David C. Kem, MD
George Lynn Cross Research Professor
Dr. Kem's Research Group
The Childrens Hospial/Everett Tower
1200 N. Everett Drive
Oklahoma City, OK 73104-5068
(405) 271-5896 ext 47789
Clinical: Endocrine hypertension, adrenal diseases, and renovascular hypertension. Diagnostic tests for primary hyperaldosteronism, which was first described by Dr. Kem's mentor Dr. Jerome Conn. Extra (aberrant) renal arteries and hypertension: identification of a new syndrome wherein an aberrant renal artery is associated with elevated renin activity and hypertension despite no evidence for localized arterial narrowing
Research: Goal: To bridge the gap between basic research into hormonal mediated G-protein receptor pathophysiology and clinical outcomes in cardiovascular diseases.
We have identified an ischemia-induced loss of an enzyme (G-protein receptor kinase, GRK2) that plays a major role in protecting the heart from arrhythmias. This deficiency occurs within hours of the myocardial ischemia, leaving the ischemic tissue hyper-responsive to beta -adrenergic stimulation and prone to fatal arrhythmias. We are defining the mechanism for this deficiency and have identified several effective pharmacologic interventions.
A second project, funded by the VAMC, is directed toward identifying the mechanism by which hyperglycemia may lead to complications of diabetes mellitus that lead to 1) desensitization of the heart and 2) desensitization of receptors in blood vessels in the eye to G-protein-mediated hormones such as norepinephrine and angiotensin II. These studies use in vitro cell cultures and mice with STZ-induced Type 1 diabetes mellitus. They employ MRI/MRS technology transgenic mice with genetically altered function of PKCbeta and/or GRK2.
Dr. Kem has helped develop and sustain the annual A Kurt Weiss Lectureship in Biomedical Ethics, a monthly Medical Ethics grand rounds for medical students. He is an advisor to the local chapter of the Christian Medical and Dental Association. He has strong family interactions, and has 5 children and 21 grandchildren.
||NIH trainee in Endocrinology, Metabolism and Hypertension: Mentor, Jerome Conn MD, University Hospitals, University of Michigan, Ann Arbor, MI
||Specialty postdoctoral education, Internal Medicine, University Hospitals, University of Michigan, Ann Arbor, MI
||MD - College of Physicians & Surgeons, Columbia University, New York City, NY
||BA - Earlham College, Richmond, Indiana
Hongliang Li, Benjamin J. Scherlag, David C. Kem, Caitlin Zillner, Shailesh Male, Sorkko Thirunavukkarasu, Xiaohua Shen, Alexandria Benbrook, Jan V. Pitha, Ralph Lazzara and Xichun Yu. The Propensity for Inducing Atrial Fibrillation: A Comparative Study in Old versus Young Rabbits. J of Aging Research (in Press)
Hongliang Li, MD, PhD; Xichun Yu, MD; Campbell Liles, BS; Muneer Khan, MD; Megan Vanderlinde-Wood, MD; Allison Galloway, MD; Caitlin Zillner, BS; Alexandria Benbrook, BS; Sean Reim, BS; Daniel Collier, BS; Michael A. Hill, PhD; Satish R. Raj, MD; Luis E. Okamoto, MD; Madeleine W. Cunningham, PhD; Christopher E. Aston, PhD; David C. Kem, MD. Autoimmune Basis for Postural Tachycardia Syndrome (POTS). J Am Heart Assoc. 2014;3:e000755. Originally published February 26, 2014. doi: 10.1161/JAHA.113.000755
Hongliang Li, Benjamin Scherlag, David Kem, Alexandria Benbrook, Xiaohua Shen, Madeleine Cunningham, Ralph Lazzara, Christopher Aston, and Xichun Yu. Inducible cardiac arrhythmias caused by enhanced β1-adrenergic autoantibody expression in the rabbit. Am J Physiol Heart Circ Physiol 2013 Nov 22. [Epub ahead of print] PMID: 24271491
Li H, Zuccolo J, Kem DC, Zillner C, Lee J, Smith K, James JA, Cunningham MW, Yu X. Implications of a vasodilatory human monoclonal autoantibody in postural hypotension. J Biol Chem 2013 Sep 16. [Epub ahead of print] PMID:24043632
Xichun Yu; Stavros Stavrakis; Shijun Huang, Michael A. Hill, Shijun Huang, Sean Reim, Hongliang Li, Muneer Khan, Sean Hamlett; Madeleine W. Cunningham; David C. Kem: Autoantibody Activation of Beta-Adrenergic and Muscarinic receptors Contributes to an "Autoimmune" Postural Hypotension. J Amer Soc. Hypertension. 2012;6:40-47.
Hongliang Li, David C. Kem, Sean Reim, Muneer Khan, Megan Vanderlinde-Wood, Caitlin Zillner, Daniel Collier, Campbell Liles, Michael A. Hill, Madeleine W. Cunningham, Christopher E. Aston, Xichun Yu: Agonistic Autoantibodies as Vasodilators in Orthostatic Hypotension: A New Mechanism. Hypertension 2012;59(2):402-408.
