Profile: Bradley McConnell

Bradley McConnell
Bradley K. McConnell, Ph.D., FAHA
Associate Professor of Pharmacology
Department of Pharmacological and Pharmaceutical Sciences
460 Science and Research Building 2
713-743-1218 (Voice)
713-743-1232 (Fax)
bkmcconn@central.uh.edu

Education

B.S. (Biology); Pennsylvania State University, University Park, PA

Ph.D. (Physiology and Biophysics); Case Western Reserve University, Cleveland, OH

Postdoctoral Fellow (Genetics); Harvard Medical School, Boston, MA

Research Interests

Heart disease is the No. 1 cause of death in the U.S., affecting more than 12 million Americans. Furthermore, nearly 5 million patients in the U.S. have heart failure; where the heart is unable to efficiently pump blood. Research interests in my laboratory focuses on the genetics and physiology of heart disease, as it relates to normal healthy hearts and to diseased hearts. In particular, our goals are to define mechanisms and to investigate strategies to improve cardiac function in heart disease.

Current research programs in my laboratory include a National Institute of Health (NIH) funded project, focused on targeted disruption of beta-adrenergic signaling to alter cardiac contractility, using transgenic murine models and viral gene transfer.

In this project, we hope to better understand the signal transduction pathways (i.e. cell communication) involved in normal healthy hearts and diseased hearts. In particular, we will characterized the role on one such component of the signal transduction pathway in heart cells; the role of A-Kinase Anchoring Proteins (or simply AKAPs) that are found within the Protein Kinase A (PKA) signaling pathway. The PKA signaling pathway is commonly known to be activated by the binding of epinephrine (adrenaline) to beta-adrenergic receptors on the surface of the heart cell. By using novel genetic approaches to study AKAPs’ role as a central and multi-component regulator of PKA signaling, our studies will yield important insights into the relationship between AKAP function, cardiac muscle signal transduction and heart disease.

Other projects in the laboratory include the identification and characterization of human polymorphisms (DNA variants) that are associated with heart disease; that are found within components of the beta-adrenergic signaling pathway. These investigations will enable us to address many exciting questions in cardiovascular science, in order to fuel efforts for scientific discoveries: for the translation of basic science discoveries to clinical application and for the translation of clinically based discoveries to support basic science research.

Courses

Undergraduate Classes:

    PHPS 3300: Human Physiology and Pathophysiology I

    PHPS 3400: Human Physiology and Pathophysiology II

      PHPS 4401: Pharmacology I

      PHPS 4400: Pharmacology II

      Graduate Classes (PhD):

      PCOL 7350: Cellular Pharmacology

      PCOL 6462: Cardiovascular and Renal Physiology

      Professional Classes (PharmD):

      PHAR 4400: Cellular Life Sciences I (Medical Biochemisty)

        PHAR 4421: Organ Systems Life Sciences II (Physiology)

        PHAR 4251: Skills Lab for Organ Systems Life Sciences II (Physiology Skills Lab)

        PHAR 5397: Cardiac Contractility and Molecular Signaling (Special Topics Course)

Affiliations

  • American Heart Association (AHA)
  • Basic Cardiovascular Science (BCVS) Council of the AHA
  • Biophysical Society
  • American Physiological Society (APS)
  • American Society for Biochemistry and Molecular Biology (ASBMB)
  • American Association of Colleges of Pharmacy (AACP)

Selected Publications

Guillory AN, Yin X, Wijaya CS, Diaz Diaz AC, Rababa'h A, Singh S, Atrooz F, Sadayappan S, McConnell BK. Enhanced Cardiac Function in Gravin Mutant Mice Involves Alterations in the β-Adrenergic Receptor Signaling Cascade. PLoS One. 2013 Sep 18;8(9):e74784. doi: 10.1371/journal.pone.0074784. PMID: 24058627

Rababa'h A, Craft JW Jr, Wijaya CS, Atrooz F, Fan Q, Singh S, Guillory AN, Katsonis P, Lichtarge O, McConnell BK. Protein Kinase A and Phosphodiesterase-4D3 Binding to Coding Polymorphisms of Cardiac Muscle Anchoring Protein (mAKAP). J Mol Biol. 2013 Sep 23;425(18):3277-88. doi: 10.1016/j.jmb.2013.06.014. Epub 2013 Jun 25.

