Srivastava Research
1020 Locust Street
Jefferson Alumni Hall, Suite 394A
Philadelphia, PA 19107
Dr. Srivastava leads a multidisciplinary research team focused on investigating the pathophysiological and therapeutic roles of extracellular vesicles (EVs) in traumatic and neurological disorders. His research emphasizes the role of EVs as therapeutic agents, particularly in mitigating neuroinflammation and restoring endothelial function. By integrating fundamental biology with clinically relevant applications, his work aims to advance novel therapeutic strategies for conditions where conventional treatments fall short.
Research Projects
Extracellular Vesicles to Restore Neurovascular Integrity in ALS
ALS is a severe neurological disease-causing neuron death in the brain and spinal cord. Primarily affecting people over 55, it's more common in military veterans and those with prior brain injuries or infections. Early symptoms include muscle weakness or stiffness, leading to the loss of voluntary muscle movement for basic functions like chewing, walking, talking, and breathing. Unfortunately, ALS patients usually die from respiratory failure within five years of diagnosis, and no effective treatments exist to halt its progression. Recent findings reveal that the barrier between circulating blood and the nervous system breaks down early in the disease, even before neuron death. This barrier is made up of semipermeable endothelial cells, which prevent solutes from entering the nervous system where neurons are located. Our research shows that EVs from various cells can improve the function of this barrier. In our project, we are testing the therapeutic potential of EVs in animal ALS models to assess their ability to reduce neuron death and slow the disease's progression by repairing the damaged blood-nervous system barrier. If successful, this study could pave the way for future clinical trials, aiming to enhance the quality of life for ALS patients and potentially extend their survival.
Funding Support: The US Department of Defense (Award # HT94252310138)
Platelet-Derived Extracellular Vesicles for Hemorrhage Control & Prevention of Hemorrhagic Shock
Severe hemorrhage is a leading cause of death in combat military personnel. Recent research shows that early transfusion of platelets improves survival in severely injured patients. However, using platelets in austere environments has limitations due to shelf life and storage issues. Platelet-derived extracellular vesicles (PEVs) offer a promising alternative. They are stable, even after freeze-thaw cycles, and can be lyophilized, overcoming logistical barriers. Our data suggests that PEVs play a critical role in supporting hemostasis and preventing trauma-induced coagulopathy. Further studies show that PEVs can control bleeding, prevent hemorrhagic shock, and protect endothelial barriers. This project aims to evaluate PEVs' effects in acute hemorrhage control, prevention of multiple organ dysfunction, and modulation of endothelial function.
Funding Support: The US Department of Defense (Award # W81XWH2110682)
Therapeutic Potential of Mesenchymal Stromal Cell-derived Extracellular Vesicles in Ischemic Stroke
Ischemic stroke is a major cause of disability and death worldwide, and current reperfusion therapies often leave patients with lifelong disabilities. To address this, we need effective treatments for the ischemia/reperfusion (I/R) injury that follows a stroke. Unfortunately, there are no approved therapies for this, emphasizing the need for new approaches. Mesenchymal stem cells (MSCs) have shown promise for their therapeutic effects, mainly due to their paracrine activity. Excitingly, recent studies, including our own, have highlighted the potential of EVs secreted by MSCs (MSC-EVs) as a critical therapeutic factor. In this international collaborative project, we aim to explore the therapeutic potential of MSCs and MSC-EVs in treating ischemic stroke. Additionally, we intend to uncover the molecular mechanisms underlying their beneficial effects and identify circulating biomarkers that can predict functional outcomes. This research could lead to significant advancements in reducing the burden of ischemic stroke and related conditions.
Funding Support: Vickie and Jack Farber Foundation