Beverley Greenwood-Van Meerveld, PhD

Greenwood

Appointments:

  • Professor of Physiology 
  • Director Oklahoma Center for Neuroscience 
  • Presbyterian Health Foundation Chair in Neuroscience 
  • President’s Associates Presidential Professor
  • Adjunct Professor of Pharmaceutical Sciences
  • Adjunct Professor of Psychiatry & Behavioral Sciences
  • Senior VA Career Scientist
  • PRESIDENT American Neurogastroenterology and Motility Society

Special lnterests:

  • 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.

    Training:
  • 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) 

Research Summary:

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:

1. 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)

2. 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) 

3. 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

4. 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

Recent Publications (from a total of 119 peer reviewed publications, 19 invited reviews, 18 book chapters and 9 US patents) 

Recent Publications (2015-2018) 

  • Johnson AC, Ligon C, Latorre R, Greenwood-Van Meerveld B. (2018) Optogenenetic Activation of Amygdaloid Circuitry Induces Visceral Pain in Freely Moving Male Rats. Am. J Physiol. 314(3):G448-G457 
  • Greenwood-Van Meerveld B. Mohammadi E, Latorre R, Edward Truitt, J.D., Gregory Jay, Benjamin Sullivan, Tannin Schmidt, Nataliya Smith, Debra Saunders, Jadith Ziegler, Megan Lerner, Robert Hurst, and Rheal A. Towner (2018). Intravesical Recombinant Human Proteoglycan 4 (rhPRG4) as a Novel Potential Therapy for Chronic Bladder Pain and Irritable Bowel Syndrome. Urology 116:230.e1-230.e7.  
  • Mohammadi E, Ligon C, Ge P, Hannig G, Higgins C, Greenwood-Van Meerveld B (2018).Linaclotide Attenuates Visceral Organ Crosstalk: Role of Guanylate Cyclase C Activation in Reversing Bladder-Colon Cross Sensitization.  J. Pharm. Exp. Therap. 366(2):274-281.
  • Ligon C, Mohammadi E, Ge P, Hannig G, Higgins C, Greenwood-Van Meerveld B (2018).Linaclotide Inhibits Colonic and Urinary Bladder Hypersensitivity in Adult Female Rats Following Unpredictable Neonatal Stress. Neurogastroenterol. Mot. May 24:e13375. doi: 10.1111/nmo.13375. [Epub]  
  • Eidam Hilary Schenck, John Russell, Kaushik Raha, Donghui Qin, Huiping Amy Guan, Zhiliu Zhang, Gong Zhen, Haiyu Yu, Chengde Wu, Yan Pan, Sylvie Laquerre, Sharon Robinson, Angela White, Amanda Giddings, Karl Tyler, Ehsan Mohammadi, Beverley Greenwood-Van Meerveld, Allen Oliff, Sanjay Kumar, Mui Cheung (2018). Discovery of a first-in-class potent, selective, and gut-restricted RET kinase inhibitor GSK3179106 as a clinical candidate for the treatment of Irritable Bowel Syndrome. ACS Med Chem Lett. 24;9(7):623-628.  
  • Hattay P, Prusador D, Johnson AC,  Greenwood-Van Meerveld B (2018). Stereotaxic exposure of the Central Amygdala to Corticosterone Increases Colonic permeability in the rat. Frontiers in Physiology (in press)  
  • Russell JP, Mohammadi E, Ligon C, Latorre R, Johnson AC, Gershon MD, Rao M, Joberty G, Zinn N , Hoang B,Krull D, A. Ho W.-Y M, Eidam HS, DeMartino MP, Cheung Mui, Oliff A, Greenwood-Van Meerveld B, Kumar S. (2018). Enteric RET Inhibition Stimulates Intestinal Secretion via Cholinergic Signaling in Rat Colonic Mucosal Preparations. Neurogastroenterol. Mot. (in press)
  • Mohammadi E, Pietra C, Giuliano C, Li F, and Greenwood-Van Meerveld, B. (2018). Attenuation of Visceral and Somatic Nociception by Administration of Ghrelin Agonists. J. Pharmacol. Exp. Ther. (in press)
  • Russell JP, Mohammadi E, Ligon C, Latorre R, Johnson AC, Gershon MD, Rao M, Joberty G, Zinn N , Hoang B,Krull D6, A. Ho W.-Y M, Eidam HS, DeMartino MP, Cheung Mui, Oliff A, Kumar S, Greenwood-Van Meerveld B. (2018). Exploring the Potential of RET Kinase Inhibition for Irritable Bowel Syndrome: A Preclinical Investigation in Rodent Models of Colonic Hypersensitivity. J. Pharmacol. Exp. Ther. (in press)
  • Prusator DK, Greenwood-Van Meerveld B. (2017) Amygdala-Mediated Mechanisms Regulate Visceral Hypersensitivity in Adult Females following Early Life Stress: Importance of Glucocorticoid Receptor and Corticotropin-Releasing Factor. Pain 158:296-305
  •  Hattay P, Prusator DK, Tran L, Greenwood-Van Meerveld B. (2017) Psychological Stress-Induced Colonic Barrier Dysfunction: Role of Immune-Mediated Mechanisms. Neurogastroenterol. Mot29(7) e13043
  • Yang, Q., Xia, D., Towner, R.A., Smith. N., Saunders, D., Fung, K.-M., Aston, C.E., Greenwood-Van Meerveld, B., Hurst, R.E., Madihally, S.V., Kropp, B.P., Lin, H.-K. (2017) Reduced urothelial regeneration in rat bladders augmented with permeable porcine small intestinal submucosa assessed by magnetic resonance imaging. J. Biomed. Mater. Res. 106(5):1778-1787. 
