• Lab Members
• Former Lab Members
• Redox Signaling
• Pulmonary Hypertension and Right Heart Failure
• Integrative Cardio-Pulmonary Biology Workshops

Yuichiro Justin Suzuki, Ph.D.

Professor

Editorial Board Member, Antioxidants & Redox Signaling

Editorial Board Member, Pulmonary Circulation

Editorial Board Member, Physiological Reports

Consulting Editor, Pharmacology Research and Perspectives

Faculty Member, Respiratory Pharmacology Section, FACULTY OF 1000

Council Member, Oxygen Club of Greater Washington DC

2006 President, Oxygen Club of Greater Washington DC

Nataliia V. Shults, MD,PhD

                                Former Lab Members

Nurefsan Sariipek (Summer 2019)
Sarah Seeherman (Summer 2019)
Jaquantey Bowens
Adenike Falade
Oleksiy Melnyk
Sergey S. Kanovka
Jennifer Ten Eyck
Faisal Almonsour
Camilla Cucinotta
Zeynep Postalcioglu 
Makhosazane Zungu-Edmondson, Ph.D.
Dividutta Das, M.S.
Xinhong Wang, M.D.,Ph.D.
Yasmine Ibrahim, M.D.,Ph.D.
Yi-Hsuan Wang
Cheng-Ying Hsieh, Ph.D.
Chi-Ming Wong, Ph.D.
Geetanjali Bansal, Ph.D.
Joel Lee
Hasan Ulusoy, M.D.
Lobsang Trasar, M.D.
Aria Hong, M.D.
Quinn Caslow
Brent A. Gilmore, M.D.
Duncan T. Vincent, M.D.
Ludmila Jelinkova, M.D.
Haibei Luo, Ph.D.
Lingling Liu, M.D.
Emanuel Lubart
Ah-Mee Park, Ph.D.
Shilpashree Vinod Kumar, M.S.
Vivek Jain, M.D.
Hiroko Nagase, M.S.
Nava Szwergold
Kaitlyn Webster
Joanne Lee
Matthew Wester
Karen Pitlyk
Young Lee
Kai Nie
Drazenka Nemcic-Moerl
Jason Tilan, M.S.
Tufani SenGupta
Jill Angelosanto
Aiguo Ma, M.D.
Jianli Guo, M.D.
Chia Chi Tan
Tor Sandven
Yuri Kim
Melissa DeMarko
Julie Lum
Katrina Claridad
Heather Schmitz
Sarah Fitch
Sophie Clement, Ph.D.
Naohiro Hamaoka, M.S.
Jane Remeika
Sarah Leatham
Kazumi Kitta, Ph.D.
Susan Shi


Grants:

              NIH R01 HL072844
              NIH R21 AI142649
              NIH R03 AG059554
              NIH R03 AA026516


                                                           Redox Signaling

    Reactive oxygen species are known to be damaging to various biological systems. 20 years ago, we and others postulated that reactive oxygen species also mediate signal transduction. While this idea is now well established, the molecular mechanism of how reactive oxygen species promote cell signaling is unknown. My laboratory recently discovered that a process of protein oxidation called carbonylation plays an important role in the molecular mechanism of reactive oxygen species signaling.
 
 Suzuki YJ, Marcocci L, Shimomura T, Tatenaka Y, Ohuchi Y, Brelidze TI. Protein Redox State Monitoring Studies of Thiol Reactivity. Antioxidants. 2019 May 22;8(5). pii: E143. doi: 10.3390/antiox8050143.
 
Marcocci L, Suzuki YJ. Metabolomics Studies to Assess Biological Functions of Vitamin E Nicotinate. Antioxidants. 2019 May 11;8(5). pii: E127. doi: 10.3390/antiox8050127.
 
Ahmad T, Suzuki YJ. Juglone in Oxidative Stress and Cell Signaling. Antioxidants. 2019 Apr 5;8(4). pii: E91. doi: 10.3390/antiox8040091.
 
Suzuki YJ. Oxidant-Mediated Protein Amino Acid Conversion. Antioxidants. 2019 Feb 25;8(2). pii: E50. doi: 10.3390/antiox8020050.
 
Suzuki YJ, Shults NV. Redox Signaling in the Right Ventricle. Adv Exp Med Biol. 2017;967:315-323. doi: 10.1007/978-3-319-63245-2_19.
 
