Carolyn Fisher

EDUCATION:

B.S. Biomedical Science -  Texas A&M University - May 1979

Completed graduate course work pursuant to an M.S. degree in Veterinary Toxicology at Texas A&M University

PREVIOUS WORK EXPERIENCE:

September 2002–September 2003 – Analyst IV - Cedra Corporation, In Vitro Division, Austin, Texas.
Responsible for isolation of hepatocytes from human or animal liver and preparation of hepatocyte product for sale.  Areas of research experience include: 1) portal vein cannulation and liver perfusion in rodents; 2) liver perfusion in dogs, monkeys, and humans; 3) assessment of hepatocyte  cytochrome P450 isoform activity by HPLC analysis of metabolites; 4) GLP documentation procedures; 5) specialized cell culture plate preparation in addition to general cell culture duties.

September 1997 - December 2001 -- Research Project Administrator - Dept. of Pharmaceutical Sciences, Texas Tech School of Pharmacy, Amarillo, Texas. Research duties include in situ brain perfusion studies involving transport of pharmaceutics across the blood-brain barrier and pharmacokinetic analysis of selected pharmaceutics in rats.   Areas of research experience include:  1)  small animal surgery to conduct carotid artery cannulation as well as femoral artery and vein cannulation;  2)  HPLC analysis of drugs in solution, tissues and plasma;  3)  dissection of brain tissue for solubilization and analysis by liquid scintillation counting; and 4) familiarity with SYBYL program for Comparative Molecular Field Analysis (CoMFA).  In addition to research duties, I have provided departmental support in the areas of 1) new laboratory design and construction; 2) core equipment purchases and maintenance; and 3) temporary departmental secretary.  

May 1992 - August 1997 -- Senior Research Associate - Green Center for Reproductive Biology Sciences, UT Southwestern Medical Center, Dallas, Texas. Laboratory manager responsible for supervising and  training graduate students and visiting scientists.   Additional responsibilities include supervising junior technical staff in the ordering of supplies and maintenance of equipment, initiating investigations into new areas of research, training and advising MD and postdoctoral fellows.  Areas of research experience include: 1) Characterization of knockout mouse strain, 2) Knockout vector construction, 3) Bacterial expression of proteins, 4) Western blot analysis, 5) Library screening, 6) PCR analysis of gene mutations, 7) Water assay for cytochrome P450 aromatase activity.  I also have familiarity with primary cell culture preparation.

June 1988 - June 1992 -- Research Associate -  Dept. of Biochemistry,   UT Southwestern Medical Center,  Dallas, Texas.  Conducted analysis of mutations in cell lines from maple syrup urine disease patients by PCR amplification and direct sequencing of exons from the affected subunit gene.  Additional duties include: 1) Maintaining fibroblast and lymphoblast cell  lines in tissue culture and harvesting cells using sterile and nonsterile techniques for RNA,  DNA, and Western blotting analysis, 2) Assaying new patient cell lines as received for branched chain alpha-keto acid dehydrogenase activity and reporting results to clinicians, 3) Processing harvested cells to collect genomic DNA ,  total RNA, and polyA RNA,  and 4) Maintaining the cell bank.  I also have experience in allele specific oligonucleotide hybridizations, transfections, southern blotting, and  Epstein Barr viral transformation of B lymphocytes.

October 1987 -  June 1988 --  Toxicologist -  PPG Industries, Inc.,  Coatings & Resins  Division,  Environmental Sciences Center, RIDC Park, Pittsburgh,  Pennsylvania.  Performed Ames bacterial mutagenicity assay under EPA GLP's with samples from C&R.   Collected and analyzed data from both activated and nonactivated assays and prepared reports using a VAX mainframe computer.  Additional duties involved maintenance of bacterial stocks and confirmation of each strain's genetic identity.  Utilized RS/1 on the VAX for data analysis.

July 1984 -  October 1987 --  Toxicologist -  PPG Industries, Inc., Chemicals Division, Barberton Technical Center, Barberton, Ohio. Responsibilities included:  1) Auditing and monitoring toxicology studies conducted under EPA GLP's at contract laboratories, 2) Assisting in protocol design and review of reports from toxicology studies supporting registration of herbicides under FIFRA regulations, 3) Interacting with analytical personnel in organization and conduct of sample analysis from toxicology studies, 4) Writing reports concerning analytical results from sample analysis, 5) Organizing strategies for literature surveys relevant to current issues in toxicology.  I am familiar with mainframe computers such as the HP3000 and microcomputers.

October 1983 - July 1984 -- Research Technician - PPG Industries, Inc., Chemicals Division, Barberton Technical Center, Barberton, Ohio. Assisted in conducting plant metabolism studies designed to support registration of herbicides under FIFRA regulations.  Utilized thin layer and column chromatographic techniques in conjunction with liquid scintillation counting and autoradiographic techniques to identify metabolites formed in various crops after experimental herbicide treatment.  Also assisted in conducting translocation and dissipation studies.

