Pain Researcher Awarded NIH Grant

Andrea Nackley, PhDThe National Institutes of Health’s National Institute of Dental and Craniofacial Research has awarded Andrea Nackley, PhD, a $500,000, one-year grant for her project titled, “Proteins, MicroRNAs and Genes Associated with TMD and Overlapping Conditions.”

According to the Institute of Medicine, chronic pain affects 100 million Americans, causing extensive economic, social and personal costs. For some, the pain remains localized, while for others the pain spreads to affect multiple anatomic sites, suggesting a common underlying cause. In response to PA-14-244, Dr. Nackley plans to use stored biospecimens and existing data from a clinical study of 1,460 adults to determine biological (proteins, microRNAs, and gene polymorphisms), psychosocial (stress, depression, anxiety), and clinical (general health and environmental exposures) factors that contribute to localized and overlapping pain conditions. They will also use bioinformatics methods to understand how these factors interact to influence pain with the long-term goal to identify biomarkers for the diagnosis and treatment of chronic overlapping pain conditions.

Dr. Nackley is the director of The Nackley Lab, part of Duke Anesthesiology’s Center for Translational Pain Medicine. This center began in January of 2016 and represents a novel entity established to transform the way painful conditions are diagnosed and treated. This new center  further expands Duke Anesthesiology’s existing clinical and research program in innovative pain therapies by bringing together, under one umbrella, leading basic scientists, clinicians and clinical researchers who have a common core mission of unraveling the causes of painful conditions to better improve patient care.

Chris KeithPain Researcher Awarded NIH Grant
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DREAM Campaign Support Results in NIH Grant

Jordt Lab Group

The National Institutes of Health has awarded Dr. Sven-Eric Jordt’s Duke Anesthesiology laboratory a two-year, $384,780 grant from its National Institute of Arthritis and Musculoskeletal and Skin Diseases for their project titled, “Mechanisms of Itch in Poison Ivy-Induced Allergic Contact Dermatitis.”

This R21 grant will support highly innovative research to identify mechanisms of itch. “Conditions such as allergic contact dermatitis, atopic dermatitis and psoriasis are widespread, with patients suffering from strong untreatable itch,” says Dr. Jordt, who adds that the sensation of itch is related to the sensation of pain which is triggered by related nerve pathways. “However, itch research has clearly lagged behind pain research and there is a great need for new treatments.”

This success was made possible with support from a DREAM Innovation Grant (DIG) to Dr. Boyi Liu in Dr. Jordt’s Chemical Sensing, Pain and Inflammation Research Laboratory. This lab focuses on the mechanisms that enable humans and animals to sense touch, pain and irritation.

The DIG is part of Duke Anesthesiology’s DREAM (Developing Research Excellence in Anesthesia Management) Campaign, endowed by philanthropic gifts to the department, which supports innovative high-risk and potentially high-reward investigations to accelerate anesthesia and pain management to improve patient care. Dr. Liu recently joined the faculty of Zhejiang Chinese Medical University in Hangzhou, China, and will continue collaborating with Dr. Jordt’s group.

Chris KeithDREAM Campaign Support Results in NIH Grant
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Four Departments, One $3M Grant

Dr. Joseph Mathew & Dr. Charles HughesThe National Institutes of Health and the National Heart, Lung, and Blood Institute have awarded the chairman of Duke Anesthesiology, Dr. Joseph Mathew, and the co-principal investigator, Dr. Charles Hughes, a $3.5 million, five-year R01 award for their project titled, “Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest.”

This research endeavor in the Department of Anesthesiology will bring together the departments of Psychiatry, Cardiac Surgery, Biostatistics and Bioinformatics, as well as external academic institutions such as the University of Pennsylvania and Emory University. Co-investigators include Drs. Jeffrey Browndyke, Joern Karhausen, Yi-Ju Li, Mark Newman, and Wulf Paschen.

The use of deep hypothermia (<20°C) for cerebral protection ushered in the modern era of safe and effective operations on the heart and aorta. In large part due to advanced circulatory management strategies, surgical procedures on the proximal aorta and arch utilizing deep hypothermic circulatory arrest have steadily increased over the last decade. Despite these advances, neurologic complications remain a sobering limitation. Indeed, 7-13 percent of patients endure permanent neurologic dysfunction. In addition, postoperative cognitive decline (POCD) occurs in 36 percent of cardiac surgery patients at six weeks after surgery, and importantly, persists in 42 percent of patients up to five years after surgery and reduces quality of life. Although deep hypothermia has been the standard of care for decades in adult patients requiring circulatory arrest, moderate hypothermia is now more commonly used in many centers. However, this transition to moderate temperatures has been based entirely on observational studies that have not adequately assessed neurological or neurocognitive outcomes.

