Beverley Greenwood-Van Meerveld, PhD

George Lynn Cross Research Professor Emeritus

President’s Associates Presidential Professor

University of Oklahoma Health Sciences Center

Senior VA Career Scientist (Retired)

405-456-3547

Beverley-Greenwood@ouhsc.edu

In my capacity as a Professor of Physiology, Director of the Oklahoma Center for Neuroscience (OCNS), Presbyterian Health Foundation Endowed Chair in Neuroscience, President’s Associates Presidential Professor and Senior VA Career Scientist at the University of Oklahoma Health Sciences Center (OUHSC), I am actively involved in research currently serving as the PI on two active VA Merit grants, an OCAST grant and PI on multiple industry-sponsored contracts. I have an extensive publication record with numerous original publications, scientific reviews, book chapters and research patents.

My research team of highly motivated post-doctoral fellows, students and research associates are conducting innovative research in neurogastroenterology with a long-term research objective of understanding how the brain regulates the gastrointestinal (GI) tract. I have an international reputation and a proven track record with over 30 years of research experience. My work is fully supported by continuous grant support from federal agencies, foundations and industry. In May 2004 I was awarded the prestigious Janssen Award for Basic Research in Digestive Diseases, in 2006 I received a VA Career Scientist Award for my research and in 2016 was promoted to a Senior VA Career Scientist (2016-2023). In 2012, I received the OU Reagents Award for Superior Research and Creative Activity and in 2017 I was awarded the President’s Associates Presidential Professor at OUHSC (2017-2023). My primary research interest focuses on the central nervous system regulation of visceral pain with a strategic objective of using preclinical (in vivo and in vitro) rodent models and multiple state-of-the-art techniques, from molecular and cellular to behavioral, pharmacological and electrophysiological methods to address a series of key and important questions that will advance basic scientific knowledge and have direct relevance to the diagnosis and treatment of veterans with functional GI disorders.

Currently my laboratory is focused around the following themes:

Central Neural Circuitry Underlying Anxiety and Visceral pain: Mechanisms of Resilience and Novel Treatments: In one aspect of my research we are studying the neuroanatomical and neuropharmacological substrates involved in the interaction between visceral pain and anxiety. Specifically, my research focuses on the role of amygdala-mediated mechanisms in the control of visceral and somatic pain and the mechanisms connecting anxiety and visceral (colonic) hypersensitivity. We are attempting to identify at least one potential neural substrate that might be involved in the central processing of visceral pain. From there we hope to identify a receptor mechanism within the neural substrate that mediates central processing of visceral pain. A long-term goal is to investigate how the neural substrate modulates visceral pain sensitivity within the larger neural pathway controlling anxiety, and use this knowledge identify potential pharmacotherapeutic targets in the central processing pathway that mediates visceral pain. We have demonstrated long lasting increases in anxiety-like behavior and viscerosomatic sensitivity in response to the local exposure of the amygdala to CORT. We found persistent down-regulation of GR expression and increases in the expression of CRF and HCN1 channels leading to hyper-excitability of the CeA neurons. These changes in gene expression represent a potential mechanism leading to chronic anxiety and pain, via facilitation of the HPA axis. The objective of recent experiments has been to use gene knockdown to directly manipulate CRF and GR expression in the central amygdala. We demonstrated that knockdown of CRF within the amygdala inhibited stress induced chronic visceral and somatic pain, and that loss of GR within the amygdala regulation is key to triggering visceral and somatic pain. Such findings are relevant for the future development of gene targeted therapeutics to treat stress-induced visceral and somatic pain. (Funded by the Department of Veteran’s Affairs: 2013-2017; 2018-2022)
Early life stress on visceral and somatic pain in adulthood: Sex differences. We are focused on understanding how ovarian hormones cause sex differences in visceral pain in response to various forms of adverse early life stress (ELS). Our latest project is to investigate the mechanisms by which the context of the ELS can affect nociception in adulthood. It is our hypothesis that a conditioning model of ELS will provide useful information on the process and mechanisms by which acute ELS leads to life-long increase in visceral and somatic sensitivity especially in females (Funded by the Department of Veteran’s Affairs: 2011-2015 and renewed 2015-2019)
Visceral organ cross communication: We are studying the mechanisms of visceral organ cross-sensitization and the role of central and peripheral neuronal plasticity to understand the overlap between IBS and chronic pelvic pain disorders. Our ongoing studies are manipulating bladder permeability to determine whether there is an effect on the colon (Funded by National Institutes of Health P20: 2012-2014). Pending NIH grant
Mechanisms of Neuronal Sensitization: Through a collaboration with Dr. Ken Miller, OSU we are investigating the spinal mechanisms of sensitization following colonic inflammation (Funded by Oklahoma Center for the Advancement of Science and Technology:2016-2019)

5. Development of novel pharmacological approaches: I have many years of collaborative research with industry partners to identify novel drugs to treat GI disorders such as Irritable bowel syndrome, inflammatory bowel disease and post-operative ileus.

