Professor, Graduate Programs in Bioscience
11301 Wilshire Blvd. 111E, Los Angeles, CA 90073Email:
Phone: (310) 268-3839
RESEARCH AND INTERESTS
My current research interest focuses on mechanobiology of cardiovascular diseases. Our group has demonstrated the first quantitative approach to changes in intravascular shear stress (ISS) with vascularoxidative stress in New Zealand White (NZW) rabbit and swine models. We have demonstrated that spatial (/x) and temporal (/t) variations in shear stress modulate post-translational oxidative modifications of low density lipoprotein protein (LDL) and mechano-signal transduction of mitochondrial redox states. These findings led to our first joint textbook for the field of mechanotransduction entitled “Hemodynamics & Mechanobiology of Endothelium”. By deploying micro-electromechanical systems (MEMS) sensors, we have demonstrated that the integration of ISS and electrochemical impedance spectroscopy (EIS) identifies pre-atherogenic lesions associated with oxidative stress in fat-fed NZW rabbits. We have further revealed that spatial (/x) and temporal (/t) variations in shear stress modulated oxidative stress of pro-inflammatory substrates; namely, oxidation of low density lipoprotein protein (LDL) and formation of macrophages/form cells. These findings led to the observation that oxidized lipids and macrophages caused distinct electrochemical properties in the vessel wall that can be measured by EIS. In this context, we are seeking to (1) characterize lipid-rich lesions via electrochemical impedance spectroscopy, (2) integrate shear stress (ISS), ultrasound (IVUS), and electrochemical impedance (EIS) for detection of lesions prone to rupture, and (3) determine the in vivo risk of rupture in high EIS plaque experienced high shear stress in a swine model.
Our laboratory has been inspired by the developmental biologists for their seminal contribution to
cardiovascular medicine using the zebrafish heart system. In collaboration with Dr. Ellen Lien (CHLA), Dr. Neil Chi (UCSD), and Dr. Shung (USC NIH Ultrasonic Transducer Resource Center), we have developed micro-ECG approached to assess electrical phenotypes in regenerating zebrafish hearts, and we have incorporated pulsed-wave Doppler to assess electromechanical coupling of myocardium in real-time. In collaboration with Dr. Chih-Ming Ho (UCLA), we are further developing time-dependent 3-D imaging (x, y, z, t) to elucidate the mechanotransduction mechanisms underlying cardiac
morphogenesis. Our joint efforts have demonstrated the use of zebrafish system formechanotransduction and electromechanical coupling in injured and regenerating hearts.
- Hwang, J., Ing, M., Salazar, A., Navab, M. Sevanian, A., Hsiai*, T. Pulsatile vs. oscillatory flow regulates NADPH Oxidase Subunit: Implication for Native LDL Oxidation. Circulation Research, 2003; 93:1225-1232.
- Takabe, W., Li, R., Yu F, Li A, Berliner, J., Hsiai* TK. Oxidized LDL-Activated JNK Regulates Mn-SOD Ubiquitination: Implication for Mitochondrial Redox Status and Apoptosis. Arteriosclerosis Thrombosis, and Vascular Biology. 2010;30:436-441.
- Ai L, Zhang L, Dai W, Shung KK, Hsiai*, TK.. Real-time Assessment of Flow Reversal in an Eccentric Arterial Stenotic Model. J Biomechanics 2010 Oct 19;43(14):2678-83.
- Takabe W, Jen N, Ai L, Hamilton R, Khalsa B, Darbandi F, Bressler S, Barr M, Li R, Hsiai* TK. Oscillatory Shear Stress Induces Mitochondrial Superoxide Production: Implication of NADPH Oxidase and c-Jun NH2-terminal Kinase Signaling. Antioxidants & Redox Signaling. 2011 Sep 1;15(5):1379-88 PMID: 20919940
- Fei Yu, Juhyun Lee, Nelson Jen, Xiang Li, Qiang Zhang, Rui Tang, Qifa Zhou, E.S. Kim, Tzung Hsiai*, Elevated Electrochemical Impedance in the Endoluminal Regions with High Shear Stress: Implication for Assessing Lipid-Rich Atherosclerotic Lesions. Biosensors and Bioelectronics. 2013 May 15;43:237-44. PMCID: PMC3594425
- Nelson Jen, Fei Yu, Steve Wusmund, Mohamed Hamden, Tzung Hsiai*. Atrial Fibrillation Pacing Decreases Intravascular Shear Stress in a New Zealand White Rabbit Model: Implications in Endothelial Function. Biomechanics and Modeling in Mechanobiology. 2013 Jun;12(4):735-745.
- Rongsong Li, Mohamad Navab, Zhi Ning, Payam Pakbin, Greg Hough, Kaveh Navab, Fei Yu, Nelson, Todd Morgan, Caleb Finch, Alan Fogelman, Constantinos Sioutas, Tzung Hsiai*. Ambient Ultrafine Particles Alter Lipid Metabolism and HDL Anti-Oxidant Capacity in LDLR-null Mice. Journal of Lipid Research. 2013 Jun;54(6):1608-15.
