https://www.youtube.com/channel/UCefN5Ae7XHZPDndSXP_XRUw
Washington DC, USA
Research Focus:
(1) Redox
Signaling
(2) Pulmonary
hypertension and right heart failure
Investigators:
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
Assistant Professor
Council Member, Oxygen Club of
Greater Washington DC
Lab Members:
Lucia Marcocci,
PhD
Visiting Associate Professor from
University of Rome
Vladyslava Rybka
Research Assistant
Current Support:
NIH R01 HL072844
NIH R21 AI142649
NIH R03 AG059554
NIH R03 AA026516
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, 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]
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.
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, Chˇvere 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
Educational
Activities:
DC
Area Consortium for Integrative Cardio-Pulmonary Biology
Integrative Cardio-Pulmonary Biology Workshops
See: http://www9.georgetown.edu/faculty/ys82/Oxygen.htm
Pulmonary
Diseases: Current Management and Novel Research Approaches (Pharmacology
Elective for Medical Students)
This elective will cover respiratory diseases
including asthma, chronic obstructive pulmonary disease (COPD), lung fibrosis,
pulmonary hypertension, and sleep apnea. (Some of these topics are not
covered anywhere else in the Pharmacology course.) The sessions will
include clinical case presentations focusing on pathogenic mechanisms,
therapeutic strategies and current research efforts to find new
treatments. Instructors include practicing pulmonologists and pulmonary
disease researchers.
The objective
of this session is to provide basic knowledge of antioxidants and oxygen free
radicals, which might help in advising patients and the general public about
taking
antioxidant supplements.
Antioxidants are molecules that can eliminate reactive oxygen
species, including free radicals. Molecular oxygen, which is needed for generating energy for our body, can also produce reactive oxygen species. These species have been shown to damage biological molecules and may cause diseases, but more recently, their roles as functional signaling molecules have been recognized. Commercially available antioxidants are advertised for health benefits including anti-aging, anti-cancer, improvement of skin, hair and memory, and the prevention of the common cold. Natural as well as synthetic antioxidants can attenuate oxidant-mediated damage, but could also alter the functional benefits of reactive oxygen. This Elective consists of lectures and discussions on the mechanisms and functions of reactive oxygen species and antioxidants.
Former Lab Members (Tufts
& Georgetown)
Oleksiy Melnyk
Sergey S. Kanovka
Jennifer Ten Eyck
Faisal Almonsour
Camilla Cucinotta
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