University of Oklahoma Health Sciences Center
Department of Obstetrics and Gynecology
Section of Gynecologic Oncology
P.O. Box 26901, WP2470
Oklahoma City, OK 73190
E-MAIL: Doris-Benbrook@ouhsc.edu
PHONE: (405) 271-5523
FAX: (405) 271-2968
1977 to 1981 North Central College, Naperville, IL
Bachelor of Arts, majors in Biology and Chemistry, minor in German.
1981 to 1985 Loyola University Medical Center
2001 South First Ave.
Maywood, IL 60101
Ph.D. in Biochemistry, Mentor: Robert V. Miller, Ph.D.
1985 to 1988, In the laboratory of Magnus Pfahl, Ph.D.
La Jolla Cancer Research Foundation, 10901 North Torrey Pines Road, La Jolla, CA 92037
1988 to 1991, In the laboratory of Nicholas C. Jones, Ph.D.
Imperial Cancer Research Fund, P.O. Box 123, 44 Lincolns Inn Fields, London WC2A. 3PX
Associate Professor and Director of Research 1997-present
Assistant Professor 1991-1997
Director of Research 1993-present
Section of Gynecologic Oncology Department of Obstetrics and Gynecology
University of Oklahoma College of Medicine
Adjunct Associate Professor 1997-present
Adjunct Assistant Professor 1993-1997
Adjunct Faculty Committee 1998-present
Department of Biochemistry and Molecular Biology
University of Oklahoma College of Medicine
Associate Member of the Graduate Faculty,1993-present
University of Oklahoma College of Medicine
Vice Chair of the Institutional Biosafety Committee (IBC), 1995-present
University of Oklahoma Health Sciences Center
Member of the Patent Advisory Committee, 1998-01
University of Oklahoma
National Cancer Institute (NCI) Special Reviewer for "Chemoprevention in Genetically-Identified High-Risk Groups: Interactive Research and Development Projects".
National Cancer Institute (NCI), Site Visit Reviewer, June 1999.
Department of Veterans Affairs’ Medical Research Branch ad hoc grant reviewer.
Ad Hoc reviewer for American Journal of Obstetrics and Gynecology, Journal of Biochemistry, Blood, Experimental Cell Research, Journal of Surgical Oncology.
Co-inventor on a patent application "Novel Orphan Receptor Interacting With Retinoid/Thyroid Hormone Receptor Subfamily" (Ref. No. 1212.017)
Co-inventor on "Heteroarotinoids-Anticancer Agents with Receptor Specificity and TGase Activity".
CURRENT FUNDING
National Cancer Institute, National Institutes of Health "Biological Activity of Heteroarotinoids." 08/01/96 - 11/30/99 $981,456 direct, $170,000 indirect. Principal Investigator: Eldon C. Nelson, Ph.D., Oklahoma State University Co-investigator Doris M. Benbrook: 08/01/96 - 12/01/99 $269,761 direct, $124,190 indirect
Mary Kay Ash Charitable Foundation "Development of Retinoids and Response Biomarkers for Ovarian Cancer." Principal Investigator: Doris M. Benbrook, Ph.D. 07/01/98 - 06/30/00 $90,864 direct, $9,136 indirect
National Cancer Institute, National Institutes of Health "Mechanism & Potential of Retinoid & DNA Damage Therapy." Principal Investigator: Doris M. Benbrook, Ph.D. 07/01/99 – 06/30/02 $306,562 direct, $134,145 indirect
American Institute for Cancer Research (AICR) "Ligand Activation of Peroxisome Proliferator-Activated Receptors in Rodent Mammary Tumor Models." Principal Investigator: Stephen Glore, Ph.D. Collaborator: Doris M. Benbrook, Ph.D. 01/01/98-01/01/00 $100,000
Procter and Gamble Consultantation and Research contract "Determination of Retinoid Receptor Transactivation Properities" 07/01/99 – 09/01/99, $8890
Department of Medicine OUHSC, 1999-2002 "Development of Immunotoxin for Ovarian Cancer" Seed money to mentor research project of Raffit Hassan, MD.
Cancer Research Foundation of America (CRFA) Fellowship "Human Papillomavirus and Epidermal Growth Factor Receptor as Biomarkers of Retinoid Cervix Cancer Chemoprevention" Principal Investigator: Doris M. Benbrook, Ph.D. Postodoctroal Fellow: Shennan Lu 01/15/00 - 01/14/02 $60,000
PAST GRANT FUNDING
American Institute of Cancer Research, 94A63 "Carotenoid Effects on Transcription and Growth in Tumors." 07/01/94 - 06/30/96 $100,000 direct, $10,000 indirect. Principal Investigator: Doris M. Benbrook
The Presbyterian Health Foundation, "Radiation and Retinoid Effects on Cervical Cancer." 01/01/94 - 01/01/95 $25,000 direct. Principal Investigator: Doris M. Benbrook, Ph.D.
