Research and Scholarly Interests

• Vascular mechanobiology
• High-throughput assay development

Current Research

• Platelet storage for transfusion

Platelets are transfused to prevent bleeding and induce hemostasis, and can thus be critical in saving lives following trauma. Currently, platelets isolated from volunteers are stored at room temperature (RT) with gentle agitation for up to 5 days, before transfusion. This short shelf-life severely compromises platelet inventories and creates chronic shortages with the major issue being bacterial contamination. To address this issue, we are pursuing refrigerated platelets as a viable product for transfusion. We have shown that refrigerated platelets are superior to platelets stored at RT under standard blood-banking conditions by several metrics: metabolic and hemostatic functions, response to physiologic inhibitors, and clot mechanical properties. Our work, in collaboration with the U.S. Army, has recently prompted the FDA to clarify that cold-stored platelets may be used as a therapeutic product for active hemorrhage.

• High-throughput antimicrobial drug discovery and diagnostics

Infectious diseases are still the leading cause of death in the world as new organisms and drug resistance strains emerge. There is an urgent need for early detection and targeted treatment of the pathogens. To fill this technology gap, we have developed a miniaturized microbial culture platform that has cut down the time, cost, and reagent use. Our platform consists of several thousand spots of 3-dimensional, 30 nL cultures of single or multiple bacterial (Staphylococcus aureus, Pseudomonas aeruginosa) and fungal (Candida albicans) species grown on glass or paper substrates. We have shown that despite more than 3000-fold reduction in volume, our nano-scale cultures on the chip are comparable to current industry standards. We have used this screen to identify novel drugs and their combinations with effective antimicrobial activity. We have also modified this platform for a rapid and inexpensive point-of-care for testing drug efficacy.

• Role of fluid shear stresses and transport on inflammatory response

The focus of medicine has been on chemical factors as the chief determinant of disease development and treatment. Recently, we have come to recognize that physical factors such as mechanical forces can be just as important. We have investigated the role of fluid shear stresses and transport due to blood flow on infection and inflammation. Using in vitro microscale models of the blood vessels, we have shown that physiological levels of fluid shear stress can significantly upregulate pro-inflammatory responses from monocytes infected with Chlamydia pneumoniae, a pathogen implicated in atherosclerosis. In another study, we have shown that blood flow can monocytes assist in the adhesion of the otherwise non-adherent metastatic breast tumor cells to the microvascular endothelium under flow thus increasing the chances of hematogenous metastasis.

Recent Funding

1. Systems biology based tools for modeling platelet storage lesion for optimal blood transfusions (PI), DOD
   SBIR Phase II Subcontract, 10/01/2016-09/30/2018
2. The role of factor XIII on platelet contractility (PI)
   CCCRP, MRMC, US Army, 10/1/2016-09/30/2019
3. Interaction between fluid shear and Chlamydia pneumoniae infection in atherosclerosis (PI)
   SC1, NIH