Professor of Biochemistry and Molecular Medicine
Professor of Medicine (Secondary)
Office Phone: 202-994-0501
Department: Biochemistry and Molecular Medicine
- BS, Loyola College, 1958
- MD, University of Maryland School of Medicine, 1962
After completing a medical residency at Georgetown University Hospital in 1964 he completed a Cardiology fellowship in 1966 at Duke University where he trained in clinical cardiac catheterization and pharmacology basic research. He was then appointed as a research associate at NIH's NICHHD and the McCollum Pratt Institute of the Johns Hopkins University where he studied the cardiac pathobiology of alpha tocopherol deficiency. In 1966 He joined Harvard's Peter Bent Brigham Hospital Department of Medicine's Cardiovascular Research unit, and rose from Instructor to Associate Professor in 1975. There he concentrated his research on the role of phospholipases of the heart in the ischemic pertubation of cardiac membrane phospholipids and organelles which led to several RO1 NIH grant awards. With his research team he moved to the Medical College of Virginia/VCU in 1975 as chairman of the Department of Biophysics and served as a professor of Medicine (Cardiology); there he was active in teaching medical and mentoring graduate students, while publishing a series of manuscripts on cardiac lysosomal activity in myocardial ischemia and the distribution of phospholipases in cardiac mitochondria and sarcolemmal membranes, and overseeing a new NHLBI Training Grant on molecular mechanisms of cardiovascular injury. To pursue the emerging research in free radicals of the heart he moved to the Oklahoma Medical Research Foundation where his Cardiovascular Program research team participated in the application of electron spin trapping methodology to identify superoxide and other reactive oxygen species in myocardial injury and in free radical-induced lipid peroxidative injury of subcellular organelles. In 1985 he was appointed Professor of Medicine (Cardiology) and Physiology at GW's School of Medicine and Health Sciences as Director of the new Division of Experimental Medicine; he and his research team established new collaborations with fellow SMHS research faculty to successfully compete for the award of a Program Project Grant from the NHLBI that concentrated on: free radical mechanisms of cardiovascular injury, the antioxidant properties of beta blocker and othe cardiovascular drugs, and the role of magnesium deficiency in causing cardiomyopathy;importantly, the cause of this latter cardiovascular pathology was soon discovered to be due to neurogenic inflammation, due to the hypomagnesemia-related release of substance P from sensory nerves, that triggered production of excessive systemic free radical injury. This finding was confirmed by the use of NK1-receptor blocking agents that significantly protected cardiac and other tissue injury due to substance P. Our more recent Research Interests (below), focusing on anticancer drug toxicity/side effects, identified the significant protection by aprepitant (Emend),a clinically used NK1- blocking antinausea drug, against the impairment of cardiac ventricular dysfunction and cutaneous lesions caused by aprepitant (Tarceva), a tyrosine kinase inhibitor used to treat lung cancer.
1996-2006: Elected Secretary, President Elect and President of the International Society for Heart Research (ISHR) American/Canada Section
2007: President's Lecture, ISHR Congress, Italy
2002-2008: Co-Chair/Chair: Gordon Conference on Magnesium in Biochemical Processes and Medicine
2004: Seeling Research Prize, American College of Nutrition
2008: John Foerster Award for Contributions in Cardiovascular Medicine, by the Faculty of Medicine, the University of Manitoba, Canada
1990: President, the Oxygen Club of Greater Washington
1996-2006: King Fahd Professor of Cardiac Pathobiology
1988-1994: Member, Board of Directors, American Heart Association, Nation's Capital
2017: Lifetime Achievement Award in Cardiovascular Science, Medicine and Surgery, The International Academy of Cardiovascular Sciences
At the Medical College of Virginia, VCU, from 1975-1981: Course director/lecturer: (first/second year medical students) cardiovascular physiology for six years. Also mentoring Biophysics PhD graduate students
At GW SMHS, Course director/lecturer 1990-2004: Spring Semester freshman medical student Physiology Course.
1986-2015: teaching medical students, residents and cardiology fellows in clinic and hospital rounds.