National Science Foundation, MCB-9209479, "DNA Binding Specificities of cJun Dimers." 08/01/92 - 01/31/94 $16,200, $1,800 indirect. Principal Investigator: Doris M. Benbrook, Ph.D.
Milheim Foundation for Cancer Research, 92-14, "Retinoids, cJun and Cervical Cancer." 07/01/92 - 06/30/93 $14,000 direct . Principal Investigator: Doris M. Benbrook, Ph.D.
Oklahoma Medical Alumni Association, "Retinoids, cJun and Cervical Cancer." 09/01/92 - 08/31/93 $20,000 direct awarded, $11,000 accepted due to overlap with other funding.
Presbyterian Health Foundation, Research Equipment Repair Fund, 1992, $5,000 for repair of an ultracentrifuge.
ASCO trainer in Cancer Genetics
Integrated Graduate Student Curriculum
Biochemistry 6234: 4 hours of lectures on DNA tumor viruses and Chemical Carcinogenesis.
Biochemistry 5224: 2 hours of lectures on DNA Sequencing and EMSA.
Biochemistry 6224: 7 week laboratory rotations for Graduate Students.
Biochemistry 6980: Chair of Ph.D. thesis committee of Shennan Lu "Mechanism of Growth Inhibition by Retinoids".
Biochemistry 6980: Chair of Ph.D. thesis committe of Suresh Guruswamy.
Biochemistry 6502: Advanced Topics in Human Molecular Genetics, 2 hours
Biochemistry 5970: Student Research Seminar
Dental Biochemistry: Carcinogenesis, 1 hour
Ph.D. comprehensive qualifying written exams
Ph.D. comprehensive qualifying oral examination committees
Annual Lectures on Oncogenes and Tumor Supressor Genes in the Departments of Pathology and Radiobiology.
Todd Corn Biochemistry and Molecular Biology Ph.D., 1995
Kim Kyker Biochemistry and Molecular Biology Ph.D. candidate
Shankar Sachithanandam Radiological Sciences Ph.D. candidate
Shennan Lu Biochemistry and Molecular Biology Ph.D. candidate
Suresh Guruswamy Biochemistry and Molecular Biology Ph.D. candidate
1994-5 Evelyn Rosas Nuñez, M.D.
1995-6 Cole Flanagan, M.D.
1996-7 Jane Shen-Gunther, M.D.
1996-7 Paul A DiSilvestro, M.D.
1997-8 Todd Ivey, M.D.
1998-9 Michael Gold, M.D.
1999-0 Scott Kamelle, M.D.
Benbrook, D.M. and Miller, R.V. (1986) Effects of Norfloxacin on DNA metabolism in pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy, 29: 1-6.
Benbrook, D. & Pfahl, M. (1987) A Novel Thyroid Hormone Receptor Encoded by a cDNA Clone from a Human Testis Library. Science 238: 788-791.
Pfahl, M. & Benbrook, D. (1987) Nucleotide Sequence of cDNA Encoding a Novel Thyroid Hormone Receptor. Nucleic Acids Research 15: 9613.
Benbrook, D.M, Lernhardt, E. & Pfahl, M. (1988) A New Retinoic Acid Receptor Identified from a Hepatocellular Carcinoma. Nature, 333: 669-672.
Benbrook, D.M. & Jones, N.C. (1990) The Heterodimerization of Creb and Jun. Oncogene, 5: 295-302.
Benbrook, D.M. & Jones, N.C. (1994) Different Binding Specificities and Transactivation of Variant CRE's by CREB complexes. Nucleic Acids Research 22(8): 1463-1469.
Apfel, R., Benbrook, D.M, Lernhardt, E., Ortiz, M.A., and Pfahl, M. (1994) A novel orphan receptor with a unique ligand binding domain and its interaction with the retinoid/thyroid hormone receptor subfamily. Molecular and Cellular Biology, 14: 7015-7035.
Benbrook, D.M, Rogers, R., Medlin, M., and Dunn, S.T. (1995) Immunohistochemical anlaysis of differentiation and proliferation in organotypic cultures of cervical tumor cell lines. Tissue and Cell 27(3): 269-274.
Benbrook, D. M., Shen-Gunther, J., Nuñez, E.R., Dynlacht, J.R. (1997) Differential retinoic acid radiosensitization of cervical carcinoma cell lines. Clinical Cancer Research, 3: 939-945.
Johnson, G.A., Mannel, R.S., Khalifa, M., Walker, J.L., Wren, M., Min, K.-W., Benbrook, D.M. (1997) Epidermal growth factor receptor in vulvar malignancies and its relationship to metastatsis and patient survival. Gynecological Oncology, 65: 425-429.
Benbrook, D.M., Lu, S., Flanagan, C., Shen-Gunther, J., Angros, L.H., Lightfoot, S.A. (1997) Biological assay for activity and molecular mechanism of retinoids in cervical tumor cells. Gynecological Oncology, 66 :114-121.
