Dr. Terrando Awarded Grant to Study Delirium Therapy

Niccolò Terrando, BSc (hons), DIC, PhDExalys Therapeutics has awarded Duke Anesthesiology’s Niccolò Terrando, PhD, a $200,479 grant for his project, “Test the Efficacy of Exalys EP4 Antagonist to Prevent Neuroinflammation and Delirium in a Preclinical Model.” The project will study the efficacy and safety of Exalys’ lead Prostaglandin E2 receptor 4 (EP4) antagonist in preventing cognitive decline (inattentiveness) and associated inflammatory biomarkers in a surgical preclinical model of delirium (orthopedic fracture). Results from this study could advance the development of a new immune-drug target to combat delirium. Terrando and Dr. Ting Yang of Duke Medicine serve as co-principal investigators.

Postoperative delirium, also referred to as “acute brain failure,” is a common and serious surgical complication in older patients that can lead to increased hospital costs and poor post-discharge outcomes. The ongoing pandemic due to COVID-19 has further highlighted the multiple challenges related to treating patients with delirium, especially given the limited therapeutic options available. Despite the prevalence of delirium in multiple settings, ranging from critical illness to elective surgical procedures, there are currently no therapies to possibly prevent delirium.

Delirium is a challenging, multifactorial pathology, with several mechanisms impacting the brain functioning of vulnerable patients. The Neuroinflammation and Cognitive Outcomes Laboratory, directed by Terrando at Duke Anesthesiology, has identified a critical role of systemic inflammation in driving “acute brain failure” and causing pathologic and behavioral changes in rodent models that resemble features of human delirium.

“Inflammation truly is a double edge sword in the setting of perioperative recovery,” says Terrando, associate professor in anesthesiology. “We know many of the deleterious effects that pro-inflammatory molecules can exert on the brain. We also know that blocking these molecules can impair the recovery of postoperative patients, for example by impairing healing.” Yang and Terrando recently contributed a review in Nature Immunology discussing the role of innate immunity in driving perioperative neurocognitive disorders, such as delirium.

“We are thrilled for the opportunity provided by Exalys to test and expand the potential application of this new compound to prevent delirium,” Yang adds. Her laboratory is actively studying the role of EP4 signaling in cardiovascular disorders, including hypertension and brain inflammation.

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Dr. Ji Named a Highly Cited Researcher

Ru-Rong Ji, PhDDuke Anesthesiology’s Ru-Rong Ji, PhD, distinguished professor of anesthesiology, has once again been named among the most “Highly Cited Researchers” in the world. Ji is one of 37 Duke faculty named to the list this year; he is one of 22 faculty from the Duke University School of Medicine.

The annual list is based on the number of highly cited papers produced over an 11-year period from January 2009 to December 2019. Citation rate, as tracked by Clarivate’s Web of Science, is an approximate measure of a study’s influence and importance. 6,127 researchers from 60 countries are recognized by the 2020 listing.

Ji was one of 54 Duke researchers who made the global list of “Highly Cited Researchers” in 2019; a list he also made in 2018. His research focuses on molecular and cellular mechanisms of chronic pain, including but not limited to mediators of inflammation and pain, neuropathic pain and cancer pain.

“This list is very dynamic from year to year,” says Ji, director of the Sensory Plasticity and Pain Research Laboratory and co-director of the Center for Translational Pain Medicine at Duke Anesthesiology. “I am very pleased that someone from anesthesiology can make the list. I am proud to represent the field, and I appreciate the strong support for my research from the department.”

The year’s most highly cited authors from the Duke University School of Medicine are: 

Robert M. Califf—Clinical Medicine
Avshalom Caspi—Psychiatry and Psychology
Jane Costello— Psychiatry and Psychology
Lesley H. Curtis—Clinical Medicine
Geraldine Dawson— Cross-Field
Pamela S. Douglas—Clinical Medicine
Charles A. Gersbach—Cross-Field
Christopher Bull Granger—Clinical Medicine
Barton F. Haynes—Immunology and Microbiology
Adrian F. Hernandez—Clinical Medicine
Ru-Rong Ji—Cross-Field
Robert J. Lefkowitz—Clinical Medicine
Sarah H. Lisanby—Cross-Field
Jason Locasale— Cross-Field
Edward A. Miao—Immunology
Terrie E. Moffitt—Psychiatry and Psychology
Kristen Newby—Clinical Medicine
Christopher B. Newgard—Cross-Field
Erik Magnus Ohman—Clinical Medicine
Manesh R. Patel—Clinical Medicine
Michael J. Pencina—Social Sciences and Clinical Medicine
Eric D. Peterson—Clinical Medicine

For a complete list of Duke faculty, see the article at Duke Research Blog.