Nguyen VT, Wu Y, Guillory AN, McConnell BK, Fujise K, Huang MH. Delta-opioid augments cardiac contraction through β-adrenergic and CGRP-receptor co-signaling. Peptides. 2012 Jan;33(1):77-82. Epub 2011 Nov 15.

Huang MH, Wu Y, Nguyen V, Rastogi S, McConnell BK, Wijaya C, Uretsky BF, Poh KK, Tan HC, Fujise K. Heart protection by combination therapy with esmolol and milrinone at late-ischemia and early reperfusion. Cardiovasc Drugs Ther. 2011 Jun;25(3):223-32.

Wu Y, Yin X, Wijaya C, Huang MH, McConnell BK. Acute myocardial infarction in rats. J Vis Exp. 2011 Feb 16;(48). pii: 2464. doi: 10.3791/2464

McConnell BK, Popovic Z, Mal N, Lee K, Bautista J, Forudi F, Schwartzman R, Jin JP, Penn M, Bond M. Disruption of protein kinase A interaction with A-kinase-anchoring proteins in the heart in vivo: effects on cardiac contractility, protein kinase A phosphorylation, and troponin I proteolysis. J Biol Chem. 2009 Jan 16;284(3):1583-92. Epub 2008 Oct 21.

Palmer BM, McConnell BK, Li GH, Seidman CE, Seidman JG, Irving TC, Alpert NR, Maughan DW. Reduced cross-bridge dependent stiffness of skinned myocardium from mice lacking cardiac myosin binding protein-C. Mol Cell Biochem. 2004 Aug;263(1-2):73-80.

Song Q, Schmidt AG, Hahn HS, Carr AN, Frank B, Pater L, Gerst M, Young K, Hoit BD, McConnell BK, Haghighi K, Seidman CE, Seidman JG, Dorn GW 2nd, Kranias EG. Rescue of cardiomyocyte dysfunction by phospholamban ablation does not prevent ventricular failure in genetic hypertrophy. J Clin Invest. 2003 Mar;111(6):859-67.

Semsarian C, Ahmad I, Giewat M, Georgakopoulos D, Schmitt JP, McConnell BK, Reiken S, Mende U, Marks AR, Kass DA, Seidman CE, Seidman JG. The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model. J Clin Invest. 2002 Apr;109(8):1013-20.

Berul CI, McConnell BK, Wakimoto H, Moskowitz IP, Maguire CT, Semsarian C, Vargas MM, Gehrmann J, Seidman CE, Seidman JG. Ventricular arrhythmia vulnerability in cardiomyopathic mice with homozygous mutant Myosin-binding protein C gene. Circulation. 2001 Nov 27;104(22):2734-9.

Sprung J, Ogletree-Hughes ML, McConnell BK, Zakhary DR, Smolsky SM, Moravec CS. The effects of propofol on the contractility of failing and nonfailing human heart muscles. Anesth Analg. 2001 Sep;93(3):550-9.

McConnell BK, Fatkin D, Semsarian C, Jones KA, Georgakopoulos D, Maguire CT, Healey MJ, Mudd JO, Moskowitz IP, Conner DA, Giewat M, Wakimoto H, Berul CI, Schoen FJ, Kass DA, Seidman CE, Seidman JG. Comparison of two murine models of familial hypertrophic cardiomyopathy. Circ Res. 2001 Mar 2;88(4):383-9.

