The following departmental faculty were awarded competitive and non-competitive research grants during calendar year 2013.
Zhen-Zhong Xu, PhD, of the Sensory Plasticity and Pain Research Group in Division of Basic Sciences, received a new 2-year $431,750 Exploratory/Developmental Research Grant Award (R21) from the National Institute of Neurological Disorders and Stroke (NINDS) for his research project entitled “Resolution of chemotherapy-induced peripheral neuropathy by novel lipid mediator”. This is Dr. Xu’s first NIH Award. Chemotherapy-induced peripheral neuropathy (CIPN) is the dose-limiting toxicity for many commonly used classes of anti-cancer agents. CIPN can lead to dose reductions or discontinuation of cancer therapy. In particular, taxanes, such as paclitaxel, remain the most effective and usually used drugs in human chemotherapy; unfortunately, they cause painful neuropathy in most cancer patients receiving chemotherapy. Currently, there are no FDA-approved interventions or prevention strategies for CIPN. CIPN results in morphological and functional insults to the peripheral nervous system, including dorsal root ganglion (DRG) abnormalities, oxidative stress, activation of glial cells, release of pro-inflammatory cytokines, and loss of epidermal innervations. Disruption of acute resolution processing may lead to uncontrolled inflammation and chronic pain. Neuroprotectin D1 (NPD1) is a newly identified endogenous lipid mediator biosynthesized from omega-3 fatty acids, and demonstrates potent anti-inflammatory and pro-resolving actions. The central hypothesis of this project is that NPD1 may prevent and reverse chemotherapy-induced neuropathic pain, by resolving CIPN-induced neuroinflammation, glial activation, neuronal hyperactivity, and loss of epidermal innervations. These studies will focus on chemotherapy-induced neuropathic pain, as well as determine the mechanisms by which the endogenous lipid mediator to resolve CIPN. We hope the planed project will demonstrate novel molecular and cellular mechanisms of CIPN and help develop new therapy for treating chronic pain associated with CIPN.
Jeffrey Taekman MD, Assistant Dean for Educational Technology, Director of the Human Simulation and Patient Safety Center and Faculty, Duke Center for Health Informatics-in collaboration with Applied Research Associates (ARA), was awarded a 12-month contract from the U.S. Army Research, Development, and Engineering Command (RDECOM) (of which $122,052 will be coming to Duke University), for a project entitled “Virtual Patient Technology with Virtual Worlds Technology (HumanSim: Combat Medic)”.
HumanSim: Combat Medic is an exciting educational program designed to train Army medics and other military medical personnel in medical and teamwork skills within an immersive, virtual environment. Developed as a scalable and widely deployable supplement to existing training materials, this engaging “serious game” seeks to address and prevent the top causes of death in the modern battlefield. HumanSim: Combat Medic delivers content through self-directed, team-based, and instructor-led medical training activities accessible from any internet-connected computer. This innovative platform also features virtual meeting spaces for pre- and post-game discussions, a robust debriefing platform, and a modular design for future expansion. Key personnel include Dr. John Lemm and Mr. Al Bonifacio.
Michael Manning, MD, PhD, Research Fellow and Medical Instructor in the Division of Cardiothoracic Anesthesiology was awarded a two-year $50,000 Society of Cardiovascular Anesthesiologists (SCA) Starter Grant entitled “Atrial Fibrillation Following Cardiopulmonary Bypass: The Role of Angiotensin II”.
Post-operative atrial fibrillation (POAF) occurs in 30-60% of cardiac surgical patients, and is associated with increased morbidity and mortality. Preventative treatment options for this significant problem are lacking, with most therapy instituted after onset of POAF when associated risks, including stroke, are highest. Evidence suggests a key role for inflammation in the genesis and perpetuation of POAF through structural changes in the atrial wall; this may serve as a point for intervention and prevention, thereby decreasing overall morbidity and mortality.
Patients who undergo cardiac surgery with cardiopulmonary bypass (CPB) experience a significant inflammatory reaction, which has been thought to be responsible for some degree of organ injury during the postoperative period. Concurrent with the CPB-induced inflammatory responses there is a significant increase seen in the circulating levels of Angiotensin II. This increase coincides with the appearance of POAF, usually by posteroperative day 2 or 3.
We believe that Angiotensin, which has been previously shown to be intimately involved in inflammation in the cardiovascular system, may be playing a role in the development of POAF following cardiac surgery. Angiotensin II could potentially be signaling inflammatory cells such as macrophages and monocytes to the heart, as part of this overall inflammatory state. This influx of inflammatory cells may be acutely altering the extracellular matrix within the heart wall to change electrical conduction, and thereby promote the development of POAF.
Using a well-established rat model of CPB, we will test the hypothesis that: CPB increases myocardial AngII expression, which modulates an inflammatory response, leading to cellular infiltration of the atrial wall and cardiac structural remodeling. We believe that the influence of AngII on myocardial inflammation leading to POAF represents a current gap in understanding of the pathogenesis of AF. Furthermore, believe that AngII may play a significant, and as yet unrecognized role in modulating this pathology.
Melissa Christiansen, PhD, Research Associate in the Molecular Genetics of Pain Signaling Laboratory of the Division of Basic Sciences, received a 1-year $49,843 Postdoctoral Fellowship Award from the Ruth K. Broad Biomedical Research Foundation for her project entitled “A high-throughput ballistic screen for genes mediating mechanical nociception in Drosophila.” The major goal of her Postdoctoral Fellowship is to identify new genes that are specifically involved in the sense of mechanical pain.
W. Dan Tracey, PhD, of the Division of Basic Sciences and Director of the Molecular Genetics of Pain Signaling Laboratory (along with Ming Guo, MD, PhD at the University of California Los Angeles) have been selected to receive a two year $300,000 Collaborative Research Grant from the Ruth K. Broad Biomedical Research Foundation for their project entitled “X11, Dendrites, and Alzheimer’s Disease”. The major goals of this project are to understand the role of the X11 gene in dendrite morphogenesis and function. In addition, the relationship of X11 with molecular pathways implicated in Alzheimer’s disease will be investigated.
Congratulations to one of our 2013 DREAM Innovation Grant recipients, Karthik Raghunathan, MD, who was recently awarded the $100,000 APSF/ASA Endowed Research Award from the APSF Scientific Evaluation Committee for his research study, “Comparative safety of different types of IV fluids for resuscitation in the OR and ICU: an applied pharmacoepidemiologic approach.”
This is the second extramural funding grant that Dr. Raghunathan has received this year for his DIG research project. In the Summer of 2013, Dr. Raghunathan was awarded a $206,944 grant from the Baxter Healthcare Corporation fluids franchise. This makes his total extramural funding at $306,944 to date.