In my capacity as Professor of Physiology and Director of the Oklahoma Center for Neuroscience at OUHSC I am involved in student education, curriculum development and the professional growth of the graduate students. I currently teach and serve as the course-director for the multiple graduate courses and in 2014 was inducted into the OUHSC College of Medicine Academy of Teaching Scholars.

Course Director, Current Topics in Neuroscience, Advanced Graduate School Course, OUHSCCourse Director, Neuroscience Journal Club, Advanced Graduate School Course, OUHSC
Course Director, Neuroscience Selective: Neuroimmunology, OUHSC
Course Director, Physiology Selective: Smooth Muscle, OUHSC

Education:

BSc. with Special Honors: Physiology, University of Sheffield, U.K. (1977-80)
Ph.D. GI Neurophysiology, University of Sheffield, U.K. (1980-83)
Alberta Heritage Postdoctoral Research Fellow Gastrointestinal (GI) Research, University of Calgary, Canada (1983-86)

Clinical/Research Interests:

To advance the science and understanding of brain-gut interactions by the best possible research.
Pursuing interdisciplinary synergistic collaborations to take advantage of cutting edge technologies, and innovative research approaches to treat gastrointestinal disorders such as irritable bowel syndrome, post-operative ileus and gastroparesis.

My research was fully supported by continuous grant support from federal agencies, foundations and industry until my retirement in 2021. At the time of my retirement I was actively involved in research serving as the PI on an active NIH R01 grant, a VA Merit grant, an OCAST grant and PI on multiple industry-sponsored contracts. I have an extensive publication record with numerous original publications, scientific reviews and book chapters. In May 2004 I was awarded the prestigious Janssen Award for Basic Research in Digestive Diseases. In 2006 I received a VA Career Scientist Award for my research and in 2016 was promoted to a Senior VA Career Scientist (2016-2023). In 2012, I received the OU Reagents Award for Superior Research and Creative Activity, in 2017 I was awarded the President’s Associates Presidential Professor at OUHSC and in 2020 I was awarded the prestigious George Lynn Cross Professor of Research at OUHSC. After retirement, I serve as the Chair of a VA Research Merit Review Panel (NURP), ad hoc member of an NIH study section and in Jan 2022 I will serve as the Editor in Chief of the Journal of Pharmacology and Experimental Therapeutics for 3 years. May 2022 I will be receive a prestigious Research Mentor Award, from the Neurogastroenterology and Motility section of the AGA Institute.

Funding:

Agency: Department of Veterans Affairs. Senior Research Career Scientist Award
Role: PI Beverley Greenwood-Van Meerveld
Specific Objective: This award provides salary support [partial VA component] to Dr. BGVM
Agency: Department of Veterans Affairs. Gulf War Merit Review Grant
Title: Understanding Pain of Gastrointestinal Origin in Women that Serve in OEF/OIF
Role: PI Beverley Greenwood-Van Meerveld
Specific Objective: This project investigates the mechanisms underlying the link between stress and behaviors that impact the health and overall quality of life of female Veterans
Agency: NIH Phase 1 SBIR Project:
SuperGAGs for Intravesicular Treatment of Interstitial Cystitis
Role: OUHSC PI Beverley Greenwood-Van Meerveld (Glycologix, LLC)
Specific Objective: This project investigates a novel treatment approach for painful bladder syndrome
Agency: OCAST
Title: Central Epigenetic Reprogramming of Amygdala Receptor Expression in Stress-Induced Chronic Pain
Role: PI Beverley Greenwood-Van Meerveld
Specific Objective: This project investigates the epigenetic mechanisms within the amygdala involved in chronic stress-induced pain.
Agency: Department of Veterans Affairs. Merit Review Grant
Title: Central Mechanisms Modulating Visceral Hypersensitivity 1I01BX002188-01
Role: PI Beverley Greenwood-Van Meerveld
Specific Objective: This project investigates the effect of amygdala activation on GI function
Agency: Ironwood
Title: Development of rat model of chronic viscero-somatic early life stress
Role PI: Beverley Greenwood-Van Meerveld
Agency: Lubris
Title: A study to determine the potential of recombinant lubricin as a new therapy for IBD/colitis in rodent models
Role PI: Beverley Greenwood-Van Meerveld
Agency: TEVA-2
Title: Preclinical Investigation of A New Compound for the Treatment of Visceral Pain
Role PI: Beverley Greenwood-Van Meerveld

