Researcher Awarded Grant to Study the Most Aggressive Cancer

Madan M. Kwatra, PhDAstraZeneca has awarded Duke Anesthesiology’s Madan Kwatra, PhD, a $97,109 grant for his project titled, “Efficacy of AZD9291 against EGFRvIII-positive glioblastoma.”

Glioblastoma (GBM) is a deadly brain cancer, and according to Dr. Kwatra, all attempts to control it have failed so far. GBMs exhibit significant inter- and intratumoral heterogeneity, and to control this type of tumor, he believes a personalized approach is required.

According to the research statement, one target, whose gene is amplified and mutated in a large number of GBMs, is the epidermal growth factor receptor (EGFR). But, all attempts to target it have been unsuccessful. Dr. Kwatra attributes this failure to the extreme molecular heterogeneity of EGFR, as well as to the poor brain penetration of previously tested EGFR-Tyrosine Kinase Inhibitors (EGFR-TKIs). Recently, a third generation EGFR-TKI, known as AZD9291, was reported to have good brain penetration. AZD9291 also blocks EGFRvIII, a mutant EGFR present in 20 percent of GBM tumors, with high affinity. Dr. Kwatra’s preliminary studies (conducted under a collaborative agreement among his laboratory, NIH, and AstraZeneca) indicate AZD9291 is active against EGFRvIII-positive GBMs intracranially transplanted in nude mice.

This study will test if AZD9291’s efficacy against EGFRvIII-positive GBMs can be improved by giving 25mg/kg AZD9291 twice a day. Finally, before conducting studies in GBM patients, Dr. Kwatra will examine whether EGFRvIII-positive GBMs differ in their response to AZD9291. This way the compound is tested only in those GBM patients expressing the sensitive form of EGFRvIII (precision medicine approach).

Dr. Kwatra is an associate professor in anesthesiology and the director of the Molecular Pharmacology Laboratory where researchers focus to understand the role of G protein-coupled receptors in human diseases.

Chris KeithResearcher Awarded Grant to Study the Most Aggressive Cancer
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Dr. Maixner Named President of American Pain Society

William Maixner, DDS, PhDOn March 6, the board of directors elected Duke Anesthesiology’s William Maixner, DDS, PhD, president of the American Pain Society (APS). It’s a multidisciplinary community that brings together a diverse group of scientists, clinicians and other professionals to increase the knowledge of pain and transform public policy and clinical practice to reduce pain-related suffering.

Dr. Maixner, professor in anesthesiology and director of the Center for Translational Pain Medicine (CTPM), is a world-renowned pain researcher who has dedicated his career to unraveling the mysteries of chronic pain. His research focuses on biological, environmental, and genetic factors involved in pain transmission and modulation.

In his new role, Dr. Maixner will help the APS achieve its goal of advancing the care of people in pain by ensuring access to treatment, removing regulatory barriers, increasing funding for pain research and educating practitioners and policy makers in all settings about advances and economics of effective treatment.

“This is a wonderful opportunity to help further shape the society’s activities in the area of pain research and pain management,” says Dr. Maixner. “This is one of the most established pain-oriented societies, and it’s such an honor to be recognized by my peers and to be part of the opportunity to further the mission of the APS which falls in line with the same mission statement that we have at the CTPM at local, state and federal levels for pain patients.”

Dr. Maixner was a key leader in establishing Duke Anesthesiology’s Center for Translational Pain Medicine in January of 2016, which brings together basic scientists, clinicians and clinical researchers who have a common core mission of transforming the way painful conditions are diagnosed and treated. He also helped develop Duke Innovative Pain Therapies, a first-of-its-kind multispecialty pain practice in Raleigh that opened in September of 2016. Learn more about these initiatives in the 2016 edition of the department’s BluePrint magazine.

Chris KeithDr. Maixner Named President of American Pain Society
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Anesthesia Faculty Awarded Health Innovation Grant

Drs. Annemarie Thompson and Madhav SwaminathanThe Duke Institute for Health Innovation (DIHI) has awarded a multidisciplinary team from the Duke departments of anesthesiology, surgery, medicine and statistical sciences a $50,000 grant for their project titled, “PROMISE – Perioperative Risk Optimization with Machine learning for an Improved Surgical Experience.”

The goal of the project is to use machine learning tools to develop risk stratification models using patient level data to predict surgical risk and direct optimization interventions to reduce this risk. The funding will be used to develop risk stratification tools, and help providers in surgery clinics with optimization goals for their at-risk surgical populations.

The team of investigators includes Duke Anesthesiology’s Drs. Annemarie Thompson and Madhav Swaminathan (both of the Cardiothoracic Anesthesia Division), as well as Dr. Mitchell Heflin, Erich Huang, Shelley McDonald, Mark Sendak, Katherine Heller and Dr. Sandhya Lagoo-Deenadayalan.

