American Heart Walk Fundraising Dollars at Work
The American Heart Association is currently funding over $6 million to 44 active research studies at the University of Michigan. As one of the leading academic heart and vascular centers in the world, Frankel Cardiovascular Center researchers can assist the American Heart Association (AHA) in making strides in improving patient care, advocating for better health, reaching out to populations at risk, raising awareness, and protecting the future when it comes to cardiovascular health.
Through fundraising efforts like the annual Washtenaw County Heart Walk we continue to help fund important research studies like those you see below. Here we shine the spotlight on the AHA-funded researchers and their awards and projects.
Potential New Treatments for Blood Clotting Disorders
Jordan Shavit, MD, PhD
Assistant Professor of Pediatrics and Communicable Diseases
Funded Project: Identification of Novel Therapeutic Agents and Classes for Treatment of Venous Thromboembolism and Coagulopathy
AHA Award: $150,000 (1/2014-12/2015)
Dr. Shavit’s research is aimed at identifying new treatments for diseases caused by blood clotting complications, which include clots in the legs and lungs, as well as heart attack and stroke. Most cardiovascular disorders can be treated with several classes of oral medications, with up to ten medications per class. In contrast, there is currently a very limited repertoire of oral medications for the treatment of blood clotting disturbances. Many of the genetic factors underlying these disorders are unknown.
We are using zebrafish embryos to develop lead molecules that will be candidate medications for treatment of blood clotting disorders, and identify novel genes involved in these processes. This takes advantage of the ability to a screen a whole organism, enabling the identification of multiple classes of agents and genes that act on cells, molecules, or blood vessels. This may vastly expand the repertoire of medications and targets available for therapies, allowing us to significantly individualize treatments to the increasing numbers of patients with multiple medical problems.
RyR2 Mutation and Hypertrophic Cardiomyopathy
PhD Student, Molecular and Integrative Physiology
Funded Project: Mechanisms of Ryanodine Receptor Dysfunction in Cardiac Remodeling: Role of the Novel P1124L Mutation
AHA Award: $52,000 (7/2014-6/2016)
In this basic research project, PhD student Francisco Alvarado aims to understand the mechanisms by which alterations in the cardiac Ryanodine Receptor (RyR2) lead to heart disease. RyR2 is essential for heart function, but patients with genetic mutations affecting this protein suffer from Catecholaminergic
Polymorphic Ventricular Tachycardia. These patients have a normal heart structure and are seemingly healthy and live a normal life until a life-threatening cardiac arrhythmia occurs as a result of physical or emotional stress, potentially leading to sudden cardiac death.
Alvarado's research focuses on studying a new RyR2 mutation found in a patient with Hypertrophic Cardiomyopathy, a disease not only involving cardiac arrhythmias, but also severe thickening of the cardiac walls. This is the first RyR2 mutation associated with structural abnormalities of the heart. The objective is to determine the cellular, molecular and whole-organ mechanisms involved. To achieve this purpose, an innovative experimental design that takes advantage of a mouse model carrying the same mutation identified in the our patient is used, together with other state-of-the-art tools.
MAGUK Proteins and Arrhythmias
Justus M. Anumonwo, PhD
Assistant Professor, Department of Internal Medicine/Cardiovascular
Assistant Professor, Department of Molecular and Integrative Physiology
Funded Project: Arrhythmogenic Mechanisms in a Murine Model of Cardiac-Targeted Deletion of Sap97
AHA Award: $143,000 (7/2014-6/2016)
Ion channels are protein macromolecules responsible for generating an electrical event or ‘excitation,’ which underlies each heartbeat. Mutations in genes that encode these macromolecules, or proteins accessory to these macromolecules, can alter channel function, cause irregular heartbeats (arrhythmias), and may lead to fatality. ‘MAGUKs’ are a group of accessory proteins that direct normal assembly of ion channels in cell membranes, and thus regulate normal channel function. Dr. Anumonwo’s project examines molecular mechanisms by which mutations in MAGUK proteins may cause abnormal cardiac electrical rhythms.
This research, which is a collaborative effort with investigators at the Mayo Clinic (Rochester, MN), recently identified mutations in the archetypical MAGUK protein (SAP97) in a number of patients with irregular heartbeats. Our investigations use a multidisciplinary approach, including in vitro and in vivo experimental models, to determine the molecular mechanisms by which such identified SAP97 mutations may lead to abnormal electrical rhythms. Results of our investigations will provide important clues (a “therapeutic handle”) for treating the arrhythmias in such patients.
Development of a Novel ECPR Device
Robert W. Neumar, MD, PhD, FACEP
Professor and Chair, Department of Emergency Medicine
Funded Project: Optimizing Extracorporeal Cardiopulmonary Resuscitation (ECPR) for Refractory Cardiac Arrest
AHA Award: $139,472 (7/2015-6/2017)
Dr. Neumar’s basic science research has been focused on mechanisms of neuronal injury after ischemic and traumatic brain injury, as well as therapeutic strategies to improve neurologic outcomes including therapeutic hypothermia. His laboratory research focus has recently expanded to studies of ischemic post-conditioning in collaboration with Dr. Demetris Yannopoulos’ research team at the University of Minnesota, and studies of extracorporeal cardiopulmonary resuscitation (ECPR) in collaboration with Dr. Robert Bartlett’s research team in the ECLS Research Laboratory at U-M. Dr. Neumar is also
collaborating to develop a novel extracorporeal cardiopulmonary resuscitation (ECPR) device designed to provide goal-directed reperfusion using an automated closed-loop monitoring and control system.
A major focus of his laboratory has been to elucidate the role of calpains in post-ischemic neuronal death; they have also focused on optimizing post-cardiac arrest hypothermic targeted temperature management (HTTM). The major focus of Dr. Neumar’s clinical research is optimizing the management of post-cardiac arrest syndrome.