Cerebral aneurysms are common vascular lesions seen in up to five percent of the population, that, when ruptured, can lead to catastrophic consequences with up to 50 percent mortality and morbidity. The cerebral aneurysm research lab aims to further the understanding of molecular pathways underlying cerebral aneurysm formation in order to induce repair and prevent rupture. Current research efforts are directed by resident Kamil W. Nowicki, MD, PhD, under the joint mentorship of Robert M. Friedlander, MD, and Bradley Gross, MD. Techniques and models used in the lab depend heavily on molecular cell biology, animal surgeries and biomedical engineering to study immune cell behavior in response to chemokines and their interactions with hemodynamic shear stress.
Current projects include:
Role of Platelets in Cerebral Aneurysm Formation and Healing
This project is actively exploring the role of platelets and inflammatory cytokines released by platelets in cerebral aneurysm formation. Current efforts are directed on using small molecule inhibitors in preventing aneurysm formation. This work resulted in a patent application PittID-05390 “Small molecule inhibitor therapy targeting platelet-CXCL7-CXCR1/2 axis to prevent aneurysm formation, growth, or rupture."
Role of Hemodynamic Shear Stress in Cerebral Aneurysm Formation
This study utilizes a novel in vitro model that simulates flow conditions within human aneurysms to induce inflammation and secretory chemokine response. In previous work, the authors showed that hemodynamic shear stress induces aneurysm formation via interleukin-8 and CXCL-1 mediated neutrophil inflammatory response. That work resulted in a patent application UFTINV-200015 T17844 “Drug therapy to prevent formation or enlargement or rupture of aneurysms." In a follow-up paper, they were able to show that this inflammatory response results in M1/M2 macrophage imbalance, driving aneurysm formation.
Biomarker Discovery and Platform Development
Future study that will focus on biomarker discovery to arrive at a blood test for cerebral aneurysm formation.
Novel Endovascular Therapeutic Agents
New ongoing collaboration with Seungil Kim, PhD, and William Wagner, PhD, from the University of Pittsburgh Department of Biomedical Engineering that is moving from in vitro to in vivo phase. This project is exploring novel pH-responsive embolic agents for endovascular treatment of cerebral aneurysms.