The mission of the DIHI is to promote transformative innovation in health and health care, and to help cultivate a community of entrepreneurship across Duke University and its health enterprise. Proposed projects address actual and important problems encountered by care providers, patients and their loved ones in the Duke University Health System and represent urgent health challenges nationally.

Chris KeithAnesthesia Faculty Awarded Health Innovation Grant
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Postdoctoral Fellow Receives APS Award

Xin Zhang, PhDThe American Pain Society (APS) has awarded Duke Anesthesiology’s Xin Zhang, MD, PhD, the Young Investigator Travel Award for its 36th Annual Scientific Meeting!

Funding from this award will allow Dr. Zhang the opportunity to travel to Pittsburgh and present his poster abstract, titled “Sustained Activation of β2- and β3ARs Leads to Phosphorylation of Neuronal MAPKs and Activation of Glial Cells in Spinal Cord and DRG.” Co-authors of this project include director of The Nackley Lab, Dr. Andrea Nackley, and undergraduate researchers in the lab, Harrison Ballard and Julia Kozlowski. The APS  acknowledges the National Center for Complementary and Integrative Health (NCCIH) for support of the Young Investigator Travel Award program.

As noted in the abstract, functional pain syndromes, such as fibromyalgia and temporomandibular disorder, are associated with enhanced catecholamine tone and decreased catechol-O-methyltransferase (COMT; an enzyme that metabolizes catecholamines) activity. Consistent with clinical syndromes, The Nackley Lab has shown that sustained 14-day delivery of the COMT inhibitor OR486 in rodents results in pain at multiple body sites that persists for three weeks following OR486 cessation.

Results of this study suggest that treatments targeted towards βAR and MAPK signaling pathways may prove useful in the management of functional pain syndromes.

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.

Chris KeithPostdoctoral Fellow Receives APS Award
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Cooke Nominated for Prestigious Award

10th Annual Susan B. Clark Administrative Leadership AwardThe Duke University School of Medicine named Jaime Cooke, staff assistant for Duke Anesthesiology’s Cardiothoracic Anesthesia Division, as a nominee for the 10th Annual Susan B. Clark Administrative Leadership Award for her exceptional contributions to Duke and the wider community!

This annual award was founded in 2007 to recognize administrative professionals at Duke who demonstrate the qualities exemplified by the late Susan Clark who rose through the ranks at Duke Health, from an entry-level position to strategic services associate in the Office of the Chancellor, and became a role model for all staff.

Cooke is among six colleagues selected as 2016 honorees (finalists) of this award. All honorees are noted for their dedication to Duke, service to others, personal strength of character, and acting as a role model to others. Nominations for this award can be made by any Duke Health employee; Cooke was nominated by Dr. Mihai Podgoreanu, chief of the Cardiothoracic Anesthesia Division.

Honorees were invited to the 10th annual awards luncheon on March 9 at the Doris Duke Center to celebrate the excellence exemplified by the nominees and this year’s winner, Laverne Myers. Chancellor A. Eugene Washington called each honoree to the podium to personally present them with a bound version of their nomination packets.

Chris KeithCooke Nominated for Prestigious Award
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Undergraduate Researcher Awarded Fellowship

Katie KanterDuke’s Summer Neuroscience Program (formerly known as NPR) has awarded Katie Kanter, a researcher with Duke Anesthesiology’s The Nackley Lab, a fellowship for her project, titled “Effects of MOR-1K Genetic Variation on Cellular Activity.”

Opioid-induced hyperalgesia manifests as increased pain sensitivity due to acute or chronic opioid administration. A truncated variant in the mu opioid receptor, MOR-1K, has been linked to pain in human genetic studies, and shown to produce cellular excitation, resulting in hyperalgesia rather than analgesia. The Nackley Lab has identified a candidate single nucleotide polymorphism (SNP) within the enhancer box regulatory motif on MOR-1K exon 13 in CXB7/ByJ mice, that is predicted to contribute to the increased pain sensitivity observed in this variant compared to 129S6 mice.

The proposed work will continue a previously unpublished study by The Nackley Lab to elucidate alterations to MOR-1K receptor function related to this SNP using a cAMP assay, and ultimately examine changes to transcriptional regulation via a luciferase assay.

The Nackley Lab is part of Duke Anesthesiology’s Center for Translational Pain Medicine. The main objectives of this lab’s research include: 1) To determine the factors that put some people, but not others, at risk for maladaptive chronic pain conditions, 2) to elucidate the mechanism(s) whereby genetic, biological, and environmental factors drive chronic pain, and 3) to improve pharmacologic management of pain.

Chris KeithUndergraduate Researcher Awarded Fellowship
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