Overall Lab Objective
Our research focuses on cell adhesion and drug delivery. Specifically, we are utilizing the physiological and cellular response to inflammation and corresponding blood hemodynamics to design bio-functionalized particles for targeted drug delivery and imaging.
Dr. Alex Thompson
Alex’s research involves designing micro/nanoparticles of various size, shape, density and material for use as vascular-targeted drug carriers. By optimizing the physical parameters of these carriers to promote efficient adhesion to the endothelium, we can ultimately improve disease treatment by providing localized delivery of potent therapeutics and imaging agents specifically to diseased tissue via the circulation. To date, his research has shown that the interplay between particle parameters (such as size and shape) and blood flow hemodynamics plays a major role in the ability of particles to marginate (localize and adhere) to inflamed endothelium both in vitro and in vivo.
Dynamics in Blood Flow
Peter’s research investigates particle-blood cell dynamics in blood flow. Specifically, Peter is interested in whether inflammation targeted particles influence the inflammatory response of leukocytes to an inflamed endothelial monolayer and if leukocyte adhesion is effected by carrier design parameters (carrier size, shape, and targeted ligand density). Along with particle-blood cell dynamics, he also investigates the influence of surface-grafted poly(ethylene glycol) chains and the adhesion of targeted drug carriers in blood flow.
Hemodynamics and Comparative In-Vivo Study
Katawut’s research involves elucidating the potential role of hemodynamics and size and shape in prescribing the binding efficiency of vascular-targeted carriers in flow via microfluidic flow channel assays. Specifically, particles conjugated with sialyl Lewis-a , a ligand specific to the endothelial- expressed selectin, and with diameters ranging from 200 nm up to 5 mm were evaluated in a micro-chamber for their ability to effectively bind activated endothelial cells (aECs) in blood flow. Moreover, Kata also investigates the role of physical properties of carriers on the eventual in vivo binding efficiency to the vascular wall. Instead of mimicking physiological conditions, his experiments are done in animal model for comparison with in vitro study, which can allows extrapolation of in vivo prediction of particle binding to human.
Mathematical Modeling of Blood Flow
Dr. Mariana Carrasco-Teja
Dr. Carrasco-Teja's current research interests lie in the mathematical modeling of blood flow in the micro-scale. She's currently working on an algorithm to accurately represent the interaction between rigid micro and nano particles with blood cells in flow to mimic the behavior of VTCs of different shapes and sizes. She works in conjunction with Prof. Veerapaneni in the Department of Mathematics at the University of Michigan.
Interaction of Two Vesicles in Unbounded, Circular Flow
Plasma Protein Adsorption
Daniel’s current research is focused on the effect of plasma protein adsorption on adhesion of biodegradable vascular targeted carriers (VTCs) from human blood flow to inflamed endothelial cells. Plasma protein adsorption on intravenously injected drug carriers modulates their organ distribution and clearance from the bloodstream. However, the role of plasma protein in prescribing the adhesion of carriers to thevascular wall remains relatively unknown. Dan’s research looks at adhesion of vascular-targeted poly(lactide-co-glycolic-acid) (PLGA) particles in human blood flow and aims to understand the potential role that plasma proteins could play in this process. PLGA is a well-characterized and commonly proposed drug carrier and hence, FDA-approved. Overall, understanding how distinct plasma proteins modulate vascular-targeted carriers’ (such as PLGA) adhesion would allow for the design of highly functional delivery vehicles. Three main media Dan uses in his adhesion assays consist of buffer, plasma, and human blood and my results from these assays indicate that the effect of plasma proteins on adhesion of carriers is largely negative and a function of both particle material and human blood donor.
Margaret's research uses photo-initiated hydrogel fabrication techniques and investigates the effect of deformability of particles in complex blood flow. In addition, Margaret studies the particle fabrication, targeting, and margination of other biocompatible polymers.
Particle Interactions with White Cells
Dr. Cathy Fromen
Cathy is involved in numerous projects in the lab, with a focus on developing particle carriers directed against inflammation. She is currently investigating how realistic blood flow profiles influence white cell interactions with particles, and how particle properties can be altered to affect these interactions. She is also involved in particle fabrication and inflammation-related in vivo studies.