Fatkin D, McConnell BK, Mudd JO, Semsarian C, Moskowitz IG, Schoen FJ, Giewat M, Seidman CE, Seidman JG. An abnormal Ca(2+) response in mutant sarcomere protein-mediated familial hypertrophic cardiomyopathy. J Clin Invest. 2000 Dec;106(11):1351-9.

Abstracts and Presentations

Published Abstracts

Bikram, M., Nounou, M.I., Li, D., Silva, G.V, and McConnell, B.K. Development of Non-Viral Gene Delivery Carriers for Ischemic Heart Disease (IHD). Abstract#:10-A-1855-BPS; Biophysical Society 54th Annual Meeting, February 20-24, 2010; San Francisco, CA

Chung, S.Y., Nounou, M.I., Pham, K.A., McConnell, B.K., and Bikram, M. Novel Bioreducible Polymeric Gene Delivery System for Ischemic Heart Disease. Summer Undergraduate Research Day, University of Houston, Houston, TX; October 1, 2009

Avery, A., Wijaya, C., Diaz, A., Guillory, A., McConnell, B.K. Cardiac Signaling: Targeted Disruption of Gravin (AKAP12). Rice-Houston Alliance for Graduate Education and the Professoriate (AGEP) Symposium, Houston, TX; August 6, 2009

McConnell, B.K., Mal, N., Forudi, F., Bautista, J., Jin, J-P., Popovic, Z., Penn, M., and Bond, M. Effect of Targeted Disruption of PKA and AKAP Interaction on Cardiac Contractility, PKA Phosphorylation, and TnI proteolysis in Rat Hearts in vivo. Cardiac and Vascular Cell Biology Second Annual Mini-Retreat, March 30, 2007

McConnell, B.K., Mal, N., Forudi, F., Bautista, J., Jin, J-P., Popovic, Z., Penn, M., and Bond, M. Targeted Disruption of PKA and AKAP Interaction on Cardiac Contractility in Rat Hearts in vivo. 16th Annual Perspectives in Biomedical Science Symposium, March 8, 2007

McConnell, B.K., Mal, N., Forudi, F., Bautista, J., Jin, J-P., Popovic, Z., and Penn, M., Increased Cardiac Contractility in Response to Targeted Disruption of PKA/AKAP Interaction. Biophysical Society Meeting, March 3-7, 2007; Baltimore, MD

McConnell, B.K., Mal, N., Forudi, F., Bautista, J., Jin, J-P., Popovic, Z., and Penn, M., Targeted Disruption of PKA Binding to AKAPs Increases Cardiac Contractility and Decreases PKA-Dependent Phosphorylation, in vivo. Heart Failure Society of America (HFSA), September 10-13, 2006; Seattle, WA

McConnell, B.K., Mal, N., Popovic, Z., Forudi, F., Gladden, W., Penn, M., Bond, M. Targeted PKA-AKAP disruption using an adenoviral mediated peptide inhibitor increases contractility in normal rat hearts, in vivo. American Heart Association Scientific Sessions, November 13-16, 2005; Dallas, Texas

McConnell, B.K., Tan, F.L., Dai, Y., Ruse, C., Gladden, W., Skacel, M., Pettay, J.D.,Tubbs, R.R., Francis, G., Young, J.B., McCarthy, P.M., Moravec, C.S., and Bond, M. Discovery of a Heart-Specific and Failure-Associated Gene in Human Heart Failure. Second Annual Symposium of the American Heart Association Council on Basic Cardiovascular Science – Targeting Heart Failure: New Science, New Tools, New Strategies, July 23-27, 2005; Keystone, Colorado

Invited Presentations

University of Texas – Houston Medical School, Department of Integrative Biology and Pharmacology, Houston, TX; February 2009; Title: “Models of Cardiomyopathy and Altered Cardiac Contractility”

University of Houston, Biology and Biochemistry Undergraduate Association, Houston, TX; October 2008; Title: “Heart Disease: the translation of basic discoveries of cardiac signaling and function into clinical application”

