(6aj) Interstitial Fluid Flow and Transport in Neural Trauma and Disease

Nearly 100 million Americans suffer from at least one of over 1,000 described neurological diseases. Many of these diseases are associated with alterations in cerebral blood flow, the blood-brain barrier, the extracellular matrix, and/or drainage pathways such as the meningeal lymphatics. Hence, regulators of fluid flow within neural tissue are emerging as an underlying connection between seemingly disparate neuropathologies. While bulk flow around the brain is well studied, researchers are only starting to characterize the effects of fluid transport within the interstitial space between neural cells, coined interstitial fluid flow. The magnitudes of interstitial fluid flow and the resulting shear forces are typically low in the brain under normal physiological conditions, so even small perturbations can affect neural cell function. One prime example is in glioblastoma, the most common and deadly brain tumor. My postdoctoral research has focused on studying effects of interstitial fluid flow and shear stress on tumor-adjacent neural cells called the tumor microenvironment. We have shown that interstitial fluid flow significantly increases at tumor-brain interfaces, and these convective forces stimulate neural cells to enhance cancer cell invasion. We can effectively reduce glioma cell dissemination by preventing this flow stimulation, thereby demonstrating the therapeutic potential of altering responses to flow in the brain.

In my own research program, I will combine my expertise in interstitial fluid flow with my training in neural tissue engineering and biomaterial development towards creating novel strategies for neural regeneration. My initial approach will be to 1) characterize interstitial fluid dynamics and the contributions to neurodegeneration after spinal cord injury, 2) engineer hydrogel systems for controlling interstitial flow in vitro and in vivo, and 3) develop polymer-based strategies for modulating neural cell phenotype after injury and in disease. My overarching goal is to understand fluid flow dynamics in the nervous system and the resulting impacts on the neural cell microenvironment such that we can engineer better therapies for these debilitating disorders.

Teaching Interests:

My passion for teaching started in high school when I first tutored a friend three grades my senior in her Advanced Algebra class. This experience motivated me to develop my one-on-one teaching skills in college by tutoring student athletes, and I eventually became a primary tutor of the center’s “Math Lab.” In graduate school, I led small groups as a teaching assistant for the Fundamentals of Chemical Engineering lab course at the University of Texas and gave a guest lecturer for the University of Florida’s Student Science Training Program. As a postdoctoral researcher, I co-instructed the Integrative Design and Experimental Analysis lab course at the University of Virginia where I both delivered lectures and directed lab classes focused on mass transport in tissue engineering. I am currently helping develop an international cancer course titled "Frontiers in Cancer Engineering" in which my postdoctoral advisor and I will introduce a small class of graduate students at Virginia Tech to cancer research in Europe through telecommunicated lectures and site visits to research laboratories across Switzerland. I want to continue to develop my skills as an educator and look forward to the challenge of continually tailoring lectures to the needs of the class, both in established courses and courses I develop.

Teaching Philosophy

My goal as an educator is to share with students my fascination of the physical world and the human body, highlighting methods that scientists and engineers are leveraging to treat real-world problems. I will focus my teaching philosophy on three main objectives: 1) provide resources to enable students to enhance their educational experience as needed to fit their learning needs, 2) demonstrate connections across the range of course topics to promote an integrative understanding, and 3) provide context to the real world by incorporating examples based on cutting-edge research. I am most interested and qualified to teach introductions to mass and energy balances and transport phenomena. For more advanced courses, my interests and research expertise make well suited to teach courses on mass separations, polymeric biomaterials, and engineering physiology. I am also particularly interested in developing an advanced course on neuro-immune engineering.

Mentorship

I have been fortunate enough to work in both a well-established, medium-sized program (12+ trainees) and a newer, smaller program (3-6 trainees). These experiences have taught me that my mentor style will need to adapt to both the requirements of individual mentees as they progress throughout their training as well as my career stage. Nonetheless, my guiding principle for mentoring students will always be to cultivate their intellectual independence while highlighting the importance of collaboration. I will use group and individual meetings to develop my mentees’ abilities to design and implement impactful, innovative research projects, critically examine the literature and reflect on their own methods and goals, effectively communicate research results to the scientific and general communities, and hone their professional development skills for realizing their career objectives.

Education:

Ph.D., University of Texas at Austin, Chemical Engineering, 2015

B.S., University of Tennessee at Knoxville, Chemical and Biomolecular Engineering, 2011

Postdoctoral Project: “Defining and targeting the effects of interstitial fluid flow on the brain tumor microenvironment” under supervision of Jennifer M. Munson, originally at University of Virginia and currently at Virginia Polytechnic Institute and State University.

Ph.D. Dissertation: “An injectable acellular nerve graft as a platform for treating spinal cord injury” under supervision of Christine E. Schmidt, originally at University of Texas and currently at the University of Florida.

Selected Peer-Reviewed Publications:

1. Cornelison RC, Brennan CE, Munson JM. “Convective forces increase CXCR4-dependent glioblastoma cell invasion in GL261 murine model.” (under revision at Scientific Reports)
2. Cornelison RC, Wellman SW, Park JH, Porvasnik SL, Song YH, Wachs RA, Schmidt CE. “Development of an apoptosis-assisted decellularization method for maximal preservation of nerve tissue structure.” (under review at Acta Biomaterialia)
3. Da Mesquita S, Louveau A, Vaccari A, Smirnov I, Cornelison RC, Kingsmore KM, Contarino C, Onengut-Gumuscu S, Farber E, Raper D, Viar KE, Baker W, Dabhi N, Oliver G, Rich S, Munson JM, Overall CC, Acton ST, Kipnis J. “Functional aspects of meningeal lymphatics in aging and Alzheimer’s diseas” Nature, (in press).
4. Cornelison RC and Munson JM. “Perspective on translating biomaterials into glioma therapy: Lessons from in vitro models.” Frontiers in Materials, 5 (2018): 27.
5. Cornelison RC, Gonzalez-Rothi EJ, Porvasnik SL, Wellman SM, Park JH, Fuller DD, Schmidt CE. “Injectable hydrogels of optimized acellular nerve for injection into the injured spinal cord.” Biomedical Materials, 13.3 (2018): 034110.

Patents:

Schmidt CE, Wachs RA, Cornelison RC. “Tissue Decellularization Methods” (2017). International Publication No.: WO/2017/011653.