Source: Duke Med School Blog, November 19, 2020

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Dr. Martucci Earns Research Incubator Award

Katherine Martucci, PhDDuke Anesthesiology’s Katherine Martucci, PhD, is among the investigators on a cross-departmental research team that has been awarded a 2020 Research Incubator Award ($75,000 grant) from the Duke Institute for Brain Sciences (DIBS) for their project titled, “Neural Mechanisms Underlying Tobacco Withdrawal-Induced Hyperalgesia.”

This award is designed to promote high-risk/high-return neuroscience research that is collaborative, crosses disciplinary boundaries, and is likely to draw external funding. The collaborative project brings together Martucci, and Duke Psychiatry & Behavioral Sciences’ Drs. Maggie Sweitzer, F. Joseph McClernon and Alison Adcock.

Chronic pain and cigarette smoking influence one another, in that smokers are more likely to have pain, and individuals with pain are more likely to smoke. People with chronic pain have more difficulty quitting smoking, in part, because temporarily going without smoking (early withdrawal) leads to increased pain sensitivity.

The goal of the study is to examine the brain’s response to heat pain stimuli among smokers in early withdrawal, to better understand the reasons for increased pain sensitivity. Daily smokers will complete two fMRI sessions, one after smoking as usual, and one after not smoking for 24 hours. During the scans, participants will experience heat pain delivered through an electrode and will provide ratings of their pain response. It is expected that participants’ ratings of pain in response to heat stimuli will be greater during the withdrawal session, and that this increased pain will be associated with greater activation throughout a network of brain regions involved in perceiving pain. This approach will allow the research team to determine which brain regions are most involved in pain sensitivity during withdrawal and which will help to identify targets for treatment. In addition, these processes might differ among smokers who also have chronic pain, compared to those who do not. As such, half of the participants will be those diagnosed with chronic pain, while the other half will be pain-free. The investigators anticipate that the effects of smoking withdrawal on pain-related brain function will be more pronounced among those with chronic pain.

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In Remembrance of Dr. William Maixner

William Maixner, DDS, PhDIt is with profound sadness that we inform you about the passing of a beloved member of our Duke Anesthesiology family, William “Bill” Maixner, DDS, PhD. He passed away on November 2 at the age of 68 after battling an illness. Duke flags were lowered on November 4 in honor of his life and legacy.

Dr. Maixner, the Joannes H. Karis, MD, Professor of Anesthesiology, was a world-renowned pioneer in pain research and one of our department’s most distinguished faculty. He will be remembered as an extraordinary leader, innovator, scientist and mentor who dedicated his life-long career to unraveling the mysteries of chronic pain and was committed to translating basic discoveries into novel diagnostics and treatments to positively impact research, education and patient care.

On January 1, 2016, Dr. Maixner joined our department from the School of Dentistry at the University of North Carolina at Chapel Hill (UNC-CH), where he was the Mary Lily Kenan Flagler Bingham Distinguished University Professor, to further expand our clinical and research program in pain medicine. During his short time with us here at Duke, he achieved incredible milestones. Dr. Maixner developed and led the Center for Translational Pain Medicine, which recently received the rare and prestigious designation as a National Center of Excellence through an $8.5 million National Institutes of Health (NIH) program project grant (PPG), the first PPG in 40 years awarded to our department. He was a visionary who brought to fruition a center that united leading basic scientists, clinicians and clinical researchers under one umbrella, with the core mission of developing novel pain therapies to improve patient care. Through his leadership, this center has rapidly become internationally-recognized as a best-in-class translational pain medicine program, ultimately transforming the way we diagnose and treat painful conditions. He was also instrumental in developing Duke Innovative Pain Therapies, a first-of-its-kind multispecialty pain practice focused on non-opioid therapies, which opened its doors to patients in September 2016. In 2017, Dr. Maixner received one of the highest honors in academia with his appointment as the Joannes H. Karis, MD, Professor of Anesthesiology, designated by the Duke University School of Medicine, becoming only the fifth faculty member in our department to be named a distinguished professor. This endowed professorship recognized his remarkable achievements in advancing medical science, significantly shaping the field of pain research and education, profoundly impacting patient care and exemplifying superior mentorship. That same year, he was named our department’s vice chair for research.