August 1983 - October 1983 -- Technician - PPG Industries, Inc., Chemicals Division, Barberton Technical Center, Barberton, Ohio. Analyzed soil and water samples for mercury content using acid digestion and cold vapor atomic absorption.

July 1981 - October 1982 -- Technician I - USDA Veterinary Toxicology and Entomology Research Laboratory, College Station, Texas. Conducted experiments to characterize glycosyl transferases from insects.  Performed product analysis of insect chitin synthase enzyme system.    

September 1979 - July 1981 -- Teaching Assistantship - Department of Veterinary Pathology, Texas A&M University, College Station, Texas. Responsibilities included preparing laboratory for class sessions and assisting students in staining and interpreting peripheral blood smears, bone marrow smears, and vaginal cytology smears.  Also assisted students in performing and assessing other hematology parameters, urinalysis, and clinical chemistry assays.

Summers between regular semester undergraduate course work, 1975 - 1979.

Summer 1979 - Laboratory Secretary - Spring Branch Memorial Hospital, Houston, Texas.

Summer 1978 - Courier - Pathology Labs of Houston, Houston, Texas.

Summer 1977 - Receptionist - Gessner Road Animal Hospital, Houston, Texas.

Summer 1976 - Receptionist - Campbell Road Animal Hospital, Houston, Texas.

PUBLICATIONS

Agarwal, V.R., Sinton, C.M., Liang, C-L., Fisher, C., German, D. C., and Simpson, E.R. (2000)  Upregulation of estrogen receptors in the forebrain of aromatase knockout (ArKO) mice.  Mol Cell Endo  162: 9-16.

Oz, O.K., Zerwekh, J.E., Fisher, C., Graves, K., Nanu, L., Millsaps, R., and Simpson, E.R. (2000) Bone has a sexually dimorphic response to aromatase deficiency.  J. Bone & Miner Res  15(3): 507-14.

Robertson, K.M., O’Donnell, L., Jones, M.E., Meachem, S.J., Boon, W.C., Fisher, C.R., Graves, K.H., McLachlan, R.I., and Simpson, E.R.  (1999)  Impairment of spermatogenesis in mice lacking a functional aromatase (CYP 19) gene.  Proc Natl Acad Sci USA 96(14): 79861-91. 

Bulun, S.E., Noble, L.S., Takayama, K., Michael, M.D., Agarwal, V., Fisher, C., Zhao, Y., Hinshelwood, M.M., Ito, Y., and Simpson, E.R.  (1997)Endocrine disorders associated with inappropriately high aromatase expression. J. Steroid Biochem Mol Biol  61(3-6): 133-9.

Simpson, E.R., Zhao, Y., Agarwal, V.R., Michael, M.D., Bulun, S.E., Hinshelwood, M.M., Graham-Lorence, S.,  Sun, T., Fisher, C.R., Qin, K., and Mendelson, C.R. (1997)  Aromatase expression in health and disease.  Recent Progress in Hormone Research 52, 185-214.

Morishima, A., Grumbach, M.M., Simpson, E.R., Fisher, C.R., and Qin, K.(1995) Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. (80),  3689-3698.

Simpson, E.R., Mahendroo, M.S., Means, G.D., Kilgore, M.W., Hinshelwood, M.M., Graham-Lorence, S., Amarneh, B., Ito, Y., Fisher, C.R.,  Michael, M.D., Mendelson, C.R., and Bulun, S.E.(1994) Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis.  Endocrine Rev. 15, 342-355.

Chuang, J.L., Fisher, C.R., Cox, R.P., and Chuang, D.T.(1994)  Molecular basis of maple syrup urine disease:  novel mutations at the E1  locus that impair E1( 2 2) assembly or decrease steady-state E1  mRNA levels of branched-chain  -keto acid dehydrogenase complex.  Am J Human Genetics 55(2), 297-304.

Fisher, C.R., Ito, Y., Conte, F.A.,  Grumbach, M.M., and Simpson, E.R. (1994) The molecular basis of aromatase deficiency in an adult female due to mutations in the CYP19 gene.  Cytochrome P450. 8th International Conference.  M.C. Lechner, Ed., Eurotext, Paris, 535-538.

Conte, F.A., Grumbach, M.M., Ito, Y., Fisher, C.R., and Simpson, E.R.(1994) A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom).  J Clin Endocrinol Metab. 78, 1287-1292.

Ito, Y., Fisher, C.R.,  Conte, F.A.,  Grumbach, M.M.,  and Simpson, E.R.(1993)  Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries.  Proc. Natl. Acad. Sci. USA 90,11673-11677. 

Fisher, C.W., Fisher, C.R., Chuang, J.L., Lau, K.S.,  Chuang, D.T.  and Cox, R.P. (1993)  Occurrence of a two base pair  (AT) deletion  allele and a  nonsense (G to T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease. Am. J. Human Genetics 52, 414-424.