In the proposed study, the team will test their hypothesis that deep hypothermia (<20°C) during surgical circulatory arrest limits POCD and preserves brain connectivity to a greater degree than moderate hypothermia (24.1°C-28°C) and that low hypothermia (20.1°C-24°C) is non-inferior to deep hypothermia. This proposed study will be the first randomized trial to evaluate the effects of deep vs. low vs. moderate hypothermia during circulatory arrest on neurocognitive function and functional brain connectivity. Preliminary data strongly supports a detrimental effect of moderate hypothermia during circulatory arrest and this study is likely to dramatically alter practice and improve patient safety. This study will also be the first study in humans to assess the role of the small ubiquitin-like modifier conjugation pathway in protecting the brain during cardiac surgery requiring circulatory arrest. This significant study is expected to vertically advance the field of cardiac surgery by revolutionizing our understanding of the effects of hypothermia on neurologic and neurocognitive outcomes, by providing strong evidence for optimal hypothermic temperatures during surgical circulatory arrest, and by identifying new targets for therapeutic intervention to increase the resistance of organs to a transient interruption in blood supply.

Little is more devastating to a patient or the patient’s family than to have a successful operation that prolongs life, but is complicated by cognitive impairment resulting in a diminished quality of life and loss of functional independence. The long-term goal of the multidisciplinary Neurologic Outcome Research Group is to understand the mechanisms underlying neurologic and neurocognitive dysfunction after cardiac surgery, and to reduce the incidence of these devastating outcomes.

Chris KeithFour Departments, One $3M Grant
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Duke Team Receives Research Incubator Award

Niccolò Terrando, BSc (hons), DIC, PhDThe Duke Institute for Brain Sciences (DIBS) has awarded a 2016 DIG receipient, Niccolo Terrando, PhD, and his team of five co-investigators, a $75,000 grant for their project titled, “Bioelectronic Medicine and Cholinergic Regulation of Postoperative Cognitive Dysfunction.”

Millions of individuals in the U.S. undergo surgery every year for medically necessary conditions and are at risk for developing memory impairments, including postoperative delirium and long-lasting postoperative cognitive dysfunction (POCD). Although risk factors, including age, have been identified, the mechanisms underlying surgical effects on cognitive outcomes are unknown. Thus, there is an urgent need to characterize the mechanisms  that lead to memory dysfunction after surgery and to develop safe and effective therapeutic strategies against this potentially devastating complication. The DIBS 2016-2017 Research Incubator Award will explore the potential for bioelectronic medicine as a novel intervention to prevent POCD. Using a clinically-relevant model of orthopedic surgery in mice, the Duke team linked surgical procedures to the development of inflammation in brain regions that are responsible for overall memory function. Previous work revealed that pharmacological activation of a cholinergic anti-inflammatory reflex can mitigate neuroinflammation and POCD in mice.

The project brings together a multidisciplinary group of investigators with diverse, unique, and complementary expertise from three schools within Duke University (School of Medicine, Pratt School of Engineering, and Arts & Sciences), representing four departments (Anesthesiology, Cell Biology, Biomedical Engineering, Psychology and Neuroscience ). Co-investigators include Professor Warren Grill, Professor Christina Williams, Associate Professor Chay Kuo, Assistant Professor Miles Berger and Associate Professor Staci Bilbo. This is set to provide both basic and translational knowledge in the field of perioperative care: from a basic science perspective, it will explore the fundamental relationship between inflammation, cholinergic function, and memory using a clinically relevant model of peripheral surgical trauma; from a translational perspective, this work will provide a novel therapeutic approach to treat POCD without directly disrupting the innate immune responses to trauma.

Chris KeithDuke Team Receives Research Incubator Award
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Grant Awarded to Study High-Risk Transplants

Drs. Mihai Podgoreanu and Quintin QuinonesThe Duke University School of Medicine has awarded Drs. Mihai Podgoreanu and Quintin Quinones a $10,000 grant for their project titled, “Sequencing Technology for Rapid Detection of Fastidious and Resistant Infectious Agents in the Critically Ill.”

Infectious disease is a major contributor to mortality in critically ill patients, particularly those who are immunosuppressed. The immediate post-transplant population is acutely at risk for infection given the heavy doses of induction immunosuppression needed to prevent allograft rejection. Of all solid organ transplants, lung transplant patients are particularly at risk for infection, as the recipient is frequently colonized with resistant pathogens pre-transplant; after transplant, the graft is continuously exposed to pathogens from the environment.

Drs. Podgoreanu and Quinones’ central hypothesis is that they can rapidly detect and identify infectious microorganisms, and in some cases, determine their antibiotic resistance patterns using nucleic acid amplification and sequencing technology. With this information, they believe they can more rapidly tailor care plans and antimicrobial therapy for our critically ill lung-transplant recipients. The successful completion of this project will establish a potential rapid assay for the detection of fastidious and often multi-drug resistant organism that is highly relevant to the care of post-lung transplant patients in the cardiothoracic intensive care unit. Additional transformational results of using such sequencing diagnostics directly from respiratory specimens include differentiating colonizers versus pathogens, viral from bacterial pathogens, and phenotypic resistance.

Duke University Medical Center is a high-volume transplant center, particularly for heart and lung transplants. A collaboration is now being formed between physician-scientists in the cardiothoracic intensive care unit, infectious disease, and genomic and computational biologists at Duke University. The awarded funds will cover a portion of the cost of sequencing the genomes of the reference panel and developing a genotyping test panel. These services will be provided by the Genome Sequencing and Analysis Shared Resource.

Chris KeithGrant Awarded to Study High-Risk Transplants
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