Dr. Maixner was originally from Ottumwa, Iowa. After completing his BA, PhD, and DDS at the University of Iowa, he became a research fellow at the National Institute of Dental Research. He went on to become faculty at UNC-CH, where over the span of 30 years, he served as a professor in the Departments of Endodontics and Pharmacology, co-director of the Oral and Maxillofacial Pain Program, associate dean for academic affairs in the School of Dentistry, and director of the Center for Pain Research and Innovation.

Dr. Maixner played a key role as a knowledge leader in the field of pain; he served as president of the American Pain Society and on our nation’s Health and Human Services Interagency Pain Research Coordinating Committee and the NIH’s Pain Consortium, in which he helped shape the direction of our nation’s national strategies in pain research, education and patient care. He considered chronic pain to be a “hidden epidemic” and proudly campaigned for more research support amongst colleagues, sponsors, health organizations, and congressional committees.

Dr. Maixner earned several accolades throughout his career, including the New York College of Dentistry Distinguished Scientist Award and the Wilbert E. Fordyce Clinical Investigator Award from the American Pain Society. His primary research focus was on biological, environmental and genetic factors involved in pain transmission and modulation. Notably, Dr. Maixner was the principal investigator on the National Institute of Dental and Craniofacial Research’s (NIDCR) $19 million, seven-year OPPERA study to examine pain produced by temporomandibular joint and muscle disorders. In 2012, the NIDCR awarded him and his team an additional $16 million in funding to support the study (called OPPERA II) for an additional five-year period. He published more than 200 manuscripts and book chapters and was continuously funded by the NIH since 1986.

Additionally, Dr. Maixner was appointed as a member of the Foundation for Anesthesia Education and Research Academy of Research Mentors in Anesthesiology. His mentorship skills were evidenced by the success of the numerous students, trainees and mid-career scientists whom he mentored throughout his career.

Dr. Maixner’s legacy of innovation within all three pillars of research, education and patient care will forever be remembered here at Duke as we continue to honor his accomplishments and grow his goals. Most importantly, his legacy will live through his family. He was a dedicated and loving husband to his wife, Viravan, father to his two children, William and Dylan, and grandfather to two granddaughters born earlier this year.

Please join us in extending our sincerest condolences to Dr. Maixner’s family, friends and colleagues. At the request of the family, in lieu of flowers, memorial gifts may be made to our DREAM Campaign in support of research through the DREAM Innovation Grants.

Stacey HiltonIn Remembrance of Dr. William Maixner
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Dr. Terrando Awarded Grant for COVID-19 Related Research

Niccolò Terrando, BSc (hons), DIC, PhDThe National Institutes of Health has awarded Duke Anesthesiology’s Niccolò Terrando, BSc, DIC, PhD, a one-year, $322,620 supplement grant to his R01-funded project, titled “Delirium Superimposed on Dementia Intersects with COVID-19.”

Delirium has become a common complication of COVID-19 that further impairs the recovery of already debilitated patients, in particular older adults. Terrando and his co-investigators are studying the role of neuroinflammation as a putative driver of delirium pathogenesis. For this supplement, they will explore how lung injury, akin to COVID-19 infection, leads to delirium by impairing the blood-brain barrier and triggering immune cell trafficking into the brain.

