Dr. Terrando to Study the Role of the Blood-Brain Barrier

Niccolò Terrando, BSc (hons), DIC, PhDReservoir Neuroscience, Inc, has awarded Duke Anesthesiology’s Niccolò Terrando, PhD, an $80,143 grant to study Therapies to Protect the Blood-Brain Barrier After Surgery.” The project will evaluate the efficacy of Reservoir’s experimental compounds to protect the blood-brain barrier and prevent cognitive deficits and delirium-like behavior following orthopedic surgery. Designed as a pre-clinical academic-industry collaboration, this study has the potential to advance novel, first-in-kind treatments to improve debilitating patient outcomes in postoperative neurocognitive disorders (PND) – an unmet disease area.

Surgeries, including cardiac and orthopedic, often cause neurological complications, such as post-operative delirium and cognitive decline. These outcomes can be severely debilitating and in older adults, can create risk for onset of chronic dementia. It is not yet known how delirium and PNDs develop, or how to effectively treat this complication.

The Neuroinflammation and Cognitive Outcomes Laboratory at Duke Anesthesiology, directed by Terrando, has developed models to study the pathogenesis of postoperative delirium and strategies to combat it. In particular, the investigators have focused on the role for surgery-induced systemic inflammation in causing breakdown of the blood-brain barrier (BBB), a critical interface between the periphery and the central nervous system that regulates brain homeostasis to enable proper functioning. The BBB is often impaired in aging and neurologic disorders, such as epilepsy and Alzheimer’s disease. They have described changes in the BBB following orthopedic surgery, suggesting that opening of this barrier enables immune cells (like monocytes) and molecules (like fibrinogen) to access the brain and trigger pathological disease outcomes. This vascular pathology is especially evident in the context of neurodegeneration as they have described in a recent study published in Alzheimer’s and Dementia.

“The role of the blood-brain barrier in conditions like delirium is just starting to emerge. We are thrilled for this opportunity to work with Reservoir Neuroscience to test novel therapeutics that have the potential to heal the blood-brain barrier and hopefully prevent delirium,” says Terrando, associate professor in anesthesiology.

Reservoir Neuroscience, Inc, is developing new drugs to treat BBB dysfunction. These experiments are designed to provide proof-of-concept of a novel approach to improve outcomes in a rodent model of orthopedic surgery.

Stacey HiltonDr. Terrando to Study the Role of the Blood-Brain Barrier
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Dr. Ji Named CTPM Director

Ru-Rong Ji, PhDWe are pleased to announce that Ru-Rong Ji, PhD, distinguished professor of anesthesiology in the Duke University School of Medicine, has been named the director of Duke Anesthesiology’s Center for Translational Pain Medicine (CTPM). This appointment comes after Ji’s three years of service as co-director of the center, a position he served in alongside the late William “Bill” Maixner, DDS, PhD.

The CTPM launched in January of 2016, further expanding our department’s clinical and research program in innovative pain therapies by bringing together, under one umbrella, leading basic scientists, clinicians and clinical researchers with the core mission of unraveling the causes of painful conditions to improve patient care. The center recently received the rare and prestigious designation as a National Center of Excellence through an $8.5 million National Institutes of Health Program Project Grant (PPG), the first PPG in 40 years awarded to our department.

Ji joined the Duke faculty in 2012 and is one of our department’s most distinguished faculty. His research career, ultimately spanning three continents, has focused on the molecular basis of pain. His work has significant translational potential in almost all areas of pain medicine. Ji 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. He also serves as the director of the Sensory Plasticity and Pain Research Laboratory. Among his many accolades, Ji was awarded the prestigious 2020 American Society of Anesthesiologists Excellence in Research Award and was once again named among the most “Highly Cited Researchers” in the world – one of just 22 faculty from the Duke University School of Medicine to make the 2020 list.

Before arriving at Duke, Ji served as an associate professor at Brigham and Women’s Hospital, Harvard Medical School. 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 extending congratulations to Ji on his new role in our department. As we look forward to Ji advancing the mission of the CTPM, we remain deeply indebted to Dr. Maixner for his innovative vision of the center – a vision which through his extraordinary leadership and mentorship, he brought to fruition at Duke and is now internationally-recognized as a best-in-class translational pain medicine program.

Stacey HiltonDr. Ji Named CTPM Director
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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 in 2020. Please join us in extending our sincerest condolences to Dr. Maixner’s family, friends and colleagues.

To ensure that Dr. Maixner’s legacy is preserved, memorial gifts may be made to the William Maixner Gift Fund to establish a professorship in his name at the Duke University School of Medicine. This highly-coveted, permanently named memorial will honor his exceptional achievements, fuel scientific discovery, and invest in teaching and mentoring the next generation of leaders, providing an extraordinary opportunity to make a difference and to invest in his legacy of excellence.

Updated May 25, 2021

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.”

Stacey HiltonDr. Terrando Awarded Grant for COVID-19 Related Research
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Duke Anesthesiology Awarded Program Project Grant

The National Institutes of Health (NIH) has awarded Duke Anesthesiology a five-year, $8,566,593 million Center of Excellence award that is supported via the NIH’s Program Project Grant (PPG) mechanism. This is of substantial significance to the department and university because it marks the funding of a new national center and represents the first PPG to the department in 40 years.

The designation as a Center of Excellence within Duke Anesthesiology’s Center for Translational Pain Medicine (CTPM) by the National Center for Complementary and Integrative Health (NCCIH) brings this department both national and international recognition; there are only 1-3 Centers of Excellence funded as PPGs by NCCIH in the country. The new center represents a new and unique resource to investigators world-wide who have interest in translational pain research; it represents a nidus that not only advances Duke Anesthesiology’s mission in translational pain research, but brings it increased visibility in the pain field, which will further expand international collaboration and increase its value and recognition as a leader in translational pain medicine.

William Maixner, DDS, PhDWe want to sincerely thank everyone who helped drive the Center of Excellence initiative that has resulted in this extraordinary outcome. This award and designation is the culmination of a nearly three-year effort by the CTPM, initiated by the center’s co-directors, including Dr. William Maixner, who worked closely to develop the proposal with the center’s members and affiliates (*see complete list of names below).

The title of the PPG is “Resolution of Neuroinflammation and Persistent Pain by Complementary Approaches.” The overarching aims of the PPG is to identify new and novel complimentary approaches to the treatment of pain conditions. The PPG will support the intellectual development of the Center of Excellence and the infrastructure for three scientific projects and three support cores. These units will further bring together Duke Anesthesiology’s basic science and clinical groups to advance translational pain research.

*P01 collaborators: William Maixner, Shad Smith, Andrey Bortsov, Andrea Nackley, Sven-Eric Jordt, Niccolo Terrando, Luis Ulloa (Anesthesiology), Wolfgang Liedtke and Yong Chen (Anesthesiology and Neurology), Fan Wang (Neurobiology), and Staci Bilbo (Psychology and Neuroscience)

Stacey HiltonDuke Anesthesiology Awarded Program Project Grant
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