18. GOALS FOR FELLOWSHIP TRAINING AND CAREER My career goal and primary interest is to become a practicing neurosurgical research scientist/surgeon and use bench science to lead to the advancement of neurosurgical techniques dealing with stroke and other neurological diseases. At the present time I have completed my first two years of medical school at Stanford University and am currently conducting work towards my PhD under Dr. Gary K. Steinberg M.D., Ph.D. Upon the completion of two years of clinical rotations, I will obtain my M.D. At that time, it is my intent to enter a neurosurgical residency and continue to the apply research and the knowledge that I have gained through this study. Ultimately, it is my goal to become a practicing physician and researcher. My specific interest in the physiological sciences developed during the many years of study in physiology, and neuroscience in turn, fostered the development of a profound curiosity in understanding the underlying mechanisms of disease. (Cont.) t_lol_No]i 19. NAME AND DEGREE(S) Gary K. Steinberg MD/Ph.D 20. POSITION/RANK Professor and Chairman 21. RESEARCH INTERESTS/AREAS Elucidating the pathophysiology of cerebral ischemia and in developing neuroprotective strategies to improve outcome after stroke. .-,_-t __._1,_-m-ail,lipl.-fl i22. 0EaCRIPTION (Do no).exceeq.sp.aqe provident),, , posit that the mlgrtanon, alVlSlOn, ana iate of neural stem cells in the adult SVZ is altered following ischemic injury. First I will characterize the normal biology of the adult SVZ, migration patterns, cell fate, and clonality of migrating cells using retroviral marking in vivo. This will be accomplished by two BrdU staining paradigms. One will identify the phenotype and location of S-phase cells at 1, 3, 7, 14 and 28 days by pulsing single BrdU injections at the time point of interest followed by sacrifice two hours later. The second paradigm involves BrdU injections for six consecutive days followed by sacrifice at 7, 14, and 28 days after the initial BrdU injection to determine cell fate and phenotype of dividing cells that accumulate over the course of one week. Unbiased stereology and confocal microscopy will provide data on absolute numbers and locations of each cell. Finally, it has been observed that increasing neuronal number (i.e. transplant) following stroke improves behavioral outcome. This section of the project attempts to determine if amplifying or suppressing stem cell activity and/or neurogenesis in response to injury changes functional outcome. This question will be addressed by influencing stem cell fate through expressing proneuronal or proglial (i.e., neurogenic) proteins such as noggin or neuroD 1 or bmp4 and jagged-1 respectively. Dr. Tim Schallert has developed sensitive and detailed methods of behavioral assessment focused on limb asymmetry These methods will be used to assess if enhancing glial or neuronal fate influences behavioral outcome. PHS 416-1 (Rev. 12/98) Form Page 2 BB Individual NRSA Application NAME OF APPLICANT (Last, first, middle initial) Continuation Page Hoehn, Benjamin, D (18 Cont.) Almost all of my education over the past ten years has been spent in pursuing this interest. In order to accomplish my goal it was obligatory that I develop a comprehensive knowledge of how molecular and physiological research can be applied to medical practice, as well as the learning techniques and skills of inquiry. This would allow a deeper understanding of the relationship of theory and practice. I believe that this award would make it financially possible for me to complete my current training goals, as well as advance knowledge surrounding the involvement of endogenous stem cells in the evolution of strokes. It is my hope that this knowledge will aid in the development of treatments for a disease that is the number one debilitating, and the third leading killer of Americans. O Z I-- fii , [l. Z O m I-. , Z m I-- Z O O PHS 416-1 (Rev. 12/98) Page 3 cc NAME (Last, first, middle initial) Individual NRSA Application Table of Contents ========================================Section End===========================================

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30NS045494-03
Application #
6839942
Study Section
NST-2 Subcommittee (NST)
Program Officer
Owens, David F
Project Start
2003-01-01
Project End
2007-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
3
Fiscal Year
2005
Total Cost
$39,042
Indirect Cost
Name
Stanford University
Department
Biology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Hoehn, Benjamin D; Palmer, Theo D; Steinberg, Gary K (2005) Neurogenesis in rats after focal cerebral ischemia is enhanced by indomethacin. Stroke 36:2718-24