Sascha N. Goonewardena, M.D.
Assistant Professor of Medicine, Cardiology, Medical School
B.S. in Biology and Philosophy, University of Michigan, 5/1999
M.D., University of Michigan Medical Schoo,l 6/2003
Resident Physician, University of Chicago Hospitals, Internal Medicine (2003-2006)
Postdoctoral Fellow, University of Chicago, Cardiology Department (2006-2007)
Cardiology Fellow, Division of Cardiovascular Medicine, University of Michigan Health System, 2006 - 2012
Postdoctoral Research Fellow in MNIMBS, 2009- 2012:
Cardiovascular disease – Dendrimer Nanomedicine
Sascha Goonewardena, M.D. has done two years research in the MNIMBS
nanomedicine program as part of his specialization in Cardiovascular Medicine. He is still embedded in the MNIMBS lab that supports his research efforts.
On December 13, 2010, Dr. Goonewardena was awarded $50,000 by the CVC Inaugural Grant fund for his proposal titled: Molecular imaging of inflammatory macrophages in vascular disease using a nanoparticle platform. The goal is to use folate targeted dendrimer nanodevices to gain fundamental insights into the pathophysiology and role of inflammatory macrophages in vascular diseases such as aortic aneurysm and atherosclerosis.
Cardiovascular disease remains the leading cause of death worldwide. During the last few decades, major advancements have been made in treating several forms of cardiovascular disease. From angioplasty to statin therapies, treatments have reduced the morbidity and mortality associated with cardiovascular disease. However, further advances have been hindered by systemic toxicities coupled with a limited understanding of the molecular mechanisms that mediate these disease processes.
The field of dendrimer-based nanomedicine has evolved rapidly over the last decade. Dendrimer molecules can perform several simultaneous functions, including targeted delivery of specific therapeutics and molecules, real-time visualization of dynamic homeostatic mechanisms, and in vivo sensing of diverse cellular processes. The multifunctional properties of dendrimer molecules coupled with their nano-scale proportions allow for targeted delivery and molecular monitoring with the specificity and biocompatibility enjoyed by endogenous substances. These technologies have the potential to overcome traditional barriers that currently limit our ability to understand, diagnose, and treat cardiovascular disease.
As our understanding of cardiovascular diseases has advanced, it has been recognized that much of the pathology stems from vascular dysfunction – both as an indirect facilitator and a direct mediator. Because of the central role of the vascular system in cardiovascular disease process, an understanding and an ability to monitor and leverage the molecular mechanisms of angiogenesis would prove beneficial in studying and treating cardiovascular disease processes.
Integrin adhesion molecules play a critical role in regulating cell-cell interactions and endothelial function, especially with regards to angiogenesis. Specifically, αvβ3 integrin is found on the luminal surface of endothelial cells during angiogenesis. Polyamidine (PAMAM) dendrimers with the Arg-Gly Asp(RGD) motif that binds to the αvβ3 integrin provide us with the ability to monitor dynamically and target pathological processes that involve angiogenesis. By using this and other PAMAM dendrimer constructs, we hope to further our understanding of cardiovascular diseases like atherosclerosis, heart failure, and myocardial infarction and hope to deliver targeted therapies in an efficient manner while simultaneously minimizing systemic toxicities that characterize current therapeutics.
Gerard Summer Fellowship, NSF Developmental Neurobiology Grant, Class Honors, Golden Key Honor Society, T-32 Training Grant (2009-present)
CVC inaugural grant award (2010).
Cardiac Papillary Fibroelastoma—A Volatile Variant. Sascha Goonewardena, M.D., Lissa Sugeng, M.D., James K. Min, M.D., and Roberto Lang, M.D. Clinical Echocardiography 2005. 1540-8175. doi.wiley.com/10.1111/j
Bioprosthetic Valve Thrombosis. Goonewardena SN, Shah DP, Sugeng L, Lang RM. Echocardiography. 2006 Jan;23(1):75-6. PMID: 16412191.
Fibrosing Cholestatic Hepatitis. Goonewardena S and Ross A. Clinical Vignette—Hepatology 2005.
