CINCINNATI—Andrew Grande, MD, a fellow in cerebrovascular/endovascular neurosurgery in the University of Cincinnati Department of Neurosurgery, has earned the 2010 William P. Van Wagenen Fellowship. The $120,000 fellowship, which funds a year of academic study abroad, is arguably the most prestigious in neurosurgery.
Grande will study with Professor Magdalena Götz at the Munich Institute of Stem Cell Research (Helmholtz Zentrum München). He will focus on neural (brain) stem cells, which were first discovered in the 1990s and which have the potential to divide and produce new cells, a process called neurogenesis.
The fellowship will enable Grande to investigate the ability of neural stem cells to replicate and communicate with other cells within the brains of animal models. The research could hold clues about how the brain tries to heal following an injury, such as stroke, and how stem cells that exist in the brain might be coaxed into creating a flood of healthy new cells for an injured area.
Specifically, Grande proposes to use retroviruses as a vehicle for inserting genes and transcription factors—special proteins that control the transfer of DNA—into various mouse models that have been engineered to express injury in different layers of brain tissue.
“I will work with Professor Götz and learn the technique,” Grande says. “I hope to demonstrate that not only are new neurons produced, and not only do they establish a connection with other cells, but that they are in fact talking to one another. And then I would hope to demonstrate that this communication leads to function, whether it is related to movement or vision.”
If scientists understand which transcription factors are important to the birth of new brain cells, or neurogenesis, they could potentially rev up the process by exposing the desired protein to a chemical. “Turning on the switch that overexpresses the transcription factor should result in the production of more neurons,” Grande says.
Grande envisions a day when physicians’ understanding of neural stem cells enables them to use endovascular techniques to treat injury caused by stroke by threading a tiny catheter up from the groin to the brain. “Some people think that endovascular surgery could be used to deliver stem cells to the brain,” Grande says. “That seems far-fetched, however. I think it is more likely that we will utilize existing stem cells; but perhaps what we can do is deliver various chemicals that will promote neurogenesis to specific areas of the brain.”
Grande is the third member of the Mayfield Clinic family to earn the Van Wagenen distinction. John Tew, MD, a Mayfield neurosurgeon who is clinical director of the UC Neuroscience Institute at University Hospital, was awarded the fellowship in 1969. Edmund Frank, MD, a graduate of the UC College of Medicine and UC’s residency program who is now a professor of neurosurgery at Oregon Health & Science University, was so honored in 1984.
Mario Zuccarello, MD, interim chairman of the department of neurosurgery and a neurosurgeon with the Mayfield Clinic, describes Grande as “a rare breed of clinical neurosurgeon” who is committed both to patient care and laboratory investigations. “He will be accomplished in both arenas,” Zuccarello says. “Dr. Grande has been a very active clinical investigator and has numerous publications in peer-review journals. Because he has a wealth of knowledge in both clinical and basic science areas, he has the potential to serve as a great model for his future residents and fellows, exemplifying the best qualities of both clinician and basic scientist.”
Grande, a native of St. Paul, Minn., received his medical degree from the University of Minnesota in 2003. He completed his neurosurgical residency at UC and the Mayfield Clinic in 2009 and is currently doing his fellowship in cerebrovascular/endovascular neurosurgery under the direction of Zuccarello; Andrew Ringer, MD, associate professor and director of endovascular neurosurgery; and Todd Abruzzo, MD, assistant professor of neuro-radiology.
Grande credits a long line of mentors with his success. While an undergraduate at St. Olaf College in Northfield, Minn., he conducted research in neuroscience in the laboratory of Esam El-Fakahany, PhD, professor in the departments of psychiatry, neuroscience and pharmacology at the University of Minnesota. As a medical student he worked with stroke models in the laboratory of Walter Low, PhD, at Minnesota’s Stem Cell Institute. And during his residency at UC he worked in the neurogenesis lab of Masato Nakafuku, MD, PhD, a professor in the division of developmental biology, at Cincinnati Children’s Hospital Medical Center. Grande also credits Tew.
In 2007 Grande earned two notable grants for his work in the regenerative potential of neural stem/progenitor cells in the adult neocortex: the AANS/CNS Section of Cerebrovascular Neurosurgery Research Grant and the Research Updates in Neuroscience for Neurosurgeons (RUNN) Research Award. Grande conducted his research under the direction of Nakafuku.
Grande also won UC’s 2009 Ellen and Stewart B. Dunsker, MD, Award for Clinical Research for demonstrating, in a cadaveric study, that shortening the vertebral column by 15 to 25 mm with a thoracolumbar osteotomy resulted in reduced tension in the spinal cord and nerve roots and could potentially be used to treat tethered cord syndrome. Grande conducted the research under the direction of Charles Kuntz IV, MD, associate professor and director of the division of spine and peripheral nerve surgery at UC. The approach to the rare spinal cord disorder was later used successfully by Kuntz and by neurosurgeons at Northwestern University.