Research Abstracts

Jane H. Brice, MD, MPH

Associate Professor, Department of Emergency Medicine
My research work lies in the prehospital phase of stroke. Having been a paramedic for a long time and now as the medical director for Orange County EMS, I am particularly interested in the ways 911 telecommunicators and EMS personnel recognize and treat stroke patients before they arrive at the hospital. In collaboration with Dr. Kelly Evenson, PhD, Dr. Wayne Rosamond PhD, and Dr. Tony Morris MD, PhD, we have developed a web-based stroke education tool for 911 telecommunicators and EMS personnel. We have also examined the tapes of 911 calls to determine the demographics of callers and the words they use in relaying information about stroke patients. We are currently testing the effectiveness of a stroke assessment tool for use by 911 telecommunicators during a 911 call to detect stroke at the earliest possible moment of a patient’s contact with the medical system.
Contact: brice@med.unc.edu

Ana C.G. Felix, MD

Assistant Professor, Neurology Department
Interests: Clinical stroke and prevention, clinical stroke outcomes, stroke registry, quality assurance in stroke care, young stroke, HIV and stroke, neurosonology. I am working on resubmitting a grant for an outcomes registry in the next 6 months.
felixa@neurology.unc.edu

Laurence Katz, MD

Research Associate: Jonathan Frank
Department of Emergency Medicine
Our group is interested in developing therapeutic interventions to reduce or reverse brain damage from cardiac arrest, stroke and head injury. We developed an outcome model of asphyxial cardiac arrest in rats to conduct translational research. The model simulates the pathophysiology of cardiac arrest with prolonged coma, persistent memory/learning deficits and ischemic neuronal cell death. Our stem cell work is conducted in collaboration with Dr. William Coleman. We are implanting adult liver stem cells (WB-F344) in the hippocampus after resuscitation from cardiac arrest. The goal of the research is to determine whether these cells will transdifferentiate into neurons, integrate into the brain’s architecture and restore brain function in regions damaged by cardiac arrest.
laurence_katz@med.unc.edu

Souvik Sen, MD, MS

Director of UNC Stroke Program, Associate Professor, Neurology Department. The UNC Stroke Program serves as the core for the multi-department comprehensive program and is located in the “Buckle of the Stroke Belt” and sees over 650 stroke/TIA patients annually. It includes 3 fellowship trained stroke faculty members, a 6-bed stroke unit, an acute stroke team, a stroke clinic, a stroke database manager and two full-time stroke coordinators. Neuroimaging is available including 3.0 and 1.5 T MR systems capable of DWI/PWI, and a 64-detector spiral CT with CTA and CT perfusion.UNC is the coordinating center for the CDC Stroke Registry. pharmaceutical companies. There are ongoing acute and stroke prevention trials (Phase I-IV). With this setup, the UNC Stroke program is able to provide one of the best in clinical care, research and education to patients in the state of North Carolina.

Dr. Sen’s research interests include acute stroke treatment and stroke prevention, clinical stroke outcomes, aortic arch atheroma and cardioembolic stroke. There are several ongoing research projects.
SenS@neurology.unc.edu

Alisa Wolberg, PhD

Assistant Professor, Department of Pathology and Laboratory Medicine
he focus of my lab is on the biochemistry of blood coagulation. Coagulation occurs after cellular proteins are exposed to flowing blood. Exposure of these proteins triggers a series of enzymatic reactions that culminate in the production of thrombin. Thrombin then cleaves the plasma protein, fibrinogen, to fibrin, which polymerizes into a web-like mesh that traps platelets and forms a blood clot. To examine events in blood coagulation pathways, we have developed an in vitro assay system that models blood coagulation in vivo. This system permits precise control of protein levels and cell and platelet numbers, granting exquisite control over experimental conditions. Using this system, we can correlate enzyme activity (thrombin) and functional effect (fibrin clot formation). This system has demonstrated its utility as an important preclinical tool in studies examining plasma components.

Our recent studies have focused on the ability of the coagulation response to modulate fibrinogen cleavage to fibrin and how this affects the stability of the resulting clot. We have observed that elevated levels of prothrombin, the nonenzymatic pro-enzyme form of thrombin, correlate with an altered fibrin clot structure. We hypothesize that this altered structure results in a "overly-stable" clot, which impairs the body's ability to appropriately clear the clot, and causes the thrombotic tendency in individuals with elevated prothrombin. We have also observed that deficiency in factor IX, a protein missing in patients with hemophilia B, also results in an altered clot structure. Clots formed in the absence of factor IX are weak and poorly formed, and have a decreased stability in the presence of fibrinolytic enzymes. We hypothesize that this decreased stability causes the bleeding tendency of hemophilic patients.

Currently, we are comparing two strategies currently used to treat hemophilic bleeding. Factor IX or factor VIII administration replaces missing factor IX or VIII. Alternately, rFVIIa (NovoSeven) or FEIBA (which contains activated procoagulant proteins) bypass the need for missing factor. Both therapies enhance thrombin generation in in vitro assays; however, their effects on fibrin clots are not known. We are also examining the ability of prothrombin to affect the hemophilic fibrin clot structure. Since increased levels of prothrombin produce clots with thinner fibrin fibers, differences in endogenous prothrombin levels may explain differences in the efficacy of NovoSeven when treating hemophilic bleeding. We are therefore using our cell-based model of coagulation to determine what dose level and pattern of NovoSeven administration leads to normalization of clot structure in models of hemophilia and elevated prothrombin.
alisa_wolberg@med.unc.edu