Dual triggering improves the accuracy of left ventricular volume measurements by contrast-enhanced real-time 3-dimensional echocardiography. Caiani EG, Coon P, Corsi C, Goonewardena S, Bardo D, Rafter P, Sugeng L, Mor-Avi V, Lang RM J Am Soc Echocardiogr. 2005 Dec;18 (12):1292-8. PMID: 16376757.
Rapid online quantification of left ventricular volume from real-time three-dimensional echocardiographic data. Jacobs LD, Salgo IS, Goonewardena S, Weinert L, Coon P, Bardo D, Gerard O, Allain P, Zamorano JL, de Isla LP, Mor-Avi V, Lang RM. Eur Heart J. 2006 Feb;27(4):460-8. Epub 2005 Nov 30.PMID: 16319085
Images in Cardiovascular Medicine. Takotsubo Cardiomyopathy. Shah DP, Sugeng L, Goonewardena SN, Coon P, Lang RM. Circulation. 2006 May 16;113(19):e762. PMID: 16702478.
Quantification of regional left ventricular wall motion from real-time 3-dimensional echocardiography in patients with poor acoustic windows: effects of contrast enhancement tested against cardiac magnetic resonance. Corsi C, Coon P, Goonewardena S, Weinert L, Sugeng L, Polonsky TS, Veronesi F, Caiani EG, Lamberti C, Bardo D, Lang RM, Mor-Avi V. J Am Soc Echocardiogr. 2006 Jul;19(7):886-93. PMID: 16824998
Handcarried ultrasound measurement of the inferior vena cava for assessment of intravascular volume status in the outpatient hemodialysis clinic. Brennan JM, Ronan A, Goonewardena S, Blair JE, Hammes M, Shah D, Vasaiwala S, Kirkpatrick JN, Spencer KT. Clin J Am Soc Nephrol. 2006 Jul;1(4):749-53. Epub 2006 May 24. PMID: 17699282.
Comparison of the frequency of abnormal cardiac findings by echocardiography in patients with and without peripheral arterial disease. Ward RP, Goonewardena SN, Lammertin G, Lang RM. Am J Cardiol. 2007 Feb 15;99(4):499-503. Epub 2006 Dec 28.PMID: 17293193
Radial artery pulse pressure variation correlates with brachial artery peak velocity variation in ventilated subjects when measured by internal medicine residents using hand-carried ultrasound devices.
Brennan JM, Blair JE, Hampole C, Goonewardena S, Vasaiwala S, Shah D, Spencer KT, Schmidt GA. Chest. 2007 May;131(5):1301-7.PMID: 17494781
A comparison by medicine residents of physical examination versus hand-carried ultrasound for estimation of right atrial pressure. Brennan JM, Blair JE, Goonewardena S, Ronan A, Shah D, Vasaiwala S, Brooks E, Levy A, Kirkpatrick JN, Spencer KT. Am J Cardiol. 2007 Jun 1;99(11):1614-6. Epub 2007 Apr 18.PMID: 17531592
Reappraisal of the use of inferior vena cava for estimating right atrial pressure.