Hongliang Li, MD, PhD; Benjamin J. Scherlag, PhD; David C. Kem, MD; Caitlin Zillner, BS; Shailesh Male, MD; Sorkko Thirunavukkarasu, MD; Xiaohua Shen, MD; Jan V. Pitha, Madeleine W. Cunningham, PhD; Ralph Lazzara, MD; Xichun Yu, MD. Atrial Tachycardia Provoked in the Presence of High Titers of Activating Autoantibodies for Beta2-Adrenergic Receptor in the Rabbit. Heart Rhythm, http://dx.doi.org/10.1016/j.hrthm.2012.11.010
Yu X, Stavrakis S, Huang S, Patterson E, Hill MA, Hamlett S, Lazarra R, Cunningham MW, and Kem DC. (2011). Autoantibody Activation of Beta-Adrenergic and Muscarinic Receptors Contributes to an "Autoimmune" Postural Hypotension. Hypertension. Resubmission requested.
Stavrakis S, Kem DC, Patterson E, Lozano P, Huang S, Szabo B, Cunningham MW, Lazzara R, and Yu X. (2010). Opposing Cardiac Effects of Autoantibody Activation of Beta-Adrenergic and M2 Muscarinic Receptors in Cardiac Related Diseases. Int J Cardiol Jan. 5. (Epub ahead of print.)
Yu X, and Kem DC. (2010). Proteasome inhibition during myocardial infarction. Cardiovasc Res 85(2): 312-320.
Stavrakis S, Yu X, Patterson E, Huang S, Hamlett S, Chalmers L, Pappy R, Cunningham M, Morshed S, Davies TF, Lazzara R, and Kem DC. Activating Autoantibodies to the Beta-1 Adrenergic and M2 Muscarinic Receptors Facilitate Atrial Fibrillation in Patients with Graves' Hyperthyroidism. J Amer Col Card 54:14, 1309-1316, 2009.
Yu X, Patterson E, Stavrakis S, Huang S, De Aos I, Hamlett S, Cunningham MW, Lazarra R, and Kem DC. Development of Cardiomyopathy and Atrial Tachyarrhythmias Associated with Activating Autoantibodies to Beta-Adrenergic and Muscarinic Receptors. J Amer Soc Hypertension 3(2) 133-140, 2009.
Yu X, Patterson E, Stavrakis S, De Aos I, Hamlett S, Cunningham MW, Lazzara R, Kem DC. Development of Cardiomyopathy and Atrial Tachyarrhythymias in a Hypertensive Patient with Activating Autoantibodies to Beta-Adrenergic and Muscarinic Receptors. JASH, In Press.
Heflin LA, Street CB, Papavassiliou DV, Kem DC, Wu D, O’Rear EA. Transient Stenotic-like occlusions as a possible mechanism for renovascular hypertension due to aneurysm. JASH. Submitted.
Yu X, Patterson E, and Kem DC. Targeting Proteasomes for Cardioprotection. Current Opinion in Pharmacology. In Press.
Stavrakis S, Kem DC, Patterson E, Lozano P, Huang S, Szabo B, Cunningham MW, Yu X. Opposing cardiac effects of autoantibody activation of beta-adrenergic and M2 muscarinic receptors in cardiac related diseases. JACC Submitted.
Mascaro-Blanco A, Yu X, Lindenfeld J, Olansky L, Lyons T, Duvall D, Heuser JS, Rubenstein CJ, Cooper LT, Kem DC, Cunningham MW. Consequences of unlocking the cardiac myosin molecule in human myocarditis and cardiomyopathies. Autoimmunity, In Press 2008.
Huang S, Patterson E, Yu X, Garrett MW, Kem DC. Proteasome inhibition one hour following ischemia protects GRK2 and prevents malignant ventricular tachyarrhythmias and SCD in a canine model of myocardial infarction. Am J Physiol Heart Circ Physiol. 2008;294(3):H1298-1303.
Kem DC, Yu X, Patterson E, Huang S, Stavrakis S, Szabo B, Olansky L, McCauley J, Cunningham MW. An autoimmune hypertensive syndrome. Hypertension 50:829-834, 2007.
Kem DC, Metcalf JP, Cornea A, Dunnam M, Engelbrecht A, Yu X. Is pseudocushings syndrome in a critically ill patient pseudo? Endocr Pract 2007;13(2):153-158.
Yu X, Tesiram YA, Towner RA, Abbott A, Patterson E, Huang S, Garrett MW, Chandrasekaran S, Matsuzaki S, Szweda LI, Gordon BE, Kem DC. Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI). Cardiovasc Diabetol 2007;6:6.
Patterson E, X Yu, S Huang, MW Garrett and DC Kem. Suppression of autonomic-mediated triggered firing in pulmonary veins, 24 hrs post coronary artery ligation in the dog. J Cardiovasc Electrophysiol. 17(7):763-70, 2006.
Yu X, Huang S, Patterson E, Garrett, M W, Kaufman K W, Zhe M, Dunn S T, Kem D C. Proteasome Degradation of GRK2 During Ischemia and Ventricular Tachyarrhythmias in a Canine Model of Myocardial Infarction, Am J Physiol/Heart Circ Physiol, 289(5):H1960-967, 2005.
Yu X, Patterson E, Huang S, Garrett M W, Kem DC. TNF?, Rapid Ventricular Tachyarrhythmias and Infarct Size in Canine Models of Myocardial Infarction. J Cardiovasc Pharmacology;45:153-159, 2005.
Kem, DC, D Lyons, J Wenzl, D Halverstadt, X Yu, MD. Renin Dependent Hypertension Due To Nonfocal-stenotic Aberrant Renal Arteries: Proof Of A New Syndrome; Hypertension; 46:380-385, 2005. (with accompanying editorial by ed.)