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Friday Evening Lecture Series
07/08/11
Lillie Auditorium, 8:00 PM
The Joe L. Martinez, Jr. and James G. Townsel Endowed Lectureship
"Bridging the Gap in the Fight Against Cancer: From the Operating Room to the Laboratory"
Alfredo Quiñones-Hinojosa, The Johns Hopkins University
Introduction by Joe L. Martinez
Lecture Abstract:
Glioblastoma (GBM) is the most common primary malignancy of the central nervous system (CNS) with a median survival of 14 months. These tumors represent a relentless disease state with a clear propensity towards migration and invasion. Because of their ability to extensively invade surrounding tissues, these tumors are refractory to combinatorial surgical resection, radiation, and chemotherapy. Increasing evidence suggests that small subsets of cells, referred to as brain tumor stem cells (BTSCs), retain tumor-initiating capacity and are responsible for the invasive and chemo/radioresistant nature of malignant gliomas. As a result, there is an impetus to find the mechanisms of migration as well as novel therapies targeting the BTSC population within GBMs. In our laboratory we have focused on mechanisms of stem cell migration as well as cell-based delivery of viral and non-viral (nanotechnology) treatments.
Regarding the mechanisms of migration, we have explored the role of the electroneutral Na+-K+-Cl- cotransporter 1 (NKCC1) in primary human glioma cells and its role in migration. Pharmacological inhibition and genetic inhibition of NKCC1 decreased glioma cell migration and invasion, in vitro and in vivo. NKCC1 modulated the migratory behavior of GBM cells by two different mechanisms: cell volume regulation (through ion transport) and regulation of focal adhesion dynamics and cell contractility. On the other hand, inhibition of K+-Cl- cotransporter (KCC), the counterpart of NKCC1 involving primarily a Cl- extruding mechanism, resulted in enhanced migratory behavior of GBM cells.
As we have begun to understand the mechanisms of migration of mesenchymal stem cells (MSC) towards brain tumors, we have engineered adipose-derived MSCs to secrete BMP4 in response to tumor-secreted TGF-β, representing a potential novel adjuvant therapy, which will preferentially target intracranial GBM utilizing relatively non-invasive routes of entry and therefore to be able to track the enhanced migratory BTSCs. Together, these innovations represent novel advances in both understanding cell migration and therapeutic and delivery modalities which may further our efforts to treat this devastating and incurable disease.
Dr. Alfredo Quiñones-Hinojosa is an Associate Professor of Neurosurgery and Oncology, Neuroscience and Cellular and Molecular Medicine at The Johns Hopkins University in Baltimore, Maryland. He serves as the director of the Brain Tumor Surgery Program at the Johns Hopkins Bayview Campus as well as the director of Neurosurgical Pituitary Center, Johns Hopkins University School of Medicine.
Dr. Quiñones focuses on the surgical treatment of primary and metastatic brain tumors, with an emphasis on motor and speech mapping during surgery. He is an expert in treating intradural spinal tumors as well as brainstem and eloquent brain tumors in adults with the use of neurophysiological monitoring during surgery. He has a strong interest in treating patients with skull base tumors and the use of radiosurgery as an adjunct to the treatment of these lesions.
Dr. Quiñones conducts numerous research efforts on elucidating the role of stem cells in the origin of brain tumors and the potential role stem cells can play in fighting brain cancer and regaining neurological function. In addition to leading the Brain Tumor Stem Cell Laboratory, he also heads the Neuro-Oncology Surgical Outcomes Research Laboratory where he is working to improve patient safety and maximize the efficacy of current treatment paradigms for patients with brain tumors.
Most recently, Dr. Quiñones was honored with a grant from the National Institutes of Health for his work with stem cells and cancer. His awards include a $450,000 Howard Hughes Medical Institute Physician-Scientist Early Career Award as well as being named one of the 100 most influential Hispanics in 2008. Dr. Quiñones was also awarded the Nickens Faculty Fellowship from the Association of American Medical Colleges, recognized for leadership in addressing inequities minorities face in medical education and health care.
Dr. Quiñones received a medical degree from Harvard University, where he graduated cum laude. He went on to complete his residency in neurosurgery at the University of California, San Francisco, where he also completed a postdoctoral fellowship in developmental and stem cell biology.
Joe L. Martinez, Jr., Ph.D. will introduce Dr. Quiñones. In 1994 Dr. Martinez received the American Association for the Advancement of Science Mentor Award for Lifetime Achievement. For 20 years he has directed the American Psychological Association Diversity Program in Neuroscience funded by National Institute of Mental Health (NIMH) to support the training of doctoral and postdoctoral students.
Dr. Martinez is the co-director (along with James Townsel) of the MBL Summer Program in Neuroscience, Ethics, and Survival (SPINES) course, supported by NIMH and designed to enhance the success of doctoral and postdoctoral students underrepresented in science. He served for 15 years as a full professor at the University of California, Berkeley. Currently he holds the Ewing Halsell Distinguished Chair at the University of Texas at San Antonio. His research is directed towards understanding how the brain stores memories. He investigates learning in animals, using behavioral, electrophysiological, and molecular techniques. He is currently conducting experiments using DNA gene chip technology looking for “memory genes.” He has over 175 publications. Students at all levels (postdoctoral, doctoral, masters and undergraduates) work in his laboratory to discover more about the brain’s workings. His book, Neurobiology of Learning and Memory, edited with Ray Kesner, is in its third edition and is popular with students. He is currently founder and Director of the Cajal Neuroscience Institute at the University of Texas San Antonio.
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