YJ, Almansour F, Cucinotta C, Rybka V, Marcocci L. Cell signaling promoting protein carbonylation does not cause sulfhydryl oxidation: Implications to the mechanism of redox signaling. F1000Res. 2017 Apr 10;6:455. doi: 10.12688/f1000research.11296.1. eCollection 2017.
 
Duncan KR, Suzuki YJ. Vitamin E Nicotinate. Antioxidants. 2017 Mar 13;6(1). pii: E20. doi: 10.3390/antiox6010020.

Suzuki YJ, Hao JJ. Evidence for the oxidant-mediated amino acid conversion, a naturally occurring protein engineering process, in human cells. F1000Res. 2017;6:594. doi: 10.12688/f1000research.11376.1.
 
Suzuki YJ, Almansour F, Cucinotta C, Rybka V, Marcocci L. Cell signaling promoting protein carbonylation does not cause sulfhydryl oxidation: Implications to the mechanism of redox signaling. F1000Res. 2017;6:455. doi: 10.12688/f1000research.11296.1.

Wang X, Shults NV, Suzuki YJ. Oxidative profiling of the failing right heart in rats with pulmonary hypertension. PLoS One. 2017;12:e0176887. doi: 10.1371/journal.pone.0176887.

Duncan KR, Suzuki YJ. Vitamin E nicotinate. Antioxidants. 6. pii:E20. doi: 10.3390/antiox6010020.
 
Das D, Wang YH, Hsieh CY, Suzuki YJ. Major vault protein regulates cell growth/survival signaling through oxidative modifications. Cell Signal. 28:12-18, 2016
 
Wong CM, Marcocci L, Das D, Wang X, Luo H, Zungu-Edmondson M, Suzuki YJ. Mechanism of protein decarbonylation. Free Radic Biol Med 65:1126-1133, 2013
 
Bansal G, Das D, Hsieh CY, Wang YH, Gilmore BA, Wong CM, Suzuki YJ. IL-22 activates oxidant signaling in pulmonary vascular smooth muscle cells. Cell Signal 25:2727-2733, 2013

Wong CM, Bansal G, Marcocci L, Suzuki YJ. Proposed role of primary protein carbonylation in cell signaling. Redox Rep 17:90-94, 2012

Bansal G, Wong CM, Liu L, Suzuki YJ. Oxidant signaling for interleukin-13 gene expression in lung smooth muscle cells. Free Radic Biol Med 52:1552-1559, 2012.


Suzuki YJ. Cell signaling pathways for the regulation of GATA4 transcription factor: Implications for cell growth and apoptosis. Cell Signal 23:1094-1099, 2011.

Park AM, Wong CM, Jelinkova L, Liu L, Nagase H, Suzuki YJ. Pulmonary hypertension-induced GATA4 activation in the right ventricle. Hypertension 56:1145-1151, 2010

Wong CM, Marcocci L, Liu L, Suzuki YJ. Cell signaling by protein carbonylation and decarbonylation. Antioxid Redox Signal 12:393-404, 2010

Suzuki YJ, Carini M, Butterfield DA. Protein carbonylation. Antioxid Redox Signal 12:323-325, 2010

Liu L, Marcocci L, Wong CM, Park AM, Suzuki YJ. Serotonin-mediated protein carbonylation in the right heart. Free Radic Biol Med 45:847-854, 2008

Wong CM, Cheema AK, Zhang L, Suzuki YJ. Protein carbonylation as a novel mechanism in redox signaling. Circ Res 102: 310-318, 2008

Park AM, Nagase H, Kumar SV, Suzuki YJ. Effects of intermittent hypoxia on the heart. Antioxid Redox Signal 9:723-729, 2007

Park AM, Suzuki YJ. Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice. J Appl Physiol 102:1806-1814, 2007

Park AM, Nagase H, Vinod Kumar S, Suzuki YJ. Acute intermittent hypoxia activates myocardial cell survival signaling. Am J Physiol 292:H751-H757, 2007

Suzuki YJ, Jain V, Park AM, Day RM. Oxidative stress and oxidant signaling in obstructive sleep apnea and associated cardiovascular diseases. Free Radic Biol Med 40:1683-1692, 2006
 
Suzuki YJ, Forman HJ, Sevanian A. Oxidants as stimulator of signal transduction. Free Radic Biol Med 22: 269-285, 1997 Cited >1,000 times