Brennan JM, Blair JE, Goonewardena S, Ronan A, Shah D, Vasaiwala S, Kirkpatrick JN, Spencer KT. J Am Soc Echocardiogr. 2007 Jul;20(7):857-61.PMID: 17617312
Value of vasodilator stress myocardial contrast echocardiography and magnetic resonance imaging for the differential diagnosis of ischemic versus nonischemic cardiomyopathy. Mor-Avi V, Koch R, Holper EM, Goonewardena S, Coon PD, Min JK, Fedson S, Ward RP, Lang RM. J Am Soc Echocardiogr. 2008 May;21(5):425-32. Epub 2008 Jan 9.PMID: 18187290
Use of Hand Carried Ultrasound, B-type Natriuretic Peptide, and Clinical Assessment in Identifying Abnormal Left Ventricular Filling Pressures in Patients Referred for Right Heart Catheterization. Sascha N. Goonewardena, John E. A. Blair, Amin Manuchehry, Michael Keller, Ryan Reeves, Adam Price, J. Matthew Brennan, Kirk T. Spencer, Jyothy Puthumana, Mihai Gheorghiade. Submitted Journal of Cardiac Failure, 2009; Vol. xx, Number yy; Pages zz-zz; doi:10.1016/j.cardfail.2009.08.004
Murine lung responses to ambient particulate matter: genomic analysis and influence on airway hyperresponsiveness. Wang T, Moreno-Vinasco L, Huang Y, Lang GD, Linares JD, Goonewardena SN, Grabavoy A, Samet JM, Geyh AS, Breysse PN, Lussier YA, Natarajan V, Garcia JG. Environ Health Perspect. 2008 Nov;116(11):1500-8. Epub 2008 Jun 20.PMCID: PMC2592270
Usefulness of hand-carried ultrasound to predict elevated left ventricular filling pressure. Blair JE, Brennan JM, Goonewardena SN, Shah D, Vasaiwala S, Spencer KT.
Am J Cardiol. 2009 Jan 15;103(2):246-7. Epub 2008 Oct 30.PMID: 19121445
Particulate Matter Exacerbates Respiratory and Cardiac Arrhythmias in Cardiomyopathic Mice via Heightened Carotid Body Sensitivity. Joe G.N. Garcia, Gabriel Lang, Liliana Moreno-Vinasco, Ting Wang, Yong Huang, Sascha N. Goonewardena, Ying-Jie Peng, Eric Svenson, Viswanathan Natarajan, Roberto Lang John Beshai, Jered Linares, Patrick Breysse, Alison Geyh, Jonathan Samet, Yves Lussier, Nanduri Prabhakar. Submitted Journal of Clinical Investigation 2010.
Targeting of inflammatory macrophages using a dendrimer-folic acid-methotrexate nanoparticle in a model of inflammatory arthritis. Thommey P. Thomas, Sascha N. Goonewardena, Istvan Majoros, Seok-Ki Choi, Alina Kotlyar, Zhengyi Cao , Pascale Leroueil, James R. Baker, Jr. Submitted to Arthritis and Rheumatism 2010.
BOOK CHAPTERS and REVIEWS
Goonewardena, SN. Non-invasive Assessment of Cardiac Output. Just The Facts: Critical Care. Hall, J.B., Hogarth, D.K., Schmidt, G.A. (editors) 2005.
Avrum Jacobs MD, Lynn C. Weinert RDCS, Sascha Goonewardena MD, Mardi Gomberg-Maitland MD MSc, Roberto M. Lang MD. Two-Dimensional and Three-Dimensional Transthoracic Echocardiography to Evaluate Cor Triatriatum in the Adult. Clinical Echocardiography, 2005.
Handcarried Echocardiography to Assess Hemodynamics in Acute Decompensated Heart Failure. Goonewardena SN, Spencer KT. Curr Heart Fail Rep. 2010 Oct 2. PMID: 20890689.
Metabolomics and atherosclerosis. Goonewardena SN, Prevette LE, Desai AA. Curr Atheroscler Rep. 2010 Jul;12(4):267-72. Review. PMID: 20464531.
Lisa E. Prevette, Ph.D.
Bachelor of Arts
Chemistry and Mathematics
Transylvania University in Lexington, KY 2001
University of Cincinnati 2008
Postdoctoral Fellowship, Department of Chemistry and MNIMBS 2008-2010
University of St. Thomas · Minnesota
Saint Paul, Minnesota 2010 -
Lisa Prevette, Ph.D. graduated from Transylvania University in Lexington, KY in 2001 with B.A. degrees in Chemistry and Mathematics. After a year with Eli Lilly, she returned to academia to pursue her Ph.D in Chemistry at the University of Cincinnati under the guidance of Professor Theresa M. Reineke studying the mechanisms of interaction between polymers and nucleic acids. Earning her doctorate in 2008, Lisa is now a Michigan Chemistry Fellow working with the Banaszak Holl group in collaboration with many distinguished researchers in MNIMBS nanomedicine program, and Professors Ramamoorthy and Al-Hashimi on determining the structure and dynamics of polymer-DNA complexes and their interactions with cell membranes using nuclear magnetic resonance spectroscopy. CV
Dr. Prevette's research at the
University of St. Thomas - Minnesota is in the area of biophysical chemistry, studying the interactions between biomaterials and biomolecules. In particular, we are interested in interactions that occur at the cell surface, leading to cellular internalization of drugs and genes for gene therapy. Students in the group learn about binding mechanisms, thermodynamics and kinetics, and the structure of biomolecules and their complexes.
