Engineering of supporting vasculature in addition to the implantation of the stem cells in the infracted myocardium represents a promising strategy for clinical applications of stem cell therapies for cardiovascular diseases. The overall goal of this study is to develop the technology to enhance the morphology and function of post-infarct neovasculature, prior to scar formation, and to establish the optimal time post-myocardial infarction (MI) when proangiogenic interventional strategies could result in maximal in situ renewal of myocardial tissue which has been lost to MI. The long term goal of our interdisciplinary group is to develop a novel technology to selectively target pharmaceutical agents to diseased tissue to rebuild the microenvironment in support of tissue regeneration.

Tissue exposed to ionizing radiation for therapeutic purposes is significantly altered. One of these alterations is the upregulation of several adhesion molecules (e.g. β3 chain, E-selectin) on the luminal surface of the endothelium in the tumor and the surrounding normal tissue. This radiation induced upregulated expression of tumor vasculature endothelial cell adhesion molecules provides a potential avenue for targeting drugs/genes to breast tumors. We have developed a novel approach in which, subsequent to radiotherapy, a ligand bearing drug carrier would be administered. The drug carrier would contain an antivascular agent and, on its outer surface, a recognition molecule (ligand) for a cognate molecule (receptor) that is expressed selectively (due to exposure to the radiation) on the luminal surface of the endothelium within the tumor.

Particle adhesion to vascular endothelium depends critically upon particle/cell property (size, receptors), scale/geometric features of vasculature (diameter, bifurcation etc.) and local hemodynamic factors (stress, torque etc.). Currently, this is investigated using in-vitro parallel-plate flow chambers which have several important limitations including (a) idealized, macrocirculatory scaling (b) lack of critical morphological features (junctions,network), healthy vs. diseased vasculature and (c) large volumes (several ml) and (d) contamination due to non-disposability. We are developing a comprehensive toolkit for studying cell/drug carrier adhesion to the vascular endothelium of normal and diseased tissue comprising of (a) microfluidic, microvascular network on a chip and (b) customized software to model cell-adhesion in these microfluidic chips.

Manned missions have become an integral component of space exploration. However, the impact of space radiation exposure on astronauts is not always predictable. Therefore, NASA has clearly identified a need for rapid, efficient and non-destructive detection and isolation of radiation damaged cells from human subjects. In collaboration with CFD Research Corp. (Huntsville, AL), we are developing a next generation, miniaturized (microfluidic) device for automated detection and sorting of radiation damaged cells during deep space flight.

Breast cancer is the most common cancer and second leading cause of cancer death in American women. Current treatments for breast cancer using intravenous chemotherapy often result in adverse systemic side effects, causing significant toxicities in healthy tissues. Cancer chemoresistance developed during chemotherapy treatments also reduces the treatment efficacy. A nanoparticle based targeted drug delivery system to selectively deliver anti-tumor agents are designed to overcome drug resistance and improve treatment efficacy.

Myocardial infarction is the leading cause of death in the United States. “Engineering” lost myocardium to prevent the appearance of chronic cardiac failure following MI is an attractive approach. Recent data have provided proof of principle that stem cell therapy is capable of restoring injured tissues; however, attempts at rebuilding the injured cardiac and other tissues using stem cells have yielded disappointing results. Development of a targeting system that can specifically deliver stem cells into the infarcted tissue would augment the rebuilding of the injured cardiac tissues. The goal of this project is to use this technology to improve the survival of stem cells, and further improve cardiac function.

A major goal in regenerative medicine is to provide blood supply for the repaired tissue. Recent evidence suggests that bone marrow derived mesenchymal stem cells can contribute to new blood vessel formation; however, the mechanisms that are governing the commitment of these cells into endothelial cells are poorly understood. We are trying to understand importance of the physical forces generated during flow through microvasculature on differentiation of these cells into endothelial cells. Understanding of the environmental signals that govern the fate of mesenchymal stem cells is essential for both basic biological insights and addressing the potential of these cells for cell based therapies.