I. Tong Mak
Research Professor of Biochemistry and Molecular Medicine
Research Professor of Medicine (Secondary)
Office Phone: 202-994-3539
Department: Biochemistry and Molecular Medicine
- BS, University of Wyoming, 1974
- MS, Michigan State University, 1977
- PhD, University of Wisconsin, 1982
Originally, from Hong Kong, Dr. I.Tong Mak Obtained his Ph.D. in Biochemistry and Life Sciences from University of Wisconsin-Madison (1982) with his Thesis focused on mitochondrial energy metabolism. He continued to receive his post-doc training at Oklahoma Medical Research Foundation (1982-85) in cardiovascular biochemistry, broadly on the roles of ROS/nitric oxide products, and antioxidant defense. He joined GW Dept. of Medicine in 1985 and became a research faculty in Dept. of Physiology and Experimental Medicine in 1986. Since 2004, he joined the Dept. of Biochemistry, and promoted to Research Professor of Biochemistry and Molecular Medicine since 2007. His research interests focus on cardiovascular injury and dysfunction, contribution of Mg-deficiency, lysosomal iron and drug toxicity, the role of neurogenic/systemic inflammation, oxidative/nitrosative stress and antioxidant therapy. Since 2006, additional focus has been on the effects of anti-HIV drug, and HIV infection on the systemic/cardiac responses. For the latter efforts, our team (Mak as PI) has been awarded 3 NIH grants (2006, 2010, 2014) to study the metabolic, oxidative and cardiac stress effects and the impact of Mg-supplementation on the related gene disregulation (lipogenic and Nrf2-related antioxidant pathway). For the HIV research efforts, several papers have been published in good impact journals (Am. J. Physiol. Free Radical Biol. Med., Int. J. Mol. Sci. Plos One). More recently, Mak’s effort has been on the side effects (cardiovascular and cutaneous toxicity) of anti-cancer drugs such as EGFR-TKIs and the role of SP-mediated NK-1 receptor pathway. Mak has published >90 scientific papers, some in high impact journals including J. Clin Invest, J. Biol. Chem. Circulation Research, Free Radical Biol. Med. Mak also served as a Study Review Member on an NIHLBI Special Emphasis Panel: Basic Research in HIV-Related Heart Lung and Blood Disease, in 2015.
View Publications on PubMed
NIH R21HL125038: “HAART-mediated Cardiovascular Toxicity in HIV-Transgenic Rats: Mg Protection” (2014-2018). PI: Mak, I.T.
Collaborative Clinical Research Proposal: “Magnesium Treatment of Inflammation in Disorder of Glucose Homeostasis.” Kuwait Foundation for the Advancement of Sciences. (2013-2018). PI: Weglicki; Co-I: Mak, I. T.
GWU Biochemistry McCormick Genomics and Proteomics Supplemental Grant- “Prevention of EGFR Inhibitor-Mediated Dermatitis, Cardiac Dysfunction and Genomic Alterations using Neurokinin-1 Receptor Blockade” (2017 to 2018) PI: Mak IT
NIH R21NR012649: “Cardioprotective Efficacy of Mg-Supplementation during HAART Therapy” (2010-2013) P.I. Mak, I.T.
1982-1985 National Research Service Award Fellowship, Cardiovascular Research Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, OK
1998 Co-Inventor for US Patent #5776985 “Fluorinated Propranolol and Related Methods”
2016-2017: Co-Inventor for US Patent Application No. 15/278,192
Title: Use of NK-1 Receptor Antagonists for Treating Hypomagnesemia, Neurogenic Inflammation, and Cardiac Dysfunction Associated With EGFR-Blocking Drugs.
2019: Second Prize Award in the 2019 GW Technology Commercialization Innovative Competition as a Co-inventor presentation, “Apprepitant (Emend) Prevents Cutaneous Inflammatory and Cardiac Dysfunction due to Erlotinib (Tarceva).
Currently there are 2 separate research projects ongoing in our laboratory, all in the general areas of cardiovascular and renal oxidative inflammation and therapy. (1) Highly active antiretroviral agents and/or HIV-mediated Cardiac Dysfunction and Protective Efficacy of Magnesium (PI): This project focuses on currently used anti-HIV agents (including NRTIs, NNRTIs and protease inhibitors) -mediated systemic oxidative events (e.g. neutrophil and endothelial activation, iNOS induction, inflammatory cytokine upregulation) and lipid metabolic disturbances leading to cardiovascular dysfunction (by echocardiography) and pathology, and potential protective mechanisms of Mg. Both cultured endothelial cells and relevant rodent models have been used. The roles of hypomagnesemia and SP-mediated neurogenic inflammatory cascade, and the protective efficacy and mechanisms of Mg are investigated. More recent efforts have focused on gene disregulation related to lipid metabolism and the Nfr2 mediated antioxidant defense pathway. (2) EGFR Tyrosine Kinase Inhibitors - Induced Cardiomyopathy and cutaneous toxicity: This project focuses on if chronic EGFR-TKI (e.g. erlotinib) treatment may induced hypomagnesemia and subsequent cardiac inflammation/dysfunction and dermitis in rats; and if the TKI-induced systemic pathogenesis and cardiac dysfunction and cutaneous toxicity can be attenuated by the clinically-used Substance P receptor blocker. We received a US patent award for the latter effort in 2016; we plan to continue this pre-clinical effort towards a potential clinical therapy for cancer patients receiving EGFR inhibition therapy in the near future.
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 WB, Kramer JH, Chmielinska JJ, Spurney CF, Mak IT. “The EGFR tyrosine kinase inhibitor tyrphostin AG-1478 causes hypomagnesemia and cardiac Dysfunction.” Can. J. of Physiol. & Pharmacol. (accepted 1/20/2012)
Weglicki WB, Chmielinska, JJ Tejero-Taldo MI, Kramer, Mak IT. Cardiovascular and intestinal responses to oxidative and nitrosative stress during prolonged magnesium deficiency. Am J Med Sci 342: 125-128. 2011
Mak IT, Chmielinska JJ, Kramer JH, Spurney CF, Weglicki WB. 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.
Mak IT, Chmielinska JJ, Kramer JH, Weglicki WB. AZT-induced oxidative cardiovascular toxicity—attenuation by Mg-supplementation. Cardiovasc. Toxicol. 2009; 9(2):78-85.
Mak IT, Kramer JH, Chmielinska JJ et al. Inhibition of neutral endopeptidase potentiates neutrophil activation during Mg-deficiency in the rat. Inflammation Res. 57: 300-305, 2008.
Mak IT, Chmielinska JJ, Torres A, Weglicki WB. D-propranolol attenuates lysosomal iron accumulation and oxidative injury in endothelial cells. J Pharmacol Exp Ther. 317:522-508, 2006.
Mak IT, Weglicki WB. Potent antioxidant properties of 4-OH-propranolol. J Pharmacol Exp Ther.; 308: 85-90, 2005.
Tejero-Taldo MI, Chmielinska JJ, Gonzalez G, Mak IT, Weglicki WB. N-Methyl-D-aspartate receptor blockade inhibits cardiac inflammation in the Mg-deficient rat. J Pharm. Exp. Ther. 2004; 311: 8-13.
Mak IT, Goldfarb MG, Weglicki WB, Haudenschild CC. Cardiac pathologic effects of AZT in Mg-deficient mice. Cardiovasc. Toxicol 4: 169-178, 2004.
Dickens BF, Weglicki WB, Boehme P, Mak IT. Antioxidant and lysosomotropic properties of acridine-propranolol: Protection against oxidative endothelial injury. J. Mol Cell Cardiol. 34: 129-137, 2002.
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.