                                Pulmonary Hypertension and Right Heart Failure
   My laboratory investigates signal transduction and transcriptional regulatory mechanisms for growth and death of pulmonary vascular smooth muscle cells and right ventricular cardiac muscle cells. Our goal is to develop therapeutic strategies to treat patients with pulmonary hypertension. Pulmonary hypertension is a devastating disease without cure, characterized by increased blood pressure in pulmonary circulation due to increased vasoconstriction and cell growth. Increased pulmonary vascular resistance eventually leads to right heart failure and death.
   Apoptosis-based therapy to regress pulmonary vascular thickening: Patients who are diagnosed with pulmonary hypertension are often at late stage with dramatically increased pulmonary vascular wall thickness. The major goal of our laboratory is to develop therapeutic strategies to regress vascular thickening in order to reduce pulmonary arterial pressure using apoptosis-based technologies, which have been used in cancer therapy. In this regard, our laboratory (i) investigates basic mechanisms of cell apoptosis and survival in normal and remodeled pulmonary vascular smooth muscle, (ii) explores effective apoptotic agents for regressing pulmonary vascular thickening, and (iii) develops useful drug delivery systems to specifically elicit apoptosis in pulmonary vascular smooth muscle. Our laboratory currently focuses on targeting Bcl-xL in remodeled pulmonary vascular smooth muscle.
   Mechanisms of apoptosis in right ventricular cardiac myocytes: The major cause of death for pulmonary hypertension patients is right heart failure, as elevated pulmonary vascular resistance puts load to the right ventricle. The right ventricle initially responds to pressure overload by thickening the ventricular wall to strengthen muscle contraction, however, this cardiac hypertrophy event is followed by transition to thinning of the ventricular wall and heart failure. Apoptosis of right ventricular myocytes may play important roles in transition from hypertrophy to failure as well as in drug-induced cardiotoxicity, which might occur during apoptosis-based therapy to regress pulmonary vascular thickening. Our laboratory, therefore, studies the mechanisms of right ventricular myocyte apoptosis while focusing on the role of GATA-4 transcription factor.
    Reactive oxygen species in pulmonary hypertension: Reactive oxygen species may play important roles in the pathogenesis of pulmonary hypertension. We found that patients with pulmonary hypertension exhibited increased oxidative stress. Furthermore, mechanisms for pulmonary vascular smooth muscle cell growth have been shown to involve reactive oxygen species as signal transduction mediators. While the concept of reactive oxygen species being signaling mediators has been popular for the past 15 years, molecular targets of these species have not been defined. Our laboratory identified that signal transduction activators that are important for the development of pulmonary hypertension such as endothelin-1 and serotonin promote protein carbonylation. We are testing the hypothesis that protein carbonylation may play important roles as mechanistic targets of redox signaling.

