Neuroscientists Awarded School of Medicine Voucher

The Duke University School of Medicine has awarded an $8,000 voucher to Duke Anesthesiology’s Niccolò Terrando, PhD, and Zhiquan Zhang, PhD, for their project, titled “Preventing Memory Dysfunction after Surgery with a Novel Pro-Resolving Peptide from Annexin-A1.”

Major surgery, including cardiac and orthopedic, often causes neurological complications such as delirium and postoperative cognitive dysfunction. According to the project investigators, there are currently no safe and effective therapies to prevent or limit these complications in patients. Dr. Zhang previously developed a bioactive peptide (ANXA1sp) derived from the N-terminal domain of the human protein Annexin-A1 (ANXA1), a critical molecule involved in the resolution of inflammation. Ongoing studies with this peptide are revealing promising effects in protecting the brain against excessive neuroinflammation after surgery, which is becoming a key contributor to memory deficit.

This voucher, in collaboration with the Mouse Behavioral and Neuroendocrine Shared Core, will help Drs. Zhang and Terrando validate the effects of this peptide on cognitive, as well as higher order memory tasks, in their models of cognitive dysfunction after major surgery. Given the impact of neuroinflammation on memory function across many different neurological disorders, this therapy could provide fundamental knowledge to direct future studies and therapy development for numerous conditions such as Alzheimer’s disease and other dementias.

Dr. Terrando is an assistant professor in anesthesiology, a collaborator with Duke Anesthesiology’s Center for Translational Pain Medicine and the director of the Neuroinflammation and Cognitive Outcomes Laboratory which studies the mechanisms underlying postoperative neurocognitive disorders with a strong focus on neuroinflammation, innate immunity and behavior. Dr. Zhang is an assistant professor in anesthesiology and a member of Dr. Terrando’s lab.

Chris KeithNeuroscientists Awarded School of Medicine Voucher
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Dr. Maixner Appointed Vice Chair for Research

William Maixner, DDS, PhDWe are pleased to announce that William Maixner, DDS, PhD, has been appointed as the Vice Chair for Research at Duke Anesthesiology, effective July 1, 2017.

“It’s a great honor to assist the department and the university in promoting research and scholarship and to expand our presence on the national and international stage,” says Dr. Maixner. “I have been offered a unique opportunity to move our department forward and create a unique space for anesthesia research in the domain of translational medicine.”

Dr. Maixner’s appointment comes on the heels of David S. Warner, MD, a Distinguished Professor of Anesthesiology, retiring from the position of Vice Chair for Research which he has held since 2001, positively impacting the careers and research directions of Duke Anesthesiology trainees and faculty for the past 16 years. “The department has made a remarkable team effort to grow our academic mission and position itself for a brilliant future in advancing patient care. It’s been a tremendous honor and a joy to be a part of it,” says Dr. Warner. “I want to express gratitude to the entire department for their contributions, all of which have been essential.”

Dr. Maixner was recently named the Joannes H. Karis, MD, Professor of Anesthesiology, and is the director of Duke Anesthesiology’s Center for Translational Pain Medicine and Duke Innovative Pain Therapies (a first-of-its-kind, multispecialty pain practice at Brier Creek). In his new role as Vice Chair for Research, Dr. Maixner will develop an interdisciplinary strategy for the department and continue to lead efforts to grow, promote, and support research and scholarship of programs in pain medicine/mechanisms, cognitive decline after surgery, transfusion medicine, organ preservation and resuscitation, perioperative genomics, obstetrics, simulation and safety, and hyperbaric medicine. He will also develop a multidisciplinary research vision, strategically leading and identifying novel investigative opportunities, while ensuring that junior faculty members establish formal career development plans with aggressive, but realistic, timelines and milestones in a pathway to research independence.

“Dr. Warner has made a significant mark within this department, university and the national level; I have some big shoes to fill. He has set a standard for me to look towards and to strive to achieve,” says Dr. Maixner. “I look forward to working with Dr. Warner during this transition, and it’s my hope and goal that we’ll be working arm-in-arm as we move forward on developing initiatives and research activities. He’s passing the baton, but we’re part of the same relay.”

“We are now in a position to harness the many resources that have been created to develop a mature and programmatic strategy that will provide focused collaborations, training, and innovation, yet still support a critically important inclusive culture,” adds Dr. Warner. “There is no better person than Dr. Maixner to take our mission to the next level. He has already proven his capability to achieve this vision.”