University of Maryland School of Pharmacy Department of Pharmaceutical Sciences, Baltimore, MD; January 2008; Title: “Models of Cardiomyopathy and Altered Cardiac Contractility”

National Institute of Health (NIH), The National Center for Research Resources (NCRR) General Clinical Research Centers (GCRC), Bethesda, MD; November 2007; Title: “Models of Cardiomyopathy and Altered Cardiac Contractility”

Pennsylvania State University College of Medicine, Department of Cellular and Molecular Physiology, Hershey, PA; November 2007; Title: “Models of Cardiomyopathy and Altered Cardiac Contractility”

Food and Drug Administration (FDA), Center for Drug Evaluation and Research, Office of Clinical Pharmacology, White Oak, MD; October 2007; Title: “Models of Cardiomyopathy and Altered Cardiac Contractility”

Acidophil LLC / Red Abbey LLC, Baltimore, MD; October 2007; Title: “Models of Cardiomyopathy and Altered Cardiac Contractility”

Sun Health Research Institute (SHRI), Sun City, AZ; October 2007; Title: “Models of Cardiomyopathy and Altered Cardiac Contractility”

Jefferson Medical College, Center for Translational Medicine, Philadelphia, PA; October 2007; Title: “Models of Cardiomyopathy and Altered Cardiac Contractility”

Discussion Leader; Title: “New Capabilities, Emerging Issues and Responsible Conduct in Data Management”; Office of Research Integrity of the Department of Health and Human Services and the University of Maryland, Baltimore; ORI Data Management Conference (Sept. 28-29, 2006); Tremont Plaza Hotel; Baltimore, MD

Invited talk at the 1st International Meeting on Anchored cAMP Signaling Pathways in Berlin-Buch, Germany; October 15-16, 2005; Title: “Targeted Disruption of PKA and AKAP Interaction to Increase Cardiac Contractility using in vivo Gene Transfer”

University of Maryland School of Medicine, Baltimore, MD; February 2005; Title: “Heart failure: from mouse models of cardiomyopathy to myocardial gene transfer"

Poster Presentations

Biophysical Society 54th Annual Meeting (February 22, 2010); San Francisco, CA; Title: “Development of Non-Viral Gene Delivery Carriers for Ischemic Heart Disease (IHD)”

Summer Undergraduate Research Day, University of Houston (October 1, 2009); Houston, TX; Title: “Novel Bioreducible Polymeric Gene Delivery System for Ischemic Heart Disease”

Rice-Houston Alliance for Graduate Education and the Professoriate (AGEP) Symposium (August 6, 2009); Houston, TX; Title: “Cardiac Signaling: Targeted Disruption of Gravin (AKAP12)”

Cardiac and Vascular Cell Biology Second Annual Mini-Retreat (March 30, 2007); Baltimore, MD; Title: “Targeted Disruption of PKA and AKAP Interaction on Cardiac Contractility, PKA Phosphorylation, and TnI proteolysis in rat hearts in vivo”

16th Annual Perspectives in Biomedical Science Symposium (March 8, 2007); Baltimore, MD; Title: “Targeted Disruption of PKA and AKAP Interaction on Cardiac Contractility in Rat Hearts in vivo.”

Biophysical Society Meeting (March 3-7, 2007); Baltimore, MD; Title: “Increased Cardiac Contractility in Response to Targeted Disruption of PKA/AKAP Interaction”

Heart Failure Society of America (HFSA) (Sept. 10-13, 2006); Seattle, WA; Title: “Targeted Disruption of PKA Binding to AKAPs Increases Cardiac Contractility and Decreases PKA-Dependent Phosphorylation, in vivo.”