Fisher, C.W., Lau, K.S., Fisher, C.R., Wynn, R.M., Cox, R.P. and Chuang, D.T. (1991) A 17-bp insertion and a Phe215->Cys missense mutation in the dihydrolipoyl transacylase (E2) mRNA from a thiamine-responsive maple syrup urine disease patient WG-34. Biochem. Biophys. Res. Comm. 174, 804-809.

Fisher, C.R., Chuang, J.L., Star, R., Fisher, C.W., Cox, R.P. and Chuang, D.T. (1991) Maple syrup urine disease in Mennonites: Evidence that the Y393N mutation in E1  impedes assembly of the E1 component of branched-chain  -keto acid dehydrogenase complex. J. Clin. Invest.  88, 1034-1037.

Fisher, C.R., Fisher, C.W., Chuang, D.T. and Cox, R.P. (1991) Occurence of a Tyr393->Asn (Y393N) mutation in the E1  gene of the branched-chain  -keto acid dehydrogenase complex in maple syrup urine disease patients from a Mennonite population. American J. Human Genetics 49, 429-434.

Ross, J.H. and Fisher,  C.R.  (1988) Pharmacokinetics of lactofen and metabolites in the mouse, rat, rhesus monkey, and chimpanzee. The Toxicologist, Vol. 8, No. 1.

Leber, P. , Fisher, C., Couch,  R., Erickson, M., Butler, E.,  Maruyama,  H. and Williams, G. (1988) Liver effects of lactofen (Cobra Herbicide) in rats and chimpanzees.  The Toxicologist, Vol. 8, No. 1.

MEETING ABSTRACTS: 

Smith, Q.R., Fisher, C., Liu, X., and Allen, D.D. (2001) Role of active efflux in the brain distribution of chlorambucil across the blood-brain barrier.  2001 Annual Meeting of the American Association of Pharmaceutical Scientists,

Smith, Q.R., Fisher, C.R., and Liu X. (2000) Brain uptake of the lipophilic anticancer drug chlorambucil - limitation by plasma protein binding.  2000 Annual Meeting of the American Association of Pharmaceutical Scientists, October 29--November 2, 2000.

Heuerman, J.S., Fisher, C.R., Allen, D.D., and Smith, Q.R. (2000) Binding site model of the cerebrovascular large neutral amino acid transporter (LAT1) for brain drug delivery.  2000 Annual Meeting of the American Association of Pharmaceutical Scientists, October 29--November 2, 2000.

Oki, J., Fisher, C., and Smith, Q.R. (1999) Brain and plasma pharmacokinetics of metasarcolysin and melphalan, two drugs that are shuttled into brain by the large neutral amino acid transporter of the blood-brain barrier.  1999 Annual Meeting of the American Association of Pharmaceutical Scientists, November 14-18, 1999.

Smith, Q.R., Fisher, C., Allen, D., and Oki, J. (1998) Development of a novel screening method to predict brain availability to drugs that bind highly to plasma proteins. 1998 Annual Meeting of the American Association of Pharmaceutical Scientists, November 15-19, 1998.

Fisher, C.R., Graves, K., and Simpson, E.R. (1997) Characterization of aromatase-deficient (ArKO) mice due to targeted disruption of the CYP19 gene.  79th Annual Meeting of The Endocrine Society, June 11-14, 1997. 

Graves, K., Fisher, C.R., Mendelson, C.R., and Simpson, E.R. (1997) The role of estrogen in the skin: lessons from aromatase knockout (ArKO) and transgenic mice.  79th Annual Meeting of The Endocrine Society, June 11-14, 1997.  

Sun, T., Zhao, Y., Fisher, C.R., Kilgore, M.K., Mendelson, C.R., and Simpson, E.R. (1996) Characterization of cis-acting elements of the human aromatase P450 (CYP19) gene that mediate regulation by retinoids in human choriocarcinoma cells.  10th International Congress of Endocrinology, June 12-15, 1996.

Qin, K., Fisher, C.R., Simpson, E.R., Serpente, S., Faustini-Fustini, M., and Carane, C. (1996) Oligospermia and persistent linear growth of a male subject caused by a missense mutation in the gene encoding aromatase.  10th International Congress of Endocrinology, June 12-15, 1996.

Qin,K., Fisher,C.R., Grumbach, M.M., Morishima, A., and Simpson, E.R. (1995) Aromatase deficiency in a male subject: characterization of a mutation in the CYP19 gene in an affected family.   77th Annual Meeting of The Endocrine Soiciety, June 9--12, 1995.

Fisher, C.R., Fisher, C.W., Chuang, D.T. and Cox, R.P. (1991) Occurence of a Tyr393 to Asn mutation in exon 9 of the E1  gene of the branched chain  -keto acid dehydrogenase complex in Mennonite maple syrup urine disease patients. FASEB J. 4806.

Fisher, C.W., Lau, K.S., Fisher, C.R., Cox, R.P. and Chuang, D.T. (1991) Identification of mutations in the dihydrolipoyl transacylase (E2) subunit of the branched chain  -keto acid dehydrogenase complex. FASEB J. 480.

EMAIL ADDRESS:  crfisher@mail.utexas.edu