John Fike PhD
Professor of Neurological Surgery, Radiation Oncology, and Radiology
Principal Investigator, Brain and Spinal Injury Center
In the management of malignant brain tumors, radiation therapy is the single most effective treatment after surgical resection, but the radiation dose that can be used is limited by the tolerance of normal brain tissue. Radiation injury is manifold in character, ranging from mild morphologic changes and cognitive deficits to gross tissue destruction leading to severe disability. To understand the cellular/molecular sequence of events in the pathogenesis of radiation injury, and in order to be able to modify its development or extent, it is critical to identify the cell population(s) involved and to determine if those populations can be manipulated to affect a recovery or repair of radiation damage. Dr. Fike's laboratory is involved in studies on the cellular basis of radiation injury, using both in vitro and in vivo models.
In the forebrain of adult mammals, including man, there are 2 major sites of proliferative activity: the subependyma (SE) and the subgranular zone (SGZ) of the dentate gyrus. Neural stem/precursor cells are present in these areas and produce cells that migrate and differentiate into 3 major cell components of normal brain: neurons, astrocytes, and oligodendrocytes. Dr. Fike contends that the cells of the SE and the SGZ play important roles in the reaction of normal brain after irradiation, and that the response of such cells can be modified, thereby decreasing the extent or severity of damage. Dr. Fike's studies of the cellular and, ultimately, the molecular mechanisms associated with tissue responses within the brain, will not only increase knowledge of the neurobiology of the SE and SGZ, but it is hoped, will lead to a better understanding of radiation injury and to new strategies to combat this clinically significant problem.
Education, Training, and Previous Positions
- 1970: BA, California State University, Long Beach
1972: MS, University of California, Irvine
1978: PhD, Colorado State University, Fort Collins
1978-1979: NIH Post Doctoral Fellow, Department of Radiation Oncology, The George Washington University Medical Center, Washington, DC
1979-1980: NIH Post Doctoral Fellow, Department of Radiation Oncology, UCSF
1980-1981: Assistant Research Radiobiologist, Department of Radiation Oncology, UCSF
1981-1983: Assistant Professor, Departments of Radiation Oncology and Radiology, UCSF
1983-1991: Assistant Professor, Departments of Neurological Surgery, Radiation Oncology and Radiology, UCSF
1991-1998: Associate Professor, Departments of Neurological Surgery, Radiation Oncology and Radiology, UCSF
Selected Professional Memberships and Appointments
- Radiation Research Society
American Society for Therapeutic Radiology and Oncology
American Association for the Advancement of Science
Society for Neuroscience
Society for Neuro-Oncology
National Neurotrauma Society
Selected Honors and Awards
- 1981-1984: NIH Young Investigator Research Award
1982: Alberta Heritage Foundation for Medical Research Visiting Lecturer. Cross Cancer Institute, Edmonton, Alberta, Canada
1987: Travel Award to attend International Radiation Research Society Meeting in Edinburgh, Scotland
1995: Travel Award to attend International Radiation Research Society Meeting in Wurzburg, Germany
1999: Travel Award to attend International Radiation Research Society Meeting in Dublin, Ireland
2003: Henry Ford Neurosurgery Distinguished Researcher Lecture. Henry Ford Hospital, Detroit Michigan
2008: Chairperson, Radiotherapy and Biology Study Section, National Institutes of Health
Selected Recent Publications
Acharya MM, Christie LA, Lan ML, Donovan PJ, Cotman CW, Fike JR, Limoli CL. Rescue of radiation-induced cognitive impairment through cranial transplantation of human embryonic stem cells. Proc Natl Acad Sci U S A 2009;106(45):19150-19155.
Andres-Mach M, Rola R, Fike JR. Radiation effects on neural precursor cells in the dentate gyrus. Cell Tissue Res 2008;331(1):251-62.
Rola R, Zou Y, Huang TT, Fishman K, Baure J, Rosi S, Milliken H, Limoli CL, Fike JR. Lack of extracellular superoxide dismutase (EC-SOD) in the microenvironment impacts radiation-induced changes in neurogenesis. Free Radic Biol Med 2007;42(8):1131-45.
Fike JR, Rola R, Limoli CL. Radiation response of neural precursor cells [Review]. Neurosurg Clin N Am 2007;18(1):115-27, x.
Fan Y, Liu Z, Weinstein PR, Fike JR, Liu J. Environmental enrichment enhances neurogenesis and improves functional outcome after cranial irradiation. Eur J Neurosci 2007;25(1):38-46.
Limoli CL, Giedzinski E, Baure J, Doctrow SR, Rola R, Fike JR. Using superoxide dismutase/catalase mimetics to manipulate the redox environment of neural precursor cells. Radiat Prot Dosimetry 2006;122(1-4):228-36.
Limoli CL, Giedzinski E, Baure J, Rola R, Fike JR. Redox changes induced in hippocampal precursor cells by heavy ion irradiation. Radiat Environ Biophys. 2007;46(2):167-72.
Limoli CL, Giedzinski E, Baure J, Rola R, Fike JR. Altered growth and radiosensitivity in neural precursor cells subjected to oxidative stress. Int J Radiat Biol 2006;82(9):640-7.
Pullela R, Raber J, Pfankuch T, Ferriero DM, Claus CP, Koh SE, Yamauchi T, Rola R, Fike JR, Noble-Haeusslein LJ. Traumatic injury to the immature brain results in progressive neuronal loss, hyperactivity and delayed cognitive impairments. Dev Neurosci 2006;28(4-5):396-409.
Rola R, Mizumatsu S, Otsuka S, Morhardt DR, Noble-Haeusslein LJ, Fishman K, Potts MB, Fike JR. Alterations in hippocampal neurogenesis following traumatic brain injury in mice. Exp Neurol 2006;202(1):189-99.
Otsuka S, Coderre JA, Micca PL, Morris GM, Hopewell JW, Rola R, Fike JR. Depletion of neural precursor cells after local brain irradiation is due to radiation dose to the parenchyma, not the vasculature. Radiat Res 2006;165(5):582-91.
Vit JP, Ohara PT, Tien DA, Fike JR, Eikmeier L, Beitz A, Wilcox GL, Jasmin L. The analgesic effect of low dose focal irradiation in a mouse model of bone cancer is associated with spinal changes in neuro-mediators of nociception. Pain 2006;120(1-2):188-201.
Rola R, Sarkissian V, Obenaus A, Nelson GA, Otsuka S, Limoli CL, Fike JR. High-LET radiation induces inflammation and persistent changes in markers of hippocampal neurogenesis. Radiat Res 2005;164(4 Pt 2):556-60.
Giedzinski E, Rola R, Fike JR, Limoli CL. Efficient production of reactive oxygen species in neural precursor cells after exposure to 250 MeV protons. Radiat Res 2005;164(4 Pt 2):540-4.