Select Honors and Accomplishments:

Past-Chair, Neuropharmacology Division, American Society for Pharmacology & Experimental Therapeutics (ASPET)

Past President, American Neurogastroenterology and Motility Society

Director, American Neurogastroenterology and Motility Society Institute

Editor-Elect Journal of Pharmacology and Experimental Therapeutics

Specialty Chief Editor: Abdominal and Pelvic Pain, Frontiers in Pain Research

Joint Chair, Rome V: Fundamentals of Neurogastroenterology: Basic Science

Select Publications:

Select Publications in 2021 from a total of 165 papers, 26 invited reviews and 20 book chapters

Towner RA, Greenwood-Van Meerveld B. Mohammadi E, Saunders D, Smith N, Sant GR. Shain HC, Jozefiak TH, Hurst RE (2021). SuperGAG Biopolymers for Treatment of Excessive Bladder Permeability. Pharmacology Research & Perspectives (in press)

Ligon C, Hannig G, Greenwood-Van Meerveld B. (2021) Peripheral Guanylate Cyclase-C Modulation of Corticolimbic Activation and Corticotropin Releasing Factor Signaling in a Rat Model of Stress-induced Colonic Hypersensitivity. Neurogastroenterology and Motility (in press)

Rheal Towner, Debra Saunders, Megan Lerner, Robert Silasi Mansat, Tian Yuan, Dylan Barber, Janet Faakye, Adam Nyul-Toth, Anna Csiszar, Greenwood-Van Meerveld B. , Nataliya Smith. Temporary Opening of the Blood-Brain Barrier with the Nitrone Compound OKN-007. American Journal of Nuclear Medicine and Molecular Imaging. (in press)

Yuan T, Greenwood-Van Meerveld B. (2021) Amygdala microglia modify neuronal plasticity via complement C1q/C3-CR3 signaling and contribute to chronic stress-induced visceral pain. Am J. Physiol. (in press)

Orock AM, Louwies T, Ligon CO, Mohammadi E, Greenwood-Van Meerveld B. (2021) Environmental Enrichment Prevents Stress-Induced Epigenetic Changes in the Expression of Glucocorticoid Receptor and Corticotrophin Releasing Hormone in the Central Nucleus of the Amygdala to Inhibit Visceral Hypersensitivity. Experimental Neurology (in press)

Louwies T, Orock A, Johnson AC, Greenwood-Van Meerveld B. (2021) Stress-induced visceral pain in female rats is associated with epigenetic remodeling in the central nucleus of the amygdala. Neurobiology of Stress (in press)

Mohammadi E, Ligon, Mackenzie K, Stratton J, Shnider, Greenwood-Van Meerveld B. (2021) Importance of CGRP-Mediated Mechanisms in Stress-induced Colonic and Bladder Hypersensitivity. J. Pharmacol. Exp. Ther(in press)

Towner R, Saunders D, Lerner M, Mansat RS, Yuan T, Barber D, Faakye J, Nyul-Toth A, Csiszar A, Greenwood-Van Meerveld B, Smith N. Temporary Opening of the Blood-Brain Barrier with the Nitrone Compound OKN-007. Am J. of Nuclear Medicine and Molecular Imaging (in press)

Yuan T, Orock A, Greenwood-Van Meerveld B. (2021) Enriched Environment Reduces Chronic Stress-Induced Visceral Pain By Modulating Microglial Activity in the Central Nucleus of the Amygdala. Am. J. Physiol. (in press)

Louwies T, Greenwood-Van Meerveld B. (2021) Pharmacology of Visceral Pain. Comprehensive Pharmacology (in press)

Tian Y, Greenwood-Van Meerveld B. (2021) Abdominal and Pelvic Pain: Current Challenges and Future Opportunities. Frontiers in Pain Research. (in press)

http://profiles.ouhsc.edu/display/73386

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