Medical Development
Resume:
KAZUKI HAGIHARA
Permanent resident in the US
***** ****** **. *** *****, CA 92126
Tel.: 858-***-****
E-mail: abm30q@r.postjobfree.com
SUMMARY
A senior research scientist specializing in neurobiology with broad
background in biochemistry, molecular biology, cell biology, glycobiology,
genetics, mouse surgery, and behavior analysis. Comprehensive understanding
of basic and clinical medicine, with experiences in training and
collaborating with scientists and clinicians.
RESEARCH EXPERIENCE
Research Scientist
Cell Applications, Inc., San Diego, CA (2009-present)
. Evaluating antibodies and compounds using immunobloting and
flowcytometry
. Developing transfection kits and cell migration kits
Research Associate, Molecular and Integrative Neurosciences Department
(MIND)
The Scripps Research Institute, San Diego, CA (2006-2009)
. Analyzed metabolic molecules in primary astrocyte cultures after
cocaine, glutamate, alcohol stimulation using enzyme assays and HPLC.
. Performed surgeries of IV catheters, ICV, and IC in mice and analysis
of cocaine self- administration in mice using genetic and
pharmacological methods. Trained one posdoc in stereotaxic surgeries.
Postdoctoral Associate, Dept. of Neurobiology & Signal Transduction
Burnham Institute, La Jolla, CA (1998-2006)
. Analyzed the role of a tyrosine phosphatase and the related molecules
in brain specific knockout mice. Trained one graduate student
and one postdoc in neuroscience techniques.
. Determined the structure of PSD like protein, Synbindin gene using
sequencing, PCR, 5' race and EST, and constructed the targeting
vectors for the conditional knockout mice. Demonstrated the
distribution of Synbindin in brain by affinity-purified antibodies and
in situ hybridization and the detail localization in synapses using
immunoelectron microscopy.
. Proved the limited expression of heparan sulfate proteoglycan,
Glypican-4 in neural precursor cells and the relation with FGF2 using
a variety of scientific techniques and approaches. Collaborated with
one scientist (Glypican-4 is an endostatin receptor) and three
scientists (stereotaxic brain surgery, spinal cord surgery, in situ
hybridization). Made stable transfectants (Jurkat cells) expressing
Glypican-4 screening by flow cytometry and demonstrated that heparan
sulfates effect cell aggregation using aggregation assay. Collected
experimental data and contributed to get a successful application of
NIH grant (Glypican-4).
. Indicated that ES cells have hyaluronans, chondroitin sulfate
proteoglycans, and heparan sulfate proteoglycans using gel filtration
after metabolic labeling of them. Collected experimental data and
contributed to get a new NIH grant (Hyaluronan synthesizing enzyme-2)
and renew a NIH grant.
. Trained two postdoctoral fellows to use in situ hybridization
technique and one Laboratory Assistant to conduct genomic PCR of
transgenic mice.
. Indicated the Brevican-Tenascin-R interaction by immunohistochemistry
using serial sections and confocal microscope and the expression of
Brevican in perineural nets by immunohistochemistry and immunoelectron
microscopy. Showed that Brevican exists in the protoplasmic inlet in
the internal granular layer of cerebellum and is synthesized by
astrocytes using immunohistochemistry and in situ hybridization.
Postdoctoral Fellow Dept. of Neurobiology & Behavior
Rockefeller University, New York, NY (1992-1998)
. Cloned mouse Progesterone gene and demonstrated that DNase
hypersensitivity sites in 5'upstream of Progesterone receptor gene are
tissue-specific (liver, hypothalamus, uterus).
. Injected antisense oligonucleotides of Progesterone receptors in mouse
hypothalamus using stereotaxic brain surgery in order to suppress the
expression of the mRNAs, and assayed the level of progesterone
receptors using steroid receptor binding assay and
immunohistochemistry.
. Trained one postdoc to use Northern blotting and one postdoc to run
DNase hypersensitivity assay.
Clinical Research Associate, Dept. of Obstetrics & Gynecology, Yamanashi
Medical School, Tamaho, Yamanashi, Japan (1991-1992)
. Demonstrated the distribution of progesterone receptor mRNA in rat
brain using in situ hybridization.
. Presented the expression of progesterone receptor in the neonatal rat
cerebral cortex using RT-PCR.
. Trained one M.D. to run in situ hybridization experiments. Trained
medical students and one recently graduated M.D. in Obstetrics &
Gynecology.
RESEARCH TECHNIQUES
Animals (mouse & rat): tissue dissection; stereotaxic brain surgery
(including intraventicular canules); jugular vein catheter surgery;
behavioral analysis (cocaine self-administration); cardiac perfusion; blood
sampling from ophthalmic vessels.
Cell Biology: transfection (transient & stable); neural cell culture;
neural stem cell culture; hippocampal slice culture; immunocytochemistry;
collagen gel explant migration assay; mitogenesis assay; metabolic
labeling.
