The Pepper Lab explores the key mechanisms that drive nerve regeneration after injury. Our goal is to identify new cellular and small molecule-based strategies that improve the clinical treatment of nerve injury. Our lab is the scientific arm of the Stanford Facial Nerve Center, a specialized, multidisciplinary treatment center for facial paralysis and related conditions.
Regeneration of nerve tissue and blood supply after nerve injury
Nerve injury, whether the result of trauma or surgical transection in preparation for repair, has long been viewed differently than other soft tissue wounds. However, like all wounds, nerve injury requires a regenerative response that restores the structure and blood supply of the injured tissue.
Using a microsurgical model of facial nerve injury in the mouse that we developed, our research explores the molecular pathways that drive nerve tissue regeneration after injury. We are particularly intrigued by the ways that nerve connective tissue, or mesenchyme, responds to injury. Our prior work has highlighted the role of the Hedgehog pathway in mediating this response to nerve injury.
This image, featured on the cover of Experimental Neurology, shows endoneurial fibroblasts (marked in red) repopulating the injured facial nerve. Our subsequent work has shown that these endoneurial fibroblasts participate in repair of the injured nerve and likely express angiogenic factors that help to restore the blood supply of the nerve.
Improving Nerve Regeneration After Injury
Based on our prior work, we now employ targeted small molecules to modulate key signaling pathways as a means of increasing the rate of recovery after facial nerve transection injury.
Small molecules applied during the time of nerve injury and recovery may hasten the recovery of the nerve. The top image shows a facial nerve two weeks after transection injury, with the mouse treated with a small molecule before and after nerve injury. A mouse treated with vehicle is shown below, also two weeks after facial nerve transection injury
Surgical Innovation at the Stanford Facial Nerve Center
Our scientific discoveries in the lab improve the ways in which we treat our patients. Our work on facial nerve regeneration in the mouse model has informed the development of new microsurgical techniques for the treatment of facial paralysis.
The Dual Nerve Transfer for facial reanimation describes the combination of a masseteric nerve transfer with a simultaneous end-to-side nerve transfer of the proximal facial nerve to the hypoglossal nerve.
Jon-Paul Pepper, MD
Dr. Pepper is the Director of the Stanford Facial Paralysis Center and directs both the scientific and clinical work that is dedicated to improving outcomes after facial nerve injury. He has directed a research lab focused on nerve regeneration since 2013 and moved both his clinical practice and research to Stanford University in 2017. While on faculty at the University of Southern California he was awarded the Research Mentor Award in 2016-17.
Meet Our Team
Lili He, PhD
Lili is a Life Science Research Professional who completed her PhD in Pathology and Cell Biology at the University of South Florida in 2008. She joined the Pepper Lab in 2019 and is working on vascular imaging of peripheral nerves and the role of endoneurial fibroblasts in nerve graft survival.
Natalia Castillo Ramos, Undergraduate Student
Natalia is an undergraduate student studying bioengineering and psychology at Stanford. She is interested in the morphological changes taking place in the nerve throughout the recovery process and how it relates to functional recovery of movement. She also has research interests in clinical neuroscience and behavior outcomes of injury and trauma. In her free time, she enjoys reading, dancing and spending time with her family and friends.
Zachary Kim, Undergraduate Student
Zachary is an undergraduate student at Stanford University, majoring in Biology. He joined the Pepper Lab in 2021. Zachary grew up in New Jersey and likes to golf and do archery in his free time.
Praveen Sundar, Undergraduate Student
Praveen is an undergraduate sophomore studying Biomechanical Engineering. Praveen’s interest and his current project in the lab lie in prostheses and nerve regrowth. Within the lab, my current project deals with Fibrinogen and Thrombin combinations, as well as 3D bio-printing scaffolding made specifically for nerve repair.
Justine Sato, Undergraduate Student
Justine Sato is an undergraduate student at Stanford University studying biomechanical engineering. In the Pepper Lab, she is collaborating on a project focused on localized drug delivery to the site of injury during nerve surgery. In her free time, she likes playing trumpet with several of Stanford’s musical organizations and studying Japanese.
Lab Alumni (mentees)
Chrisa Faniku, PhD
Dr. Faniku completed her PhD in Biomedical Sciences at Glasgow Caledonian University in Scotland. She was a postdoctoral fellow in Dr. Pepper’s lab from 2018 to 2022. Her manuscript, “Hedgehog signaling promotes endoneurial fibroblast migration and Vegf-A expression following facial nerve injury” was published in Brain research in 2021. Her research on this topic was awarded a 1st place prize at the Stanford Bio-X Symposium in 2020 and was presented at the Society for Neuroscience in 2019.
Max Bjorni, BS
Max majored in Neuroscience at Santa Clara University and completed a visiting student rotation in the Pepper Lab in 2019-2020.
Tiffany Wang, MD
Tiffany completed a co-first author publication that described the use of human induced pluripotent stem cells for the derivation of motor neurons. Using a mouse model of sciatic nerve injury, she successfully transplanted and engrafted these cells into immunodeficient mice. Her work was published in a JAMA-series publication. She matched at a highly competitive and sought after residency position in Otolaryngology at Harvard University, the Massachusetts Eye and Ear Infirmary, where she is completing her clinical training.
Gabriela Bobarnac, MD
Gabby focused her work as Dean’s scholar on the injury-responsive mesenchyme in the mouse facial nerve. She described a population of endoneurial fibroblasts in the facial nerve that proliferate after injury and replenish the injury site and the perineurium of the injured nerve. Her work was accepted for publication by Experimental Neurology and was featured on the cover of Volume 303 in 2018. She matched into a highly competitive residency position in Otolaryngology at the Oregon Health and Sciences University.
Ways to Get Involved
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As a translational research group, we are excited to collaborate with energetic scientists and clinician-scientists who share our passion for our mission. A limited number of research fellowship positions are offered in the lab throughout the year. Minimum length of the fellowship program is 12 months; shorter periods of time might be considered under special circumstances. Please contact us if you are interested in joining our group!
Chrisa Faniku wins the Stanford Bio-X best poster award
On February 26th, our postdoc, Chrisa Faniku, presented her poster “The Role of Hedgehog Signaling in Facial Nerve Regeneration Following Injury” at the Stanford Bio-X Interdisciplinary Initiatives Seed Grants Program Poster Session.
Bio-X program would like to congratulate her on the excellence and presentation of the poster. Of the 100 posters presented, it was selected as a winner!