Research Interests

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Research Interests

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Microvascular Network on a Chip

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 being 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, (c) large volumes (several mL) and (d) contamination due to non-disposability. We are designing 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.

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Regenerating Cardiac Tissue Through Targeted Drug Delivery

Engineering of supporting vasculature in addition to the implantation of stem cells in the infracted myocardium presents a promising strategy for clinical application of stem cell therapies for cardiovascular diseases. The overall objective of this study is to create 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 lost to MI. Our interdisciplinary group ultimately hopes to develop a revolutionary technology to selectively target pharmaceutical agents to diseased tissue to rebuild the microenvironment in support of tissue regeneration.

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Targeted Delivery of Antivascular Drugs to Irradiated Tumors

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 engineered an alternate approach in which, subsequent to radiation, 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.

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Microfluidic Device for Detecting Radiation Damage During Deep Space Flight

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 designing and creating a next generation, miniaturized (microfluidic) device for automated detection and sorting of radiation-damaged cells during deep space flight.

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Development of multidrug delivery system to overcome chemoresistance in breast cancer

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 novel nanoparticle-based targeted drug delivery system to selectively deliver anti-tumor agents is designed to overcome drug resistance and improve treatment efficacy. 

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Targeting stem cell to myocardial infarction heart in rats

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 the principle that stem cell therapy is capable of restoring injured tissues; but despite this newfound proof, 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 ultimate objective of this project is to use this technology to improve the survival of stem cells, and further improve cardiac function.   

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