Suzuki Laboratory

Department of Pharmacology

Georgetown University Medical Center

 

See

 

http://gumc.georgetown.edu/news/203659.html

 

and

 

http://www.georgetown.edu/story/pulmonary-hypertension-gene-protein-function.html

 

for recently published stories about our laboratory.

 

 

Laboratory Mission:

To investigate signal transduction mechanisms for cardiac and smooth muscle cell regulation in order to develop therapeutic strategies against heart and lung diseases

 

 

Principal Investigator:

Yuichiro J. Suzuki, Ph.D.

Professor

 

Appointed Member, Respiratory Integrative Biology and Translational Research [RIBT] Study Section, NIH

 

Editorial Board Member, Antioxidants & Redox Signaling (www.liebertpub.com/ars) Impact factor 8.456

 

Editorial Board Member, Pulmonary Circulation (www.pulmonarycirculation.org )

 

Member, Program Committee, Pulmonary Circulation Assembly, American Thoracic Society

 

Council Member, Oxygen Club of Greater Washington DC

 

2006 President, Oxygen Club of Greater Washington DC

 

 

 

Suzuki Lab Members (2011-2012):

 

Lucia Marcocci, PhD

Visiting Professor from University of Rome

 

Geetanjali Bansal, PhD

Research Assistant Professor

 

Chi-Ming Wong, PhD

Research Assistant Professor

 

Yasmine Ibrahim, MD

Ph.D. Student

 

Makhosazane Zungu-Edmondson, PhD

Postdoctoral Fellow

 

Cheng-Ying Hsieh, PhD

Postdoctoral Fellow

 

Yi-Hsuan Wang

Research Assistant

 

Dividutta Das

Research Assistant

 

 

 

 

 

Ongoing Research:

 

Project 1:  Mechanism of redox signaling

 

Project 2:  Apoptosis-based therapy to reverse pulmonary vascular remodeling

 

Project 3:  Mechanisms of right ventricular hypertrophy and failure

 

 

Funding Sources:

 

NIH R01 HL72844  Mechanism of apoptosis in lung vascular smooth muscle

NIH R01 HL97514  Oxidant signaling for airway remodeling and inflammation

 

 

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.

 

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

 

Suzuki YJ, Forman HJ, Sevanian A. Oxidants as stimulator of signal transduction. Free Radic Biol Med 22: 269-285, 1997 [Cited 980 times]

 

 

Pulmonary Hypertension & 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.

 

Wong CM, Bansal G, Pavlickova L, Marcocci L, Suzuki YJ. Reactive oxygen species and antioxidants in pulmonary hypertension. Antioxid Redox Signal 2012 [Epub ahead of print]

 

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

 

 

Obstructive Sleep Apnea

 

Day RM, Matus IA, Suzuki YJ, Yeum KJ, Qin J, Park AM, Jain V, Kuru T, Tang G. Plasma levels of retinoids, carotenoids and tocopherols in patients with mild obstructive sleep apnoea. Respirology 14:1134-1142, 2009

 

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

 

 

 

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. 

 

Antioxidants (Pharmacology Elective for Medical Students)

   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)

 

Aria Hong, M.D.

Brent A. Gilmore, 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