Lisa E. Prevette, Ph.D. Fellow, Department of Chemistry and M-NIMBS

Lisa 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 M-NIMBS 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.

Joseph M Wallace, Ph.D.

Postdoctoral Fellow, Department of Chemistry and M-NIMBS

Joey 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.  Beginning in September, he will begin using AFM to study ultrastructural changes in bone and connective tissues of mice afflicted with Osteogenesis Imperfecta.

Sascha N. Goonewardena, M.D.

Cardiology Fellow

Division of Cardiovascular Medicine

University of Michigan Health System

Cardiovascular disease – Dendrimer Nanomedicine

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.