Terrando aims to develop a model of COVID-19 lung injury that activates the immune system to damage the brain, affecting areas that serve attention, memory, and thinking, and reverse these changes with an experimental drug in development. Findings from this research supplement will address this serious public health concern by providing fundamental knowledge on the pathogenesis of delirium following COVID-19-like infection. Such work has the potential to reduce the health care burden of COVID-19 associated with delirium and related neurologic complications, such as Alzheimer’s disease and related dementias (ADRDs).

“We are thrilled to develop this project in collaboration with Dr. Purushothama Rao Tata in the Duke Department of Cell Biology, an expert in murine lung injury models, and Dr. Harris A. Gelbard in the Center for Neurotherapeutics Discovery at the University of Rochester Medical Center that developed new therapeutics effective in resolving neuroinflammation, which we are currently testing in the R01 funded project,” says Terrando, associate professor in anesthesiology. “We are grateful for the National Institute on Aging’s continuous support, and we are looking forward to providing timely results that may curtail pathologic hallmarks of delirium and neurodegeneration resulting from COVID-19.”

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Dr. Ji Receives Prestigious Award

Ru-Rong Ji, PhD

We are pleased to announce that Dr. Ru-Rong Ji, distinguished professor of anesthesiology, has been selected to receive the prestigious 2020 American Society of Anesthesiologists (ASA) Excellence in Research Award. It recognizes individuals for outstanding achievement in research who has or is likely to have an important impact on the practice of anesthesiology. The individual’s work represents a body of original, mature and sustained contribution to the advancement of the science of anesthesiology. This is only one of two awards presented each year by the ASA to recognize the research accomplishments of members of our specialty.

“Several current and previous members of this department have received this award, and I am very proud to be one of them,” says Ji, chief of basic pain research and co-director of the department’s Center for Translational Pain Medicine (CTPM). “I really appreciate the full support I have received from the department over the last eight years.”

Ji’s work has significant translational potential in almost all areas of pain medicine. He currently serves as the director of the Sensory Plasticity and Pain Research Laboratory. Ji’s research focuses on molecular and cellular mechanisms of chronic pain, including but not limited to mediators of inflammation and pain, neuropathic pain, and cancer pain. He is internationally-recognized for his contributions to demonstrating critical roles of MAP kinase signaling pathways, glial cells, and neuroinflammation in the pathogenesis of chronic pain. His work has demonstrated powerful antinociceptive actions of pro-resolution lipid mediators (e.g., resolvins). His lab has shown that resolvins are among the most potent inhibitors for inflammatory pain and TRP channels. He also determined the down-stream GPCR signaling in macrophages and sensory neurons that mediates the potent actions of these lipid mediators. Recently, Ji’s work has focused on unique neuronal signaling of pattern recognition receptors, such as toll-like receptors (TLRs) and their contribution to pain and itch. And, Ji is notably among the first to establish a connection between mediators of cancer and pain processing showing that tumor cells produce PD-L1 to suppress not only the immune system, but also pain perception permitting cancer growth and metastasis. Ji also has established a broad collaboration with CTPM and Duke University School of Medicine faculty members to develop novel pain therapeutics.

“Dr. Ji is an outstanding scientist and colleague. He has a keen wit and is able to move scientific thought to the next level. Furthermore, he has the ability to implement his thoughts and ideas into productive, high-impact research. He clearly merits this award,” says Dr. William Maixner, vice chair for research and co-director of the CTPM.

Ji lectures internationally and reviews papers for numerous international journals. His research has been published in more than 200 peer reviewed manuscripts in high-impact journals, such as Science and Nature. Ji is one of 54 Duke researchers who made the global list of ‘Highly Cited Researchers’ for 2019; a list he also made in 2018. Ji also serves on editorial boards of Anesthesiology, Pain, Journal of Neuroscience, Neuroscience, and Neuroscience Bulletin. He previously served as an associate professor at Brigham and Women’s Hospital, Harvard Medical School, before joining the Duke faculty in 2012. He earned a PhD in neurobiology at Shanghai Institute of Physiology and completed postdoctoral training at Peking (Beijing) University Medical School, Karolinska Institute, and Johns Hopkins University School of Medicine.

Please join us in congratulating Ji on receiving this well-deserved award.

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