Honors and Awards
Vaughan Symposium Poster Presentation Award University of Michigan, Aug 2009
Michigan Chemistry Fellows Postdoctoral Fellowship, November 2007
National Research Council Postdoctoral Fellowship - declined October 2007
Harry B. Mark Research Award University of Cincinnati, May 2007
University Research Council Summer Fellowship University of Cincinnati, May 2007
Hillstrom Travel Award University of Cincinnati, May 2007
Procter & Gamble Research Fellowship, May 2006
Outstanding Poster Presentation UC Graduate Poster Forum, March 2006
Most Interesting Scientific Presentation BioOhio Poster Competition, October 2005
Henry Hochstetter Award for teaching excellence University of Cincinnati, May 2004
William T. Young Distinguished Scholar Transylvania University, 1997-2001.
One of 25 full scholarships awarded to outstanding students
Omicron Delta Kappa Leadership Honorary Transylvania University, 2000
Prevette, L.E.; Mullen, D.G.; Banaszak Holl, M.M. “Polycation-induced Cell Membrane Permeability Does Not Enhance Cellular Uptake or Transfection Efficiency.” Biomacromolecules 2009 (submitted)
Prevette, L.E.; Lynch, M. L.; Reineke, T.M. “Amide Spacing Influences pDNA Binding of Poly(amidoamine)s.” Biomacromolecules, 2009 (accepted)
Prevette, L.E.; Mills, M.; Ramamoorthy, A.; Orr, B.G,; Andricioaei, I.; Banaszak Holl, M.M. “Structural Characterization of DNA-PAMAM Dendrimer Complexes.” ACS PMSE Preprints, 2008, 99, 795-796.
Prevette, L.E.; Kizjakina, K.; Lynch, M.L; Reineke, T.M. “Correlation of Amine Number and pDNA Binding Mechanism for Trehalose-based Polycations.” Langmuir 2008, 24, 8090-8101.
Prevette, L.E.; Lynch, M.L.; Reineke, T.M. “Understanding DNA Binding Mechanisms of Trehalose-Based Polycationic Gene Delivery Vectors.” ACS PMSE Preprints, 2007, 96, 843-844.
Prevette, L.E.; Kodger, T.E.; Reineke, T.M.; Lynch, M. L. “Deciphering the Role of Hydrogen Bonding in Enhancing pDNA-Polycation Interactions.” Langmuir 2007, 23, 9773-9784.
Srinivasachari, S.; Liu, Y.; Prevette, L.E.; Reineke, T.M. “Effects of Trehalose Click Polymer Length on pDNA Complex Stability and Delivery Efficacy.” Biomaterials 2007, 28, 2885-2898.
Srinivasachari, S.; Liu, Y.; Zhang, G.; Prevette, L.E.; Reineke, T.M. “Trehalose Click Polymers Inhibit Nanoparticle Aggregation and Promote pDNA Delivery in Serum.” J. Am. Chem. Soc. 2006, 128, 8176-8184.
Prevette, L.E.; Lynch, M.; Reineke, T.M. “Deciphering the Mechanism of Poly(glycoamidoamine)-DNA Interactions.” ACS PMSE Preprints, 2006, 94, 356-357.
Lee, C-C.; Prevette, L.E.; Lynch, M.; Reineke, T.M. “Synthesis and Physical Characterization of Novel Biodegradable Polyesters for Nucleic Acid Delivery.” ACS Polymer Preprints, 2005, 46, 335.