    Shults NV, Kanovka SS, Ten Eyck JE, Rybka V, Suzuki YJ. Ultrastructural Changes of the Right Ventricular Myocytes in Pulmonary Arterial Hypertension. J Am Heart Assoc. 2019 Mar 5;8(5):e011227. doi: 10.1161/JAHA.118.011227.
   Rybka V, Suzuki YJ, Shults NV. Effects of Bcl-2/Bcl-xL Inhibitors on Pulmonary Artery Smooth Muscle Cells. Antioxidants. 2018 Oct 26;7(11). pii: E150. doi: 10.3390/antiox7110150.
   Shults NV, Melnyk O, Suzuki DI, Suzuki YJ. Redox Biology of Right-Sided Heart Failure. Antioxidants. 2018 Aug 8;7(8). pii: E106. doi: 10.3390/antiox7080106.
   Suzuki YJ, Shults NV. Redox Signaling in the Right Ventricle. Adv Exp Med Biol. 2017;967:315-323. doi: 10.1007/978-3-319-63245-2_19.
   Zungu-Edmondson M, Shults NV, Melnyk O, Suzuki YJ. Natural reversal of pulmonary vascular remodeling and right ventricular remodeling in SU5416/hypoxia-treated Sprague-Dawley rats. PLoS One. 2017 Aug 15;12(8):e0182551. doi: 10.1371/journal.pone.0182551.
   Ibrahim YF, Shults NV, Rybka V, Suzuki YJ. Docetaxel Reverses Pulmonary Vascular Remodeling by Decreasing Autophagy and Resolves Right Ventricular Fibrosis. J Pharmacol Exp Ther. 2017 Oct;363(1):20-34. doi: 10.1124/jpet.117.239921.
    Wang X, Shults NV, Suzuki YJ. Oxidative profiling of the failing right heart in rats with pulmonary hypertension. PLoS One. 2017;12:e0176887. doi: 10.1371/journal.pone.0176887.
   Zungu-Edmondson M, Suzuki YJ. Differential stress response mechanisms in right and left ventricles. J Rare Dis Res Treat. 2016;1:39-45.
   Suzuki YJ, Ibrahim YF, Shults NV. Apoptosis-based therapy to treat pulmonary arterial hypertension. J Rare Dis Res Treat. 2016;1:17-24.
   Wang X, Ibrahim YF, Das D, Zungu-Edmondson M, Shults NV, Suzuki YJ. Carfilzomib reverses pulmonary arterial hypertension. Cardiovasc Res. 2016;110:188-99. doi: 10.1093/cvr/cvw047.
   Zungu-Edmondson M, Shults NV, Wong CM, Suzuki YJ. Modulators of right ventricular apoptosis and contractility in a rat model of pulmonary hypertension. Cardiovasc Res. 2016;110:30-9. doi: 10.1093/cvr/cvw014.
   Ibrahim YF, Wong CM, Pavlickova L, Liu L, Trasar L, Bansal G, Suzuki YJ. Mechanism of the susceptibility of remodeled pulmonary vessels to drug-induced cell killing. J Am Heart Assoc 3:e000520, 2014
   Bansal G, Das D, Hsieh CY, Wang YH, Gilmore BA, Wong CM, Suzuki YJ. IL-22 activates oxidant signaling in pulmonary vascular smooth muscle cells. Cell Signal 25:2727-2733, 2013
   Suzuki YJ, Steinhorn RH, Gladwin MT. Antioxidant therapy for the treatment of pulmonary hypertension. Antioxid Redox Signal 18:1723-1726, 2013
   Wong CM, Bansal G, Pavlickova L, Marcocci L, Suzuki YJ. Reactive oxygen species and antioxidants in pulmonary hypertension. Antioxid Redox Signal 18:1789-1796, 2013
   Wong CM, Preston IR, Hill NS, Suzuki YJ. Iron chelation inhibits the development of pulmonary vascular remodeling. Free Radic Biol Med 53:1738-1747, 2012
  Park AM, Wong CM, Jelinkova L, Liu L, Nagase H, Suzuki YJ. Pulmonary hypertension-induced GATA4 activation in the right ventricle. Hypertension 56:1145-1151, 2010
   Wong CM, Cheema AK, Zhang L, Suzuki YJ. Protein carbonylation as a novel mechanism in redox signaling. Circ Res 102: 310-318, 2008
   Liu L, Marcocci L, Wong CM, Park AM, Suzuki YJ. Serotonin-mediated protein carbonylation in the right heart. Free Radic Biol Med 45:847-854, 2008
   Suzuki YJ, Nagase H, Wong CM, Kumar SV, Jain V, Park AM, Day RM. Regulation of Bcl-xL expression in lung vascular smooth muscle. Am J Respir Cell Mol Biol 36:678-687, 2007
   Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD, Meldrum DR, Dupuis J, Long CS, Rubin LJ, Smart FW, Suzuki YJ, Gladwin M, Denholm EM, Gail DB; National Heart, Lung, and Blood Institute Working Group on Cellular and Molecular Mechanisms of Right Heart Failure. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 114:1883-1891, 2006
   Day RM, Agyeman AS, Segel MJ, Chévere RD, Angelosanto JM, Suzuki YJ, Fanburg BL. Serotonin induces pulmonary artery smooth muscle cell migration. Biochem Pharmacol 71:386-397, 2006
   Preston IR, Tang G, Tilan JU, Hill NS, Suzuki YJ. Retinoids and pulmonary hypertension. Circulation 111:782-790, 2005
   Liu Y, Suzuki YJ, Day RM, Fanburg BL. Rho kinase-induced nuclear translocation of ERK1/ERK2 in smooth muscle cell mitogenesis caused by serotonin. Circ Res 95:579-586, 2004
   Suzuki YJ, Day RM, Tan CC, Sandven TH, Liang Q, Molkentin JD, Fanburg BL. Activation of GATA-4 by serotonin in pulmonary artery smooth muscle cells. J Biol Chem 278:17525-17531, 2003

                                        DC Area Consortium for Integrative Cardio-Pulmonary Biology
                Integrative Cardio-Pulmonary Biology Workshops See: http://www9.georgetown.edu/faculty/ys82/Oxygen.htm