  • Mohammadi E, Prusador D, Healing E, Hurst R, Towner R, Wisniewski AB, Greenwood-Van Meerveld B. (2016) Sexually Dimorphic Effects of Early Life Stress on Bladder Contractility in Adulthood.  Biology of Sex Differences 7:8 pages 1-10.
  • Towner RA, Wisniewski, AB, Wu DH, Van Gordon SB, Smith N, North JC, McElhaney R, Aston CE, Shobeiri A, Kropp BP, Greenwood-Van Meerveld B., Hurst RE. (2016) Feasibility of using Clinical Contrast-Enhanced MRI to Quantify Bladder Permeability Associated with Interstitial Cystitis J. Urol. 195(3):631-8.
  • Ligon CO, Moloney RD, Greenwood-Van Meerveld B. (2016) Targeting Epigenetic Mechanisms for Chronic Pain: A Valid Approach for the Development of Novel Therapeutics. Invited Mini Review J. Pharm. Exp. Therap. 357(1):84-93.
  • Greenwood-Van Meerveld B, Moloney RD, Johnson AC, Vicario M.  (2016) Mechanisms of stress-induced visceral pain: implications in irritable bowel syndrome. J. Neuroendocrinology (in press).
  • Hurst R, Van Gorden S, Tyler K, Mohammadi E, Kropp B, Towner R., Lin HK, Marentette J, McHowat J, Greenwood-Van Meerveld B. (2016) In the Absence of Overt Urothelial Damage, Chondroitinase Digestion of the GAG Layer or Neutralization with Dilute Protamine Sulfate Increases Bladder Permeability in Rats. Am. J. Physiol (in press).
  • Prusador D, Greenwood-Van Meerveld B. (2016) Comparison of Nociceptive Behaviors in Adult Rats Following Three Early Life Stress Paradigms. Biology of Sex Differences (in press).
  • Prusador D, Greenwood-Van Meerveld B. (2016) Sex Differences in Stress-Induced Visceral Hypersensitivity Following Early Life Adversity: A Two Hit Model.  Neurogastroenterol. Mot(in press).
  • Latorre R, Sternini C, De Giorgio R, Greenwood-Van Meerveld B. (2016)Enteroendocrine Cells: A Review of Their Role In Brain-Gut Communication.  Neurogastroenterol. Mot. (in press).
  • Vanner S, Greenwood-Van Meerveld B, Mawe GM, Shea-Donohue T, Verdu E, Wood J and Grundy D. (2016) Fundamentals of Neurogastroenterology: Basic Science. Gastroenterology (in press).
  • Prusador D, Andrews A, Greenwood-Van Meerveld B. (2016) Neurobiology of Early Life Stress and Visceral Pain: Translational Relevance From Animal Models to Patient Care. Neurogastroenterol. Mot. (in press).
  • Greenwood-Van Meerveld B. Prusador D, Johnson AC. (2015) Animal Models of Visceral Pain: Pathophysiology Translational Relevance and Challenges (Invited Review).  Am. J. Physol. 308 (11):G885-903.
  • Johnson AJ, Tran L, Greenwood-Van Meerveld B. (2015) Knockdown of Corticotropin- Releasing Factor in the Central Amygdala Reverses Chronic Hyperalgesia.Translational Psychiatry  93:116-123. 
  • Johnson AJ and Greenwood-Van Meerveld B. (2015) Knockdown of steroid receptors in the central nucleus of the amygdala induces heightened pain behaviors in the rat. Neuropharmacology 9:116-23.
  • Towner RA, Smith N, Saunders D, Van Gordon SB, Wisniewski AB, Tyler K, Greenwood-Van Meerveld B., Hurst RE. (2015) Contrast-Enhanced Magnetic Resonance Imaging (CE-MRI) as a Diagnostic Tool for Assessing Bladder Permeability and Associated Colon Cross-Talk: Pre-Clinical Studies in a Rat Model. J. Urol. 193 (4):1394-400.
  • Prusador D, Greenwood-Van Meerveld B. (2015) Gender Specific Effects of Neonatal Limited    Nesting on Viscerosomatic Sensitivity and Anxiety-Like Behavior in Adult Rats.  Neurogastroenterology and Motility 27 (1):72-81.

http://find.ouhsc.edu/Faculty.aspx?FacultyID=183

Current Funding

[1]        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

[2]        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

[3]        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 forpainful
            bladder syndrome

[7]        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.

[8]        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

[9]        Agency: Ironwood                                                                   

            Title:  Development of rat model of chronic viscero-somatic pain induced by
             early life stress

             Role PI: Beverley Greenwood-Van Meerveld
​        
[10]      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

[11]      Agency: TEVA-2

            Title: Preclinical Investigation of A New Compound for the Treatment of Visceral Pain

             Role PI: Beverley Greenwood-Van Meerveld

Contact:

Office telephone: (405) 456-3547
Email: Beverley-Greenwood@ouhsc.edu