Joseph M Wallace, Ph.D.
Bachelor of Science and Engineering
Georgia Tech, 2002
Master of Science and Engineering
Ph.D. Biomedical Engineering
University of Michigan
Postdoctoral Fellow, Department of Chemistry and MNIMBS
Instructor Rackham Certificate Program in NanoBiology Seminar
Assistant Professor in the Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis
Joey Wallace, Ph.D. graduated with a BSE in Aerospace Engineering from Georgia Tech in 2002 before pursuing an MSE and Ph.D. in Biomedical Engineering from the University of Michigan. His Ph.D. work focused on mechanical and genetic influences on skeletal structure and function. He is currently a postdoctoral fellow in the Department of Chemistry and is studying the internalization and trafficking of polycationic polymer-DNA polyplexes in cells using AFM and confocal microscopy as part of the MNIMBS
nanomedicine program. Beginning in September, he will begin using AFM to study ultrastructural changes in bone and connective tissues of mice afflicted with Osteogenesis Imperfecta. Dr. Wallace serves as the Instructor of the Rackham Certificate in NanoBiology Seminar. See also: the current Seminar course web site.
Dr. Joey Wallace is
now Assistant Professor in the Department of Biomedical Engineering at IUPUI (Indiana University-Purdue University Indianapolis). His teaching responsibilities are primarily in the area of biomechanics. His primary research interests focus on understanding how biological and environmental factors influence the organization and assembly of bone. He has 3 main research goals: 1) Investigating hierarchical mechanisms of disease in mineralized tissues 2) Studying Age-related effects of mechanical loading on the bone extracellular matrix, and its relation to life-long fracture risk 3) Understanding nanoscale mechanisms of de novo tissue formation. Overall, by studying these systems, the goal of this work is to translate findings into rational and clinically-relevant diagnostic and treatment options for defects, damage and disease of musculoskeletal tissues.
1F32DE018840-01 A1 09/01/2008-09/01-2010
Title: Investigating Ultrastructural Collagen Changes in Osteogenesis Imperfecta
Role: Principal Investigator
The University of Michigan – Rackham Graduate School – February 2008
Nominated for Distinguished Dissertation Award
Ninth International Conference on the Chemistry and Biology of Mineralized Tissues – November 2007; New Investigator Award
The Sixth Annual Meeting of the Midwest Tissue Engineering Consortium – April 2007
Award for best judged poster presentation
The Dominic D. Dziewiatkowsi Award - The University of Michigan School of Dentistry – April 2007; Given in recognition of excellence in student research
The University of Michigan Engineering Graduate Student Symposium – November 2006
Best Oral Presentation, Biomechanics Concentration
Regenerative Sciences Training Grant R90-DK071506 - October 2004 to October 2006
Finney WF, Morris MD, Wallace JM, Kohn DH, “Ultrastructural Elastic Deformation of Cortical Bone Tissue Probed by NIR Raman Spectroscopy.” In: Proceedings of SPIE 2004; 5321: 233-241.
Morris MD, Finney WF, Callender A, Wallace JM, Kohn DH, “Chemical Structure Changes Accompanying Mechanical Loading of Cortical Bone Tissue.” In: Proceedings of the Eighth International Conference on the Chemistry and Biology of Mineralized Tissues, 2005, WJ Landis and J Sodek, Editors; University of Toronto Press, Toronto, Canada: 227-229.
Wallace JM, Rajachar RM, Chen XD, Shi S, Allen MR, Bloomfield SA, Les CM, Robey PG, Young MF, Kohn DH, “The Mechanical Phenotype of Biglycan Deficient Mice is Bone- and Gender-Specific,” Bone 2006; 39 (1): 106-116.
Wallace JM, Rajachar RM, Allen MR, Bloomfield SA, Robey PG, Young MF, Kohn DH, “Exercise-Induced Changes in the Cortical Bone of Growing Mice are Bone and Gender Specific,” Bone 2007; 40 (4): 1120-1127.