Molecular Biology: DNA, RNA extraction; plasmid construction; mutagenesis;
Northern, Southern blotting; DNase hypersensitivity assay; genomic cloning;
RT-PCR; real time PCR; 5'-race; sequencing.
Biochemistry: ELISA; HPLC; protein expression & purification;
immunoblotting; immunoprecipitation.
Histology: cryostat sectioning; paraffin sectioning; immunohistochemistry;
in situ hybridization; immunoelectron microcopy; confocal microscopy.
EDUCATION
Ph.D. Biochemistry, Graduate school of Yamanashi Medical School (Japan)
1991
M.D. Yamanashi Medical School (Japan) 1987
AFFILIATIONS
Society for Neuroscience
PUBLICATIONS
1. Repunte-Canonigo V, Francesconi W, van der Stap LD, Lourdusamy A, Wagner
U, Sabino V, Cottone P, Jarvelin MR, Elliott P, Isohanni M, Hagihara K,
Reifel-Miller A, Zorrilla EP, Berton F, Roberts AJ, Morales M, Schumann
G, and Sanna PP: Genome-wide gene expression analysis identifies K-ras as
a regulator of alcohol intake. PNAS. Submitted.
2. Hagihara K*, Zhang EE*, Ke Y*, Liu G, Liu J-J, Rao Y, Feng GS: Shp2 acts
as a critical downstream signal of SDF-1/CXCR4 in granule cell migration
during cerebellar development. Developmental biology. Accepted.
3. Francesconi W, Berton F, Repuente-Canonigo V, Hagihara K, Thurbon D,
Lekic D, Specio S, Greenwell T, Chen S, Rice K, Richardson H, O'Dell L,
Zorrilla E, Morales M, Koob G, and Sanna PP: Protracted withdrawal from
alcohol and drugs of abuse impairs long-term Potentiation of intrinsic
excitability in the juxtacapsular bed nucleus of the stria terminalis. J
Neurosci. 29:5389-5401, 2009.
4. Ke Y*, Zhang EE*, Hagihara K*, Wu D, Pang Y, Klein R, Curran T, Ranscht
B, Feng GS: Deletion of Shp2 in the brain leads to defective
proliferation and differentiation in neural stem cells and early
postnatal lethality. Mol Cell Biol. 27:6706-17, 2007.
5. Suzuki M, Suzuki M, Nakayama J, Suzuki A, Angata K, Chen S, Sakai K,
Hagihara K, Yamaguchi Y, Fukuda M: Polysialic acid facilitates tumor
invasion by glioma cells. Glycobiology 15:887-894, 2005.
6. Zhang EE, Chapeau EA, Hagihara K, Feng GS: Neuronal Shp2 tyrosine
phosphatase controls energy balance and metabolism. PNAS 101:160**-*****,
2004.
7. Karumanchi SA, Jha V, Ramchandran R, Karihaloo A, Tsiokas L, Chan B,
Dhanabal M, Hanai J, Venkataraman G, Shriver Z, Keiser N, Kalluri R,
Zenge H, Mukhopadhyay D, Chen RL, Lander AD, Hagihara K, Yamaguchi Y,
Sasisekharan R, Cantley L, Sukhatme V: Cell surface glypicans are low-
affinity endostatin receptors. Molecular Cell 7:811-822, 2001
8. Ogawa T, Hagihara K, Suzuki M, Yamaguchi Y: Brevican in the developing
hippocampal fimbria: differential expression in myelinating
oligodendrocytes and adult astrocytes suggests a dual role for brevican
in CNS fiber tract development. J Comp Neurol 432:285-295, 2001
9. Ethell IM, Hagihara K, Miura Y, Irie F, Yamaguchi Y: Synbindin, a novel
syndecan-2-binding protein in neuronal dendritic spines. J Cell Biol
151:53-68, 2000
10. Hagihara K, Watanabe K, Chun J, Yamaguchi Y: Glypican-4 is an FGF2-
binding heparan sulfate proteoglycan expressed in neural precursor cells.
