M.D, Stanford University School of Medicine
PhD, Biophysics, Stanford University
BS, Biology and Biochemistry (Dual Major), Binghamton University
The central objective of my laboratory was to understand how extrachromosomal proteinaceous structural elements of the cell nucleus (hereafter-termed karyoskeletal elements) act to regulate nuclear structure and function. Three projects were pursued. 1) One project entailed the identification, biochemical characterization, and functional analysis of major karyoskeletal polypeptides. These include nuclear lamins and perhaps DNA topoisomerase II. Yeast (Saccharomyces cerevisiae) and fruit fly (Drosophila melanogaster) systems were used primarily and permit the genetic analyses essential for studying structural proteins for which in vitro activities are not yet defined. Results we obtained in Drosophila have been confirmed and/or extended with vertebrate cell types and tissues. This suggests that the Drosophila system is a suitable model for humans. 2) A second line of research dealt with the enzymology of eukaryotic DNA polymerases and their specific interactions with protein cofactors. A major focus concerned the polymerase cofactor, proliferating cell nuclear antigen (PCNA), and its role in human mutagenesis. Finally, we studied recognition, binding and repair of site-specifically damaged DNA. 3) A third project involved a human protein known to cause the neurodegenerative disease, spinocerebellar ataxia (SCA). Nuclear localization of the SCA protein is required for pathology, and pathogenesis presumably involves interaction(s) between the SCA protein and normal nuclear macromolecules.
I received both the MD and PhD degrees from Stanford University in California; the latter (Dr. David Korn, preceptor) was awarded “with distinction.” I chose to pursue a career in biomedical research, undertook a postdoctoral fellowship with Dr. Günter Blobel (recipient of the 1999 Nobel Prize in Physiology or Medicine) at the Rockefeller University in New York and have been a member of the Pharmacological Sciences Faculty at Stony Brook University since 1983. I am now Professor (since 1997) and Vice-Chair (since 2005).
My research career spanned more than three decades; through the years 1982-2005, I was continuously funded as a Principal Investigator (Project Director) by the US NIH. During this period, I also received funding sporadically from several other agencies including the American Cancer Society, the British Royal Society, RIKEN of Japan, the International Human Frontiers Science Program, NATO, the US-Israel Binational Science Foundation, and others.
I was also intimately involved in training highly-talented students in biomedical research. From 1988 to 2003, I served as Director of the Stony Brook MSTP (MD-PhD Program), submitted the first successful MSTP-training grant from this institution to the NIH-NIGMS (beginning in 1992 and ending in 1997), and renewed this NIGMS training grant for two successive five-year periods (1997-2002 and 2002-2007). Since 2003, I have served as Associate Director of this program.
With the termination of my competitive research funding in 2005, I decided, entirely for reasons of health, to end my research career (I no longer have a laboratory) and focus instead on medical education. I first became interested in medical education during my tenure as MSTP director, refined my interest through service from 1998-2003 on the NIH-NIGMS Study Section (BRT) involved in review of training grant applications, and since assuming the Vice-Chair position in our department, have been responsible for all aspects of our educational enterprise including a college undergraduate program, a program for nursing and allied health professions’ students, a PhD program in Pharmacology, and standard programs for both medical students and dental students. For the last six academic years, I have served as Course Director for Medical Pharmacology, a year-long course for second year students of both Medicine and Dentistry. I have also been heavily involved in curricular design and revision, both formally and informally, in both Medical and Dental Schools.
1. Fisher, P. A. 1987. Disassembly and Reassembly of Nuclei in Cell Free Systems (Minireview). Cell 48, 175‑176.
2. Fisher, P. A. 1994. Enzymologic Mechanism of Replicative DNA Polymerases in Higher Eukaryotes. In Progress in Nucleic Acid Research and Molecular Biology. W. Cohn and K. Moldave, eds. Vol. 47, Academic Press, NY, 371-397.
3. Fisher, P. A., and Berrios, M. 1998. Cell-Free Nuclear Assembly and Disassembly in Drosophila. In Methods in Cell Biology. M. Berrios, ed. Academic Press, NY, 397-416.
4. Pang, M., McConnell, M., and Fisher, P.A. 2005. The Drosophila mus308 Gene Product, Implicated in Tolerance of DNA Interstrand Crosslinks, is a Nuclear Protein Found in both Ovaries and Embryos. DNA Repair 4, 971-982.
5. Osouda, S., Nakamura, Y., de Saint Phalle, B., McConnell, M., Horigome, T., Sugiyama, S., Fisher, P.A., and Furukawa, K. 2005. Null mutants of Drosophila B-type lamin Dm0 show aberrant tissue differentiation rather than obvious nuclear shape distortion or specific defects during cell proliferation. Dev. Biol. 284, 219-232.
6. Furukawa, K., Ishida, K., Tsunoyama, T., Toda, S., Osoda, S., Horigome, T., Fisher, P.A., and Sugiyama, S. 2009. A-type and B-type lamins initiate layer assembly at distinct areas of the nuclear envelope in living cells. Exp. Cell Res. 315, 1181-1189.
Ph. D. (9 total)
M. Berrios (Rockefeller University) 1983
D. E. Smith 1988
B. M. Benton 1989
A. M. Whalen 1990
L. Lin 1991
L. Ng 1991
S. Weiss 1991
N. Maus 1994
M. Pang 2001
M. S. (3 total)
K. Doyle 1986
R. Cipriani 1992
A. Quamina 1999
Postdoctoral Fellows (17 total) Extramural Support
L.-C. C. Wu
D. E. Smith
S. Berrios WHO Fellowship
B. M. Benton DMDRP (NRSA)
V. H. Meller DMDRP (NRSA)
Individual NRSA (NIH)
K. Kawasaki NCI/JFCR Fellowship
N. Stuurman IHFSPO Fellowship
S. Bogachev Fogarty (NIH) Fellowship
D. Moutsiakis Supplement to ES04068
B. de Saint Phalle Individual NRSA (NIH)