Neural Discovery at Duke is the Newest Cover of Nature

New research from two Duke University labs in the departments of anesthesiology and cell biology finds that astrocytes and their unique architecture play a significant role in regulating the development and function of synapses in the brain. The manuscript, titled “Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis,” was published in the November 9, 2017 issue of Nature and featured as the journal’s cover story. Duke Anesthesiology authors include Dr. Ru-Rong Ji, chief of pain research, Dr. Yong-Ho Kim and Di Liu.

An astrocyte (blue) grown in a dish with neurons forms an intricate, star-shaped structure. Neurons’ synaptic proteins appear in green and purple. Overlapping proteins represent the locations of synapses. Credit: Jeff Stogsdill, Duke University

An astrocyte (blue) grown in a dish with neurons forms an intricate, star-shaped structure. Neurons’ synaptic proteins appear in green and purple. Overlapping proteins represent the locations of synapses. Credit: Jeff Stogsdill, Duke University

According to the article, titled “Star-Shaped Brain Cells Orchestrate Neural Connections,” published by Duke TODAY and featured on Duke University’s Med School Blog, this study highlights that the dysfunction of intricate astrocyte cells may underlie devastating diseases such as autism, schizophrenia and epilepsy. The article goes on to state that the Duke team identified a family of three proteins that control the web-like structure of each astrocyte as it grows and encases neuronal structures such as synapses. Switching off one of these proteins not only limited the complexity of the astrocytes, but also altered the nature of the synapses between neurons they touched, shifting the delicate balance between excitatory and inhibitory neural connections.

Dr. Cagla Eroglu, co-author and associate professor of cell biology and neurology at Duke adds that, “We found that astrocytes’ shape and their interactions with synapses are fundamentally important for brain function and can be linked to diseases in a way that people have neglected until now.”

A 3-D-printed model of a single astrocyte from a mouse brain shows the sponge-like structure of these cells. Photo credit: Katherine King, Duke University.

A 3-D-printed model of a single astrocyte from a mouse brain shows the sponge-like structure of these cells. Photo credit: Katherine King, Duke University.

Ben Barres, a professor of neurobiology at Stanford University, who was not involved with the study, praised the findings as “a profoundly important, revolutionary advance” for understanding how interactions between neurons and astrocytes can affect synapse formation.

Dr. Ji is a distinguished professor of anesthesiology in the Duke University School of Medicine, co-director of Duke Anesthesiology’s Center for Translational Pain Medicine and a member of the Duke Institute for Brain Sciences. His Sensory Plasticity and Pain Research Laboratory focuses on identifying molecular and cellular mechanisms that underlie the genesis of chronic pain and developing novel pain therapies that can target those mechanisms.

Chris KeithNeural Discovery at Duke is the Newest Cover of Nature
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Dr. Terrando Receives Prestigious R01 Award

Niccolo Terrando, PhDThe National Institutes of Health/National Institute on Aging (NIH/NIA) has awarded Duke Anesthesiology’s Niccolò Terrando, BSc, DIC, PhD, a five-year, $2,815,756 R01 Award for his project, titled “Neurovascular dysfunction in delirium superimposed on dementia.”

Millions of Americans live with dementia and require common surgical interventions, such as orthopaedic surgery. According to the research statement, these potentially life-saving procedures often increase the risk for further cognitive deterioration and in many cases, even death. Dr. Terrando with his team of investigators at Duke University (Carol Colton, Gurpreet Baht, William Wetsel, Zhiquan Zhang, and Miles Berger) and University of Rochester Medical Center (Harris Gelbard) will address this public health concern by providing fundamental knowledge expected to help reduce the burdens of neurologic complications after common surgical procedures, and improve the quality of life for these high-risk patients.

The rationale for the proposed research is that successful completion of these studies will advance and expand the understanding of how surgery affects the blood-brain interface, and will provide new insights into molecular mechanisms of relevance to delirium, neurodegeneration and aging. Such knowledge is highly significant because it has the potential to improve surgical outcomes and quality of life for millions of vulnerable, elderly patients in the United States by using new therapeutic approaches tested in this grant.

As stated in the project’s abstract, impaired cognitive function after common surgical procedures is a growing concern, especially among the more than five million people in the nation who suffer from dementia, including Alzheimer’s disease (AD), and thus have a three-fold increased risk for fracture requiring surgical repair. After orthopaedic surgery, acute changes in cognitive function, often referred to as postoperative delirium, occur in up to 89 percent of patients with preexisting dementia, and associate with poorer prognosis and even two-fold greater risk for one-year mortality compared to patients without dementia or delirium. This proposal will attempt to model postoperative delirium superimposed on dementia after orthopaedic surgery using innovative approaches to understand, and possibly attenuate, the effects of surgery on the blood–brain interface, including the neurovascular unit (NVU) and the blood-brain barrier (BBB).

The long-term goal of Dr. Terrando and his team of investigators is to define the mechanisms that underlie surgery-induced cognitive dysfunction, and to provide safe and effective approaches to reduce this potentially devastating complication.

Dr. Terrando joined Duke in 2015 and is an assistant professor in anesthesiology, the director of the Neuroinflammation and Cognitive Outcomes Laboratory, a collaborator of Duke Anesthesiology’s Center for Translational Pain Medicine and a 2016 DREAM Innovation Grant (DIG) recipient for his research project, titled “The Systemic Milieu and its Role in Postoperative Cognitive Dysfunction.”

Chris KeithDr. Terrando Receives Prestigious R01 Award
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Dr. Zhang Wins Poster Award at Inaugural Pain Meeting

Dr. Zhang with is award winning poster.

Dr. Zhang with is award winning poster.

Duke Anesthesiology’s Xin Zhang, MD, PhD, received an award for “Outstanding Poster” at the first Translational Pain Research Symposium, held on June 21 – 23 at Duke Kunshan University in China. His poster is titled, “Activation of peripheral β2 and β3ARs leads to increased nociceptor activity.”

Zhang and Nackley China June 2017

Zhang and Nackley China June 2017

As noted in the abstract, Dr. Zhang’s research shows that i) COMT inhibition leads to pain sensitivity, in line with increased ERK phosphorylation in DRG neurons and strengthened nociceptor activity in response to noxious stimuli, ii) COMT-dependent increases in pain sensitivity and nociceptor activity are driven by peripheral β2- and β3ARs, and iii) treatments targeted towards peripheral β2- and β3ARs and downstream effectors may prove useful in the management of functional pain syndromes. The team of investigators includes Duke Anesthesiology’s Andrea Nackley, PhD, Seungtae Kim, MD, PhD, and Sandra O’Buckley.

Dr. Zhang is a postdoctoral fellow with The Nackley Lab, part of Duke Anesthesiology’s Center for Translational Pain Medicine which is dedicated to unraveling the causes of painful conditions to better improve patient care. The Translational Pain Research Symposium was held on the new state-of-the-art campus of Duke Kunshan University. The goals of the conference were to present recent advances in basic science research of pain mechanisms, introduce cutting-edge techniques in pain research, and bridge the gap between basic research and clinical applications.

Chris KeithDr. Zhang Wins Poster Award at Inaugural Pain Meeting
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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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