Purmessur Spinal Therapeutics Laboratory
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The Spinal Therapeutics Laboratory (STL) is a Biomedical Engineering research group at The Ohio State University led by Dr. Devina Purmessur that specializes in studying low back pain (LBP). We focus on understanding the biochemical, biomechanical, and cellular mechanisms underlying pathophysiology in discogenic back pain with translation from 2D to 3D and in vivo models.
Research
Low Back Pain
Chronic low back pain (LBP) is one of the leading musculoskeletal disorders associated with years lived with disability and generates annual healthcare costs over $100 billion in the US alone. According to the National Institute of Health(NIH), the magnitude of burden from LBP has grown worse in recent years. In 1990, a study ranking the most burdensome conditions in the U.S. in terms of mortality or poor health as a result of disease put LBP in sixth place; in 2010, LBP jumped to third place with only ischemic heart disease and chronic obstructive pulmonary disease ranking higher.
Intervertebral Disc Degeneration
Lumbar intervertebral discs (IVD) have been implicated in the pathogenesis of LBP. The onset of IVD degeneration can be caused by genetic precursors, acute injury, occupational factors, or simply age. Painful disc disease is characterized by a loss of structural integrity and function, a decrease in cellularity, and high levels of pro-inflammatory cytokines. However, current treatment strategies are highly invasive with poor surgical outcomes and fail to target the underlying disease pathology and aberrant cell biology.
Spinal Therapeutics Lab Research
STL strives to further IVD research in order to develop diagnostic tools and minimally invasive treatments of IVD degeneration. The identification of disc degeneration and pain biomarkers is crucial for the diagnosis of LBP source. Minimally invasive treatments allow better patient outcomes through faster recovery, shorter hospitalization periods and most importantly reduced damage to adjoining tissue.
Investigation is done through the development of in vitro 2D and 3D models that allow the control of the biochemical, mechanical and matrix microenvironment. These models help the testing of established hypotheses and lead to the development of new questions that fuel research.
Current Projects
Cellular Reprogramming
Stem cell therapy and engineered Intervertebral Discs have been proposed to treat IVD degeneration. However, there are caveats with such techniques. Pro-anabolic approaches have been proposed such as viral gene editing, however, viral transfections can cause mutagenesis and immune rejection. Our work
used novel nanotechnology and engineered vesicles to deliver "healthy" factors into diseased intervertebral disc cells on the cellular and tissue level to reprogram disease cells back to a native phenotype both ex vivo and in vivo.
Funding Sources:
Immune Modulation
Intervertebral disc degeneration (IVD) is mediated in part by increases in pro-inflammatory cytokines and infiltration of immune cells. The chronic presence of these cells in the IVD perpetuates a cycle of catabolic activity, driving extracellular matrix degradation, angiogenesis and neoinnervation. Furthermore, these functional changes in the disc environment have been implicated as a driving source of neuronal plasticity and discogenic back pain. Elucidating the role of immune cells in the disc is vital to therapeutically target degeneration and neuropathic pain due to pathophysiological changes within the disc.