- Juhyun Lee, Mahdi Esmaily-Moghadam, Ethan Kung, Hung Cao, Tyler Beebe, Longhou Fang, Yuri Miller, Ching-Ling Lien, Neil C. Chi, Alison L. Marsden, and Tzung K. Hsiai*. Moving Domain Computational Fluid Dynamics to Interface with An Embryonic Zebrafish Model of Cardiac Morphogenesis. PLoS ONE 2013 Aug 23;8(8):e72924
- Hsiai T, Li S, Bursac N. Introduction to the Special Issue on Tissue Engineering and Regenerative Medicine. Ann Biomed Eng. 2014. Volume 42, Issue 7 (2014), Page 1355-1356.
- Cao H, Fei Yu, Yu Zhao, SCianmarello N, Lee J, Dai W, Jen N, Beebe T, Li R, Ebrahimi R, Chang DS, Mody FV, John Pacella, Yuchong Tai, Tzung Hsiai*. Stretchable Electrochemical Impedance Sensors for Intravascular Detection of Lipid-Rich Lesions in New Zealand White Rabbits. Biosensors and Bioelectronics. 2014 Apr 15;54:610-6.
- Michael Dickover, Jeffrey M. Hegarty, Kim Ly, Diana Lopez, Hongbo Yang, Ruilin Zhang, Neil Tedeschi, Tzung K. Hsiai, and Neil C. Chi. The atypical Rho GTPase, RhoU, regulates cell-adhesion molecules during cardiac morphogenesis. Developmental Biology. 2014 May 15;389(2):182-91.
- Hung Cao, Fei Yu, Yu Zhao, Joy Tai, Juhyun Lee, Ali Darehzereshki, Ellen C. Lien, Neil C. Chi, Yu-Chong Tai, Tzung K. Hsiai*. Wearable multi-channel microelectrode membranes to elucidate electrophysiological phenotypes of injured myocardium. Integrative Biology. 2014 Jun 19. [Epub ahead of print]
- Rongsong Li, Kaveh Navab, Greg Hough, Payam Pakbin, Eytan Wine, Jesus Araujo, Alan Fogelman, Constantinos Sioutas, Mohamed Navab, Tzung Hsiai*. Exposure to Atmospheric Ultrafine Particles Modulate Intestinal Lipid Peroxidation. Environmental Health Perspectives (in press)
- Hung Cao, Juhyun, Lee, Bong Kang, Nelson Jen, Kirk K. Shung, Tzung Hsiai*, Hemodynamics and Ventricular Function In a Zebrafish Model of Injury and Repair. Zebrafish (in press)
- Fei Yu, Wakako Takabe, Michael Harrison, Nelson Jen, Taylor Bebee, Juhyun Lee, Hung Cao, Peidong Han, Ching-Ling Lien, Rongsong Li, Neil C. Chi, Tzung K. Hsiai*. Shear Stress-Activated Wnt-Angiopoeitin-2 Signaling Recapitulates Vascular Development and Repair in Zebrafish Embryos. Arteriosclerosis Thrombosis, and Vascular Biology (in press)
- B.S., Columbia University
- M.D., University of Chicago
- Ph.D., UCLA, 2001
AWARDS AND RECOGNITION
- 2013-present Member, NIH Bioengineering, Technology and Surgical Sciences Study Section
- 2012 Zumberge Award for NIBIB T32 Training Grant Preparation at USC
- 2011 Viterbi School of Engineering Innovation Fund
- 2010-present Member, American Society for Clinical Investigation
- 2008 Member, Western Society for Clinical Investigation
- 2007 UCLA SEAS Distinguished Young Alumnus Award
- 2007 Zumberge Interdisciplinary Award for USC Cardiovascular Research Core
- 2006 Junior Faculty Research Award, School of Engineering, University of Southern California
- 2005 American Society of Clinical Investigation/Association of American Physicians Joint Meeting Award
- 2005 Fellow, American College of Cardiology
- 2004 Finalist, Irvine H. Page Young Investigator Research Award, American Heart Association
- 2003 Zumberge Research Award, University of Southern California
- 2002 National Institutes of Health, Career Development Award (K08 HL068689-01A1)
- 2002 John J. Sampson Outstanding Research Award, American Heart Association
- 2001 UCLA Chancellor’s Funds for Academic Border Crossing
- 2001 American Physiologic Society/Cardiovascular Section Young Investigator Award, Orlando, FL
- 2001 American College of Cardiology/Bristol-Myers Squibb Cardiology Fellow Award, Orlando, FL
- 1997 School of Engineering & Applied Sciences, UCLA, Johnson Memorial Scholarship
- 1996-2001 UCLA STAR Fellowship: NIH NRSA (HL07895)
- 1994 Finalist, American College of Physicians, Atlanta, GA
- 1989-93 University of Chicago Pritzker School of Medicine Medical Student Scholarship
- 1989 Columbia University President’s Award for Community Services
- 1989 American Chapter of Chemical Engineering and Tau Beta Pi
- 1984 Faculty Scholar, Arts and Sciences, University of Toronto, Ontario, Canada