American Heart Association (Scientific Sessions 2005), Dallas, TX; Title: “Targeted PKA/AKAP disruption using an adenoviral mediated peptide inhibitor increases contractility in normal rat hearts, in vivo”

Membrane Biology Conference, University of Maryland, Harper’s Ferry, WV; Title: “Targeted PKA/AKAP disruption using an adenoviral mediated peptide inhibitor increases contractility in normal rat hearts, in vivo”

American Heart Association Council on Basic Cardiovascular Science – Targeting Heart Failure: New Science, New Tools, New Strategies, (July 2005); Keystone, CO; Title: “Discovery of a heart-specific and failure-associated gene in human heart failure”

Laboratory Members

  • Cori Wijaya, BS; Research Assistant
  • Andrea Diaz, BS; Research Assistant
  • Xing Yin, MD, PhD; Research Associate Fellow
  • Ashley Guillory, BS; PhD Graduate Student
  • Abeer Rababa’h, MS; PhD Graduate Student
  • Qiying Fan, BS; PhD Graduate Student
  • Habeeba Nizamdin, BS; PharmD Professional Student
  • Muhammad Siddiqui; Undergraduate Work-Study Student
  • Khadijah Bilal; Undergraduate Honors Student
  • Paul Tran; Undergraduate PURS Student
  • Amanda Sirisaengtaksin; Undergraduate Student
  • Minh Le; Undergraduate Student

Available Positions

Positions are available in the laboratory for (1) research technicians and (2) post-doctoral fellows wishing to help identify new and pertinent information regarding beta-adrenergic signaling mechanisms and its regulation of cardiac contractility in health and in cardiac disease, using molecular, biochemical, cellular and physiological technologies. Experience in calcium imaging, fluorescent microscopy, animal models of cardiac disease, molecular biology or biochemistry is preferred.

Please send a copy of your cover letter, CV, a brief statement of research interests, and contact information to: Bradley McConnell at bkmcconn@central.uh.edu.

Awards and Honors

  • Faculty Award for Excellence in Research, UH College of Pharmacy Faculty, 2013  
  • Elected Fellow, American Heart Association, and Fellow, AHA Council on Basic Cardiovascular Sciences
  • National Institutes of Health (NIH;NHLBI) R01 American Recovery and Re-Investment Act (ARRA) of 2009 Research Grant Supplement, Principal Investigator Targeted Disruption of Beta-Adrenergic Signaling to Increase Cardiac Contractility, 2009 - 2012
  • Graduate Research Supplement for Ashley Guillory (Ph.D., graduated 2012), B. McConnell (PI): Targeted Disruption of Beta-Adrenergic Signaling to Increase Cardiac Contractility, 2009-2013
  • National Institutes of Health (NIH;NHLBI) R01 Research Grant, Principal Investigator: Targeted Disruption of Beta-Adrenergic Signaling to Increase Cardiac Contractility, 2007-2013
  • State of Maryland OTRD (Other Tobacco Related Diseases) Research Grant, Association of Human β-Adrenergic Signaling Pathway mAKAP Gene Polymorphisms, 2006-2007
  • New Investigator Travel Award, at the Second Annual Symposium of the American Heart Association Council on Basic Cardiovascular Science – Targeting Heart Failure: New Science, New Tools, New Strategies, July 23-27, 2005; Keystone, Colo., 2005/li>
  • University of Maryland School of Medicine Intramural Research Grant, 2005-2006
  • American Heart Association (Mid-Atlantic) Beginning Grant-In-Aid, 2004–2006
  • Howard Hughes Medical Institute Post-Doctoral Research Fellowship, Harvard Medical School, 1997–2001
  • Finalist, Student Research Achievement Award—Honorable Mention (Biophysical Society Meeting), 1996
  • National Institutes of Health (NIH) Training Grant Science Award (T32), CWRU, 1993–1997
  • Academic Scholarship, Department of Physiology & Biophysics, CWRU, 1991–1993
  • Hammond Academic Scholarship, Department of Biology, Pennsylvania State University, 1990–1991