Funding Sources:
Cartilage Endplate Calcification
The intervertebral disc is the largest avascular structure in the human body and relies primarily on diffusion of nutrients and waste across the cartilage endplate to remain viable. The health of the cartilage endplate is vital in this, as disc degeneration is highly associated with occlusion of the cartilage endplate; this hinders nutrient and waste transport, which can propagate degenerative changes in the disc and can reduce the effectiveness of therapies that heal or regenerate disc tissue. The mechanisms by which this occurs are still being explored; one major mechanism is calcification of the endplate. In our lab, we are exploring what factors contribute to endplate calcification and its association with endplate cell phenotype. We currently use cell cultures to elucidate biological pathways involved in endplate calcification and aim to validate these pathways using transgenic in vivo models. We utilize histological staining, gene and protein expression assays, and are exploring the use of imaging and analytical compositional techniques to study these phenomena
Funding Sources:
Lab Members
Devina Purmessur, PhD
BS (Honors): Medical Biochemistry, University of Sheffield UK
MS (with Distinction): Immunology and Allergy, University of Nottingham UK
PhD: Molecular Pathology, University of Manchester UK
Postdoctoral training: Spine Bioengineering labs of Dr James Iatridis, University of Vermont and Icahn School of Medicine at Mount Sinai NYC, USA
My research training and diverse scientific background in musculoskeletal pathophysiology has provided me with a unique experimental skill set – combining cell, molecular and immune biology with biomedical engineering that enables me to investigate highly translational questions and mechanisms while grounded in fundamental basic science. I am currently an Early Stage Investigator/ New Investigator Assistant Professor (Tenure track) in the Departments of Biomedical Engineering and Orthopaedics at the Ohio State University. I also work closely with my clinical collaborators, spine surgeon Dr. Safdar Khan and veterinary neurosurgeon, Dr. Sarah Moore. There exists an unmet clinical need where the clinicians do not have access to the necessary tools and non-addictive biologics to treat low back pain and regenerate the IVD. My long-term research interests lie in understanding the Intervertebral disc (IVD) joint as a whole organ system and how the IVD and surrounding inflammatory and tissue microenvironment influence the pathogenesis of discogenic back pain while simultaneously developing novel non-viral reprogramming and immunomodulatory non-additive biological strategies for back pain. My training with Drs. Hoyland and Freemont, at Manchester, Dr. Kinloch at Pfizer, (Pain therapeutics) and with Bioengineer Dr. Iatridis has provided me with a strong background and research training in IVD pathophysiology and developmental biology, regenerative strategies for the IVD and ex vivo and in vivo animal models that has provided a solid platform to launch my academic career. In addition to research, my long-term teaching goals involve providing our biomedical engineering students with the necessary knowledge and transferable skill sets to help them identify and solve complex real world problems that exist at the intersection of Engineering and Medicine. In the research lab this is focused on independent thinking and problem solving as well as creativity associated with developing and testing unique hypotheses. In the classroom, this is focused on objectives and related outcomes to assess the students ability to synthesis knowledge, identify problems and solve real world problems through in-class activities, assignments and case studies. Furthermore, through my service I have supported a diverse and inclusive learning environment at the University and Scientific community level. This has included by roles in Louis Stokes Alliances for Minority Participation (LSAMP) program and Women in Engineering graduate council as well as providing professional development/educational and network opportunities at the National and International level through my roles as ORS Spine Section Membership Co-Chair and ORS New Investigator Committee member.
Kyle Kuchynsky - Ph.D Student
This is Kyle (that's me :D). I'm a 2019 alum of Ohio State, completing my Bachelor's in Biomedical Engineering. I was very interested in musculoskeletal biology in undergrad so I returned to complete a PhD, studying intervertebral disc biology. In particular, I'm interested in possible biological functions of cartilage endplate cells and factors that contribute to endplate degeneration and calcification. Outside of lab, I stay active by running; I also enjoy juggling, baking, and playing games on my Nintendo Switch.
Mary Heimann - Ph.D Student
Mary graduated from The Ohio State University with a B.S. in Biomedical Engineering and is currently pursing her PhD in the BME program. Her research focuses on therapeutics that target the immune response to mitigate degeneration in the IVD and neuropathic pain. This project seeks to establish the canine as a pre-clinical translational model for IVD degeneration and discogenic back pain. Outside of the lab, her hobbies include yoga, reading, baking, traveling, and snuggling up with her kitties.
Angelina Atieh
Angelina is a third-year Biomedical Science major, who is interested in exploring how cellular reprogramming using engineered extracellular vesicles can treat discogenic back pain. Previously, she worked in another Biomedical Engineering lab where she helped optimize a novel self-assembling peptide hydrogel using thiolene click chemistry reactions. Outside of research, she loves to try new foods, go to kickboxing classes, and travel. Post-graduation, Angelina hopes to attend medical school and continue working for Pelorus Health, a start-up company that focuses on pediatric diabetic disease management.
Isha Davit
Outreach and Involvement