Our research team studies mechanisms of cardiovascular injury due to oxidative and nitrosative stress. Some key techniques/models employ tissue culture, antioxidant interventions and long-term treatment with chemotherapy agents, immunohistochemical characterization of apoptosis and inflammation, genetically engineered mice and echocardiography of impaired cardiac function. We identified substance P as a key mediator of inflammation of the heart due to magnesium deficiency, as well as cardioprotection from drugs that block neuropeptide release and the NK1 receptor for substance P. Currently we are studying the role of the neutral endopeoptidase, neprilysin, in amplifying neurogenic inflammation during hypomagnesemia; our lab is the first to report inhibition of this enzyme, which is critical for degrading excess substance P, due to the oxidative/nitrosative stress of hypomagnesemia. Recently we reported on the cardiotoxicity of tyrosine kinase inhibiting chemotherapeutic agents; this work resulted in funding of an NHLBI grant entitled “EGFR Tyrosine Kinase Inhibition-Induced Cardiomyopathy.” These recent studies may have translational relevance to the newly evolving joint cardiology-oncology emphasis on treating cardiovascular disease in long term cancer survivors.
View publications by this faculty member.
Mak, I.-T, Kramer, J.H., Chmielinska, J.J, Spurney, C.F., Weglicki, W.B. The EGFR TKI, erlotinib, causes hypomagnesemia, oxidative stress and cardiac dysfunction: attenuation by substance P-receptor blockade. J. Cardiovasc. Pharmacol. In Press. 2014.
Weglicki, W.B., Mak, I-T., Chmielinska, J.J., Spurney, C.F., Kramer. J.H. Hypomagnesemia-induced neurogenic inflammation and cardiac dysfunction during experimental Mg deficiency. In: Proceedings of the 13th International Magnesium Symposium. Merida, Yucatan, Mexico. In Press. 2014.
McCaffrey, T.A., Tziros, C., Lewis, J., Katz, R., Siegel, R., Weglicki,W., Kramer, J., Mak, I-T., Toma, I.,Chen, L., Benas, E., Lowitt, A., Rao, S., Witkins, L., Lian, Y., Lai, Y.,Yang, Z., Fu, S.W. Genomic Profiling Reveals the Potential Role of TCL1A and MDR1 Deficiency in Chemotherapy-Induced Cardiotoxicity. Int. J. Biol. Sci. 9(4):350-360, 2013.
Mak, I.-T, Kramer, J.H., Chen X., Chmielinska, J.J, Spurney, C.F., Weglicki, W.B. Mg-supplementation Attenuates Ritonavir-induced Hyperlipidemia, Oxidative Stress and Cardiac Dysfunction in Rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305: R1102–R1111, 2013.
Weglicki, W.B. Hypomagnesemia and Inflammation: Clinical and Basic Aspects. Ann. Rev. of Nutrition 32:4.1-4.17;2012. (in press).
Weglicki, W.B. Kramer, J.H., Spurney, C.F., Chmielinska, J.J., Mak, I.T. The EGFR Tyrosine Kinase Inhibitor Tyrphostin AG-1478 Causes Hypomagnesemia and Cardiac Dysfunction. Can. J. of Physiol. & Pharmacol. (accepted 1/20/2012) (in press).
Mak I.T. Chmielinska, J.J, Kramer, J.H. Spurney, C.F., Weglicki, W.B. Loss of neutral endopeptidase activity contributes to neutrophil activation and cardiac dysfunction during chronic hypomagnesemia: Protection by substance P receptor blockade. Exp. & Clin. Cardiol. 16(4):121-124, 2011.
Weglicki, W.B., Mak, I.-T., Chmielinska, J.J., Tejero-Taldo, M.I., Komarov, A., Kramer, J.H. The role of Magnesium Deficiency in Cardiovascular and Intestinal Inflammation. Magnes. Res. 23(4):199-206, 2010. PMID # 20971697
Kramer, J.H., Spurney, C., Iantorno, M., Tziros, C., Mak, I-T., Tejero-Taldo, M.I., Chmielinska, J.J., Komarov, A.M., Weglicki, W.B. Neurogenic inflammation and cardiac dysfunction due to hypomagnesemia in a rodent model. Am. J. Med. Sci. 338: 22-27, 2009.
Weglicki, W.B., Chmielinska, J.J., Tejero-Taldo, M.I., Kramer, J.H., Spurney, C., Viswalingham, K., Lu, B., Mak, I.-T. Neutral endopeptidase inhibition enhances substance P mediated inflammation due to hypomagnesemia. Magnes. Res. 22: 1-7, 2009.
Mak, I. T., Chmielinska, J.J., Kramer, J.H., Weglicki. W.B. AZT-Induced cardiovascular toxicity - attenuation by Mg-supplementation. Cardiovascular Toxicol. 9(2): 78-85,2009.
Weber, KT, Weglicki, W.B. and Simpson, RU. Macro- and Micronutrients Dyshomeostais in the Adverse Structural Remodeling of Myocardium. Cardiovasc. Res. 81(3): 500-508, 2009
Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.