Congratulations Michael Orr, PhD
On Wednesday, March 24, 2021 Michael Orr successfully defended his dissertation and earned his doctoral degree. Congratulations, Dr. Orr!
"UNDERSTANDING ENDOGENOUS SPINAL REPAIR THROUGH A NOVEL MAMMALIAN MODEL OF SPINAL CORD INJURY"
Doctoral Committee Members
Dr. John Gensel, Department of Physiology, Mentor
Dr. Kathy Saatman, Department of Physiology
Dr. Steven Estus, Department of Physiology
Dr. Warren Aliliain, Department of Neuroscience
Dr. Ashley Seifert, Department of Biology
Outside Examiner: Dr. Ann Morris, Department of Biology
Abstract of Dissertation
Spinal cord injury (SCI) is devastating and often leaves the injured individual with persistent dysfunction. The injury persists because humans have poor wound repair and there are no pharmacologic treatments to induce wound repair after SCI. The continued efforts to discover therapeutic targets and develop treatments heavily rely on animal models. Lab mice (Mus musculus) are a powerful tool for recapitulating the progression and persistent damage evident in human SCI, but they do not provide insight to naturally occurring wound repair. Some non-mammalian species and neonates, on the other hand, can be used to identify therapeutic targets because they naturally regenerate spinal tissues. Unfortunately, translating therapeutic targets from non-mammalian or neonatal models to humans is onerous due to their phylogenetic and developmental disparity from adult mammals. This project investigates SCI in the African spiny mouse (Acomys cahirinus), a rodent species with robust wound repair. In this investigation, I have identified enhanced functional recovery and tissue integrity in Acomys compared to Mus. Further investigations show that Acomys respond to injury with a dampened inflammatory and fibrotic scarring response, including a decrease in cells with fibroblast markers. The association of dampened inflammatory and fibrotic scarring responses with enhanced tissue integrity and functional recovery in the subacute window after SCI suggests that inhibiting subacute inflammatory and fibroblast proliferation and activation may be an effective strategy for inducing endogenous functional repair in the mammalian spinal cord. Further studies of SCI in Acomys can continue to illuminate the mechanism of endogenous repair in the mammalian spinal cord. Collectively, my graduate studies have identified novel therapeutic targets and optimal contexts that may be developed to induce endogenous spinal repair in mammals.
Acknowledgements
All that I have done and all that I am is the product of an incredibly blessed life filled with many loved ones. Mom and Dad, thank you for always prioritizing me and my education. You have been a constant source of support, encouragement, and love as I continue to learn and grow. Andrew and Stephen, thank you for being my best friends and confidants through all of life’s seasons, especially when I need a diversion. Randolphs, thank you taking me in as one of your own and showing me all the love a son could ask for. Molly Ann, you deserve thanks for every word I have written and all the life that has been lived in their making.
My PhD would not be possible without the incredible advisors and co-workers with whom I have had the privilege to work. Dr. Gensel, you have a profound positive impact on my life, especially during this time of personal growth and development. I am continually reminded of how lucky I am to be working with you. Thank you to my many other mentors—especially those on my committee, in Physiology, and in SCoBIRC—who helped shape me as a professional and a scientist. Thank you to all my co-workers—especially Will, Tim, Andrew, Binoy, Zel, Steve, Bei, Jennifer, Chris, Sabryn, Kristin, and Corin—for your patience and tolerance, and for the incredible amount of work you have done to complete this project. My world is better for you all, and I hope you are proud of the fruits of all your hard work.Finally, thank you to all my wonderful friends—especially Sarah, Shelby, Zach, Anthony, Chelsea, and Mitch—for lending an ear and inspiration on many occasions, and for helping me stay sane and smiling all along the way.