Please join us in extending congratulations to Dr. Maixner and thanking Dr. Warner for his many years of outstanding service to all of us.

Chris KeithDr. Maixner Appointed Vice Chair for Research
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Dr. Jordt Named Co-Chair of Terrorism & Inhalation Disasters Section

Sven-Eric Jordt, PhDThe American Thoracic Society (ATS) elected Duke Anesthesiology’s Sven-Eric Jordt, PhD, as the co-chair of its Section on Terrorism and Inhalation Disasters (TID) on May 23 at the society’s annual meeting.

TID brings together ATS members with interests in mechanisms and treatment approaches for chemically-induced inhalation injuries and their health effects, epidemiology of inhalation injuries, identification and control of inhalation threats associated with terrorism, industrial accidents, infectious diseases and environmental disasters, preparedness and first responder networks. Dr. Jordt will support the section’s mission by coordinating section proposals, official society publications and outreach efforts.

An ATS report calling for an increase in research efforts to develop new therapeutics for chemical inhalation injury was published in the June 1, 2017 issue of the Annals of the American Thoracic Society, titled “An Official American Thoracic Society Workshop Report: Chemical Inhalational Disasters. Biology of Lung Injury, Development of Novel Therapeutics, and Medical Preparedness.”

Dr. Jordt is an associate professor of anesthesiology, faculty of Duke Anesthesiology’s Center for Translational Pain Medicine, and the director of the Chemical Sensing, Pain and Inflammation Research Laboratory which focuses on the mechanisms that enable humans and animals to sense touch, pain and irritation.

Chris KeithDr. Jordt Named Co-Chair of Terrorism & Inhalation Disasters Section
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Promising Neuroprotection Strategy Published in Stroke

Translational stroke research is in a critical phase, according to Duke Anesthesiology’s Wulf Paschen, PhD, and Wei Yang, PhD, whose research was published in the June 2017 issue of the journal, Stroke, titled “XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.” Their study reveals a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome, noting that boosting prosurvival pathways to counterbalance the age-related decline in the brain’s self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.

Drs. Wulf Paschen and Wei YangAs the co-authors of this manuscript report, positive outcomes from neuroprotection treatment strategies aimed to minimize stroke damage have been reported in many pre-clinical stroke studies, but could not be repeated in clinical stroke trials. Many factors that potentially contribute to this disparity in outcomes have been identified. Age has attracted little attention as a factor potentially contributing to unsuccessful translational stroke research, even though the neuroprotection strategies that failed in clinical trials on elderly stroke patients were developed in experimental stroke studies performed primarily in young animals.

Drs. Paschen and Yang’s Molecular Neurobiology Laboratory is working on understanding the mechanisms contributing to the effect of age on stroke outcome. The pathophysiology of acute ischemic stroke has been investigated extensively in animal models. Traditional neuroprotection strategies were designed to improve stroke outcome by interfering with pathological processes triggered by ischemia. However, stroke outcome is also dependent on the brain’s capacity to restore cellular functions impaired by ischemia, and this capacity declines with age. In acute ischemic stroke, irreversibly damaged tissue – the ischemic core – is surrounded by metabolically compromised but still viable and salvageable tissue – the penumbra. The penumbra is, therefore, the primary target for stroke therapy to block the expansion of the ischemic core into the penumbra.

We know that maintenance of protein homeostasis (proteostasis) is key to keep cells functional. We also know that proteostasis is impaired with increasing age,” says Dr. Paschen. “Our current focus of research is to understand the effect of age on maintenance of proteostasis in the stroke penumbra. We found that a cellular pathway playing a pivotal role in restoration of proteostasis impaired by stress is activated in neurons located in the stroke penumbra in young mice but impaired in aged mice (see Stroke manuscript).” Dr. Paschen adds that notably, the dysfunctional proteostasis in the stroke penumbra is associated with worse stroke outcome and can be rescued pharmacologically to improve stroke outcome. He says their pharmacologic strategy can also help neurons to better withstand ischemic stress conditions when provided several hours before the ischemic challenge. This team of investigators expects their observations to have a major impact on translational stroke research and also be of interest for perioperative organ protection.

Dr. Paschen is a professor in anesthesiology in the Basic Science Division and a research professor in neurobiology. Dr. Yang is an assistant professor in anesthesiology, also in the Basic Science Division within Duke Anesthesiology.

Chris KeithPromising Neuroprotection Strategy Published in Stroke
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