wu J, Feng M, Ruan KH. Assembling NMR structures for the intracellular loops of the human thromboxane A2 receptor: Implication of the G protein-coupling pocket. Arch Biochem Biophys. 2008;470(1):73-82.

Ruan KH, Wu J, Cervantes V. Characterization of the Substrate Mimic Bound to Engineered Prostacyclin Synthase in Solution Using High-Resolution NMR Spectroscopy and Mutagenesis: Implication of the Molecular Mechanism in Biosynthesis of Prostacyclin. Biochemistry. 2008 Biochemistry. 47(2):680-688.

Ruan KH, Deng H, So SP. Engineering of a protein with cyclooxygenase and prostacyclin synthase activities that converts arachidonic acid to prostacyclin. Biochemistry. 2006 45(47):14003-14011.

Zhang L, Bastepe M, Juppner H, Ruan KH. Characterization of the molecular mechanisms of the coupling between intracellular loops of prostacyclin receptor with the C-terminal domain of the Galphas protein in human coronary artery smooth muscle cells. Arch Biochem Biophys. Jul 25, 2006.

Zhang, L., Wu, J., Ruan KH. Solution structure of the first intracellular loop of prostacyclin receptor and implication of its interaction with the C-terminal segment of G alpha S protein. Biochemistry 45, 1734-1744, 2006.

Dogne JM, Ruan KH. Latest developments in pharmaceutical design of arachidonic acid metabolites: prostaglandsin, thromboxanes, hepoxillins and isoprostanes. Curr Pharm Des. 12, 893, 2006.

Huang, JC, Ruan, CH, Tang, K and Ruan, KH. Prunella stica inhibits the proliferation but not the prostaglandin production of Ishikawa cells. Life Sci. 79, 436-441, 2006.

Ruan, K.-H. and Dogné, J. Implications of the molecular basis of prostacyclin biosynthesis and signaling in pharmaceutical designs. Curr Pharm Design, 12, 925-941, 2006

Dogné, J., Hanson, J., Leval, X., Pratico, D., Pace-Asciak, C., Pirotte, B and Ruan, K.-H. From the design to the clinical application of thromboxane modulators. Curr Pharm Design, 12, 903-923, 2006.

Book Chapters

Ruan, K.-H. Thrombogenesis and anti-thrombogenesis in atherosclerosis mediated by prostanoids through the cyclooxygenase pathway. Chapter V, in: Current Topics in Atherosclerosis Research. Editor Y.J. Geng, Nova Science Publishers Inc. New York, 2005.

Established Collaborations

James T. Willerson, M.D., President and Medical Director, Director of Cardiology Research, and Co-director of the Cullen Cardiovascular Research Laboratories at Texas Heart Institute (THI); Professor of Medicine; former Circulation editor; cardiologist; working on developing gene and cell therapeutics on stroke model using our Super Enzyme.

Yong-Jian Geng, M.D., Ph.D., Professor of Medicine, UTHSC-H and THI. Working on understanding of stem cell signaling for developing a center grant of human stem cell researches and therapeutics.

Ken Fujise, M.D., Professor of Medicine and Chief Cardiologist at UT Medical Branch-Galveston; working on protein structure/function characterization for atherosclerosis.

Run Wang, M.D., Associate Professor, surgeon, urologist; working on the effects of our Super Enzyme on male sex organs.

Joan-Cheng Huang, M.D., Associate Professor of OB/GYN, UTHSC-H; working on Eicosanoid biosynthesis and signaling in reproductive systems.

Peiying Yang, Ph.D., Assistant Professor, Department of Experimental Therapeutics at M.D. Anderson Cancer Center; working on Eicosanoid in cancers.

Zhang-Zhian Zhang, M.D., Ph.D., Associate Professor, University of Hong Kong, Hong Kong; working on natural product drug screening.

JM Dogné, Associate Professor, Natural and Synthetic Drug Research Center, and Medicinal Chemistry, University of Liège, Belgium; working on thrombosis project.

Aimin Huang, M.D., Dean of College of Basic Sciences, Fujian Medical University, P.R. China. Dr. Huang was trained by Dr. Ruan, and now is working on a collaborative project.