Dev Dyn 219:353-367, 2000
11. Hagihara K, Miura R, Kosaki R, Berglund E, Ranscht B, Yamaguchi Y:
Immunohistochemical evidence for the brevican-tenascin-R interaction:
colocalization in perineuronal nets suggests a physiological role for the
interaction in the adult rat barin. J Comp Neurol 410:256-264, 1999
12. Miura R, Aspberg A, Ethell IM, Hagihara K, Schnaar RL, Ruoslahti E,
Yamaguchi Y: The proteoglycan lectin domain binds sulfated cell surface
glycolipids and promotes cell adhesion. J Biol Chem 274:11431-8, 1999
13. Yamada H, Fredette B, Shitara K, Hagihara K, Miura R, Ranscht B,
Stallcup WB, Yamaguchi Y: The brain chondroitin sulfate proteoglycan
brevican associates with astrocytes ensheathing cerebellar glomeruli and
inhibits neurite outgrowth from granule neurons. J Neurosci 17:7784-7795,
1997
14. Hagihara K, Wu-Peng XS, Funabashi T, Kato J, Pfaff DW: Nucleic acid
sequence and DNase hypersensitive sites of the 5' region of the mouse
progesterone receptor gene. Biochem Biophys Res Commun 205:1093-1101,
1994
15. Hirai M, Hirata S, Osada T, Hagihara K, Kato J: Androgen receptor mRNA
in the rat ovary and uterus. J Steroid Biochem Mol Biol 49:1-7, 1994
16. Osada T, Hirata S, Hirai M, Hagihara K, Kato J: Detection and levels of
androgen receptor messenger ribonucleic acid in the rat brain by means of
reverse transcription-polymerase chain reaction. Endocr J 40:439-446,
1993
17. Hagihara K, Hirata S, Osada T, Hirai M, Kato J: Distribution of cells
containing progesterone receptor mRNA in the female rat di- and
telencephalon: an in situ hybridization study. Brain Res Mol Brain Res
14:239-249, 1992
18. Hagihara K, Hirata S, Osada T, Hirai M, Kato J: Expression of
progesterone receptor in the neonatal rat brain cortex: detection of its
mRNA using reverse transcription-polymerase chain reaction. J Steroid
Biochem Mol Biol 41:637-640,1992
19. Hirata S, Osada T, Hirai M, Hagihara K, Kato J: Expression of estrogen
receptor in the rat brain: detection of its mRNA using reverse
transcription-polymerase chain reaction. J Steroid Biochem Mol Biol
41:583-587,1992
20. Hagihara K, Shiosaka S, Lee Y, Kato J, Hatano O, Takakusu A, Emi Y,
Omura T, Tohyama M: Presence of sex difference of cytochrome P-450 in the
rat preoptic area and hypothalamus with reference to coexistence with
oxytocin. Brain Res 515:69-78,1990
PRESENTATIONS
1. Francesconi W, Canonigo-Repunte V, George O, Hagihara K, Van Der Stap
LD, Berton F, Mendoza-Fernandez V, Morales M, Sanna PP: HIV1 transgenic
(Tg) rats as model of neuroAIDS. Society for Neuroscience 37th Annual
Meeting, San Diego, CA, Nov. 5, 2007.
2. Sanna PP, Mendez-Diaz M, Boutrel B, Hagihara K, Morales M, Canonigo-
Repunte V: The brain proteoglycan syndecan-3 regulates cocaine intake.
Society for Neuroscience 36th Annual Meeting, Atlanta, GA, Oct. 15, 2006.
3. Hagihara K, Ke Y, Long S, Princen F, Feng GS: Analysis of Gab1 and Gab2
function in the brain using the knockout mice. Society for Neuroscience
35th Annual Meeting, Washington DC, Nov. 16, 2005.
4. Ke Y, Zhang EE, Hagihara K, Nguyen T, Feng GS: Regulation of growth
factor and integrin signaling in neural stem cells by Shp-2 tyrosine
phosphatase. Society for Neuroscience 34th Annual Meeting, San Diego, CA.
Oct. 26, 2004.
5. Hagihara K, Zhang EE, Liu JJ, Feng GS: Shp2 tyrosine phosphatase plays a
critical role in neuronal cell differentiation and migration. Society for
Neuroscience 34th Annual Meeting, San Diego, CA. Oct. 25, 2004.
6. Zhang EE, Chapeau EA, Hagihara K, Feng GS: Shp2 tyrosine phosphatase
controls energy and metabolism in the adult brain. Society for
Neuroscience 34th Annual Meeting, San Diego, CA. Oct. 27, 2004.
7. Hagihara K, Zhang EE, Liu JJ, Feng GS: Functional analysis of Shp2
tyrosine phosphatase in mammalian brain development. The 10th Meeting on
Protein Phosphorylation and Cell Signaling, San Diego, CA, Jun 26, 2004.
8. Zhang EE, Hagihara K, Feng GS: Shp2 is required for development of
mammalian CNS. Society for Neuroscience 33th Annual Meeting, New Orleans,
LA. Nov. 8, 2003.
REFERENCES
1. Prof. Phil Baran (Scripps Research Institute)
E-mail: abm30q@r.postjobfree.com; Tel #: 858-***-****
2. Prof. Gen-Sheng Feng (UCSD, Dept. of Pathology)
E-mail: abm30q@r.postjobfree.com
3. Prof. Barbara Ranscht (Burnham Institute for Medical Research)
E-mail: abm30q@r.postjobfree.com; Tel #: 858-***-****
Contact this candidate