Kohn DH, Sahar ND, Wallace JM, Golcuk K, Morris MD, “Exercise Alters Mineral and Matrix Composition in the Absence of Adding New Bone,” Cells, Tissues, Organs 2009; 189: 33-37.
Hong SI, Hong SK, Wallace JM, Kohn D, “Ultrastructural Observation and Electron Irradiation Damage of Lamellar Bone,” Journal of Materials Sciences: Materials in Medicine 2009; 20: 959-965.
Wallace JM, Golcuk K, Morris MD, Kohn DH, “Inbred Strain-Specific Response to Biglycan Deficiency in the Cortical Bone of C57BL6/129 and C3H/He Mice,” JBMR, In Press, November 2008.
Wallace JM, Ron MS, Kohn DH, “Short-term exercise in mice increases tibial post-yield mechanical properties while two weeks of latency following exercise increases tissue-level strength,” Calcif. Tis Int., In Press, February 2009; DOI 10.1007/s00223-009-9228-8.
Hansma P, Yu H, Schultz D, Rodriguez A, Yurtsev E, Peters MC, Miller J, Wallace JM, Kang I, Kohn D, Buckley J, Weaver V, Lotz J, “Tissue Diagnostic Instrument,”Review of Scientific Instruments, March 2009.
Wallace JM, Golcuk K, Morris MD, Kohn DH, “Exercise Modulates the Phenotype of Biglycan-Deficient Mice in an Inbred Strain-Specific Manner by Altering Bone Composition and Mechanical Integrity,” Bone, Submitted, December 2008.
Stoichiometry and Structure of Poly(amidoamine) Dendrimer-Lipid Complexes
C. V. Kelly, M. G. Liroff, L. D. Triplett, P. R. Leroueil, D. G. Mullen, J. M. Wallace, S. Meschinchi, J. R. Baker, B. G. Orr, M. M. Banaszak Holl ACS Nano 2009 3, 1886-1896.
Whitney A. Dunlap, MD MS
Fellow, Allergy and Clinical Immunology and MNIMBS
University of Michigan
B.A. in History, University of Florida
M.S. in Biomedical Science, Eastern VirginiaMedicalSchool
M.D., Eastern VirginiaMedicalSchool
Internship and Residency in Pediatrics, BrownUniversity
During medical school and residency, Dr. Whitney Dunlap had the privilege of working for two nonprofit international health care organizations in Sub-Saharan Africa. Both organizations emphasized education of in-country healthcare providers in addition to treatment of patients. As a result, she developed an interest in healthcare delivery in the developing world and learned how efficient and pragmatic solutions can erode complex challenges. She is currently a fellow in the University of Michigan Division of Allergy and Clinical Immunology, and is developing a nanoemulsion-based intranasal pneumococcal vaccine. pneumococcus is a bacterial pathogen responsible for significant mortality worldwide. She hopes her work with MNIMBS will result in a more accessible vaccine that provides maximum immunity while eliminating the need for needle administration and cold chain storage.
6/2008 Brown Medical School Student Award for Recognition of Outstanding Teaching
5/2002- 8/2002 Physicians For Peace: Gwaltney International Fellow
8/1996- 5/2000 University of Florida:
Florida Academic Scholar
President’s Honor Roll
Phi Alpha Theta History Honor Society
10/22/1009 S. pneumoniae Vaccine Proof of Concept
Gates Foundation Grand Challenges in Global Health Annual Meeting
7/26/2009 A Novel Streptococcus pneumoniae Vaccine
John M. Sheldon Allergy Society, Tri-Annual Meeting
Ann Arbor, MI
11/2009 Dunlap W and Baldwin JL. A 34-year-old Female with Cryoglobulinemia Presenting with an Increasing IgM Following IVIG Infusion for Suspected CVID.
American College of Allergy, Asthma and Immunology 2009 Annual Scientific Meeting
8/2008 Dunlap W, Sanders G, and Baldwin JL. Allergic reaction to carmine in a pediatric patient after consumption of a popular fruit drink with a non-FDA approved carmine designation.
American College of Allergy, Asthma and Immunology
2008 Annual Scientific Meeting