North Carolina State University
B Duncan X Lascelles BSc, BVSc, PhD, FRCVS, DSAS(ST), DECVS, DACVS
Dr. J. McNeely and Lynne K. DuBose Distinguished Professor of Musculoskeletal Health
Professor of Translational Pain Research and Surgery
Email: [email protected]
Proposed Core Mentor Team:
Margaret E. Gruen, DVM, MVPH, PhD, DACVB. Associate Professor of Behavioral Medicine, NC State College of Veterinary.
Amanda E. Nelson, MD, MSCR, RhMSUS. Associate Professor of Medicine (Internist and Rheumatologist), Thurston Arthritis Research Center, UNC Chapel Hill
Santosh Mishra M.Tech., PhD, Associate Professor of Neurobiology, NC State College of Veterinary Medicine
Liubov Arbeeva MS. Thurston Arthritis Research Center Biostatistician, UNC Chapel Hill
Description of Potential Research Project(s):
The aims of the main project are:
Aim 1: Determine cross-sectional associations between altered intestinal permeability (IP), systemic inflammation, and radiographic and symptomatic MJOA in humans and pet dogs.
Aim 2; Identify biomarkers predictive of development and worsening of MJOA and determine longitudinal associations with markers of systemic inflammation and IP among humans and dogs.
Aim 3; Test the effects of a prebiotic on IP, the microbiome and MJOA symptoms in a cohort of pet dogs.
These studies will both verify the association between increased IP and MJOA and robustly define biomarkers predictive of development and worsening MJOA, laying the groundwork for mechanistic studies to understand how increased IP promotes MJOA and to identify therapeutic targets, as well as provide means to identify at-risk individuals for preemptive management.
Additional work layered onto this will be to capture data on cognitive function and affective state in the population of ~175 dogs that will include individuals without OA, with single joint OA and pain, and with a range of multijoint OA and pain burden and severity. This will allow cognitive function and affective state data to be evaluated against a comprehensive battery of pain, sensitivity and functional data, as well as serum biomarkers. This novel work will form the basis of subsequent grant submissions.
Other opportunities for translational OA research experience:
• Verification of the utility of blockade of the VEGF 1 and VEGF2 receptors to treat OA pain and alter disease progression. This work involves mouse and rat models, and induced OA in research dogs.
• Elucidating the role of artemin/GFRa3 signaling in OA pain. This project involves mouse OA models and naturally occurring OA in pet dogs.
Veterinary specialists appropriate for this research opportunity:
Internal Medicine, Behavior, Anesthesia and Analgesia, Neurology, Surgery, Radiology
Additional Training Opportunities:
In addition to the comprehensieve translational research training that will occur, the fellow will be expected to participate in:
• Weekly lab meetings in the Lascelles and Gruen labs
• Twice monthly journal clubs
• Presentation opportunities at: Thurston Arthritis Research Center (TARC) Research Day; NC State CVM Research Forum; Veterinary Specialist Scientific Meeting (e.g. ACVB; ACVS)
• Seminars: TARC research and clinical seminars (UNC, monthly); International Association for the Study of Pain webinars (online repository of webinars, faculty and trainees); Comparative Pain
Research and Education Center seminars (planned, monthly); Duke Anesthesiology pain research seminars (~monthly)
• Rounds: (select) speciality service rounds (NC State, weekly); clinical rheumatology rounds (UNC Chapel Hill School of Medicine)
Diversity and Inclusion seminars: e.g. National Coalition Building Institute and the Project SAFE workshops at NC State
• NC State College of Veterinary Medicine K-Award Preparation: Seminars and Workshops (year round)