Miller, A.M., Sahl, W.J., Brown, S.A., Young, S.K., Quinlan, C.M., Patel, P.R., Benbrook, D.M., Naylor, M.F. (1997) The role of human papillomavirus in the development of pyogenic granulomas. International Journal of Dermatology, 38: 101-105.
Benbrook, D.M., Madler, M.M., Spruce, L.W., Birckbichler, P., Nelson, E.C., Subramanian, S., Weerasekare, G.M., Gale, J.B., Patterson, Jr., M.K., Wang, B., Wang, W., Lu, S., Rowland, T.C., DiSilvestro, P., Berlin, K.D., Lindamood, C., Hill, D.L. (1997) Biologically active heteroarotinoids exhibit anticancer activity and decreased toxicity. Journal of Medicinal Chemistry, 40: 3567-3583.
Madler, M.M., Klucik, J., Soell, P.S., Brown, C.W., Liu, S., Berlin, K.D., Benbrook, D.M., Birckbichler, P.J., Nelson, E.C. (1998) Lithium hypochlorite-clorox as a novel oxidative mixture for methyl ketones and methyl carbinols. Organic Preparations and Procedures International, 30 : 230-234.
Benbrook, D.M., Subramanian, S., Gale, J.B., Liu, S., Brown, C.W., Boehm, M.F., Berlin, K.D. (1998) Synthesis and characterization of heteroarotinoids demonstrates structure-specificity relationships. Journal of Medicinal Chemistry, 41: 3753-3757.
DiSilvestro, P.A., Stanley, S.A., and Benbrook, D.M. (1999) Ki-67 expression in a cervical carcinoma organotypic model correlates with growth and EGF-R expression. Journal of the Lower Genital Tract Disease, 3: 1-5.
Waliszewski, P. Waliszewski, M., Gordon, N., Hurst, R.E., Benbrook, D.M., Dhar, A., Hemstreet, G.P. (1999) Retinoid signaling in immortalized and carcinoma-derived human uroepithelial cells. Molecular and Cellular Endocrinology, 148: 55-65.
Salsman, S., Lu, S., Benbrook, D.M. (1999) The mechanism of retinoid radiosensitization is independent of AP-1 repression in cervical carcinoma cells. Gynecologic Oncology, 73: 253-256.
Liu, S. Berlin, K.D., Simms-Kelley, M.D., Nelson, E.C., and Benbrook, D.M. (1999) Optimization and Synthesis of (E)-4-[2-(3,4-Dihydro-4,4-dimethyl-2h-1-benzopyran-6-yl)-1-propenyl]benzoic Acid-11-[14C]. Journal of Labelled Compounds and Radiopharmaceuticals, 42: 789-796.
Dhar,A., Liu,S., Berlin, K.D., Madler, M.M., Ivey, R.T., Birckbichler, P.J., Lu, S., Zacheis, D., Brown, C.W., Klucik, J., Nelson, E.C., Benbrook, D.M. Synthesis and Structure-Activity Relationships of Nitrogen Heteroarotinoids. Journal of Medicinal Chemistry, 42: 3602-3614.
Zacheis, D., Dhar, A., Lu, S., Madler, M.M., Klucik, J.Brown, C.w., Liu, S., Clement, F., Subramanian, S., Weerasekare, G.M., Berlin, K.D., Gold, M., Houck, J.R., Fountain, K.R., Benbrook, D.M (1999). Heteroarotinoids inhibit the growth of head and neck cancer cell lines in vitro and in vivo through both RAR and RXR retinoic acid receptors. Journal of Medicinal Chemistry, 42: 4234-4445.
Guruswamy, S., Lightfoot, S., Dhar, A., Hassan, R. Ivey, T.R., Benbrook, D.M. (1999) Induction of Apoptosis but not Differentiation Correlates with Growth Inhibition by Retinoids in Ovarian Adenocarcinoma Organotypic Cultures. Cancer Research, in preparation.
Dhar, A., Berlin, K.D., Benbrook, D.M. (1999) Inverse Agonism and Unique Activity Profile of a Heteroarotinoid. Journal of Biological Chemistry, in preparation.
Dhar, A., Ivey, T.R., Webster, M., Benbrook, D.M. (1999) Human Papillomavirus Antagonizes Retinoid Induction of Apoptosis in Cervical and Vulvar Carcinoma Cell Lines. Journal of Virology, in preparation.
Benbrook, D.M., Tonetti, D.A. & Miller, R.V. (1989) DNA Gyrase of Pseudomonas Aeruginosa: Inhibition by Quinolones. Proceedings International Telesymposium on Quinolones, Fernandez, P.B. (Ed.) J.R. Prous Science Publishers, pp.171-186.
Hurst, R. E., Waliszewski, P., Waliszewski, M., Bonner, R.B., Benbrook, D.M., Dhar, A., Hemstreet, III, G.P. (1998) Complexity, retinoid-responsive gene networks, and bladder carcinogenesis. Advances in Bladder Research, L. Baskin, ed. Plenum Press, N.Y., pp. 449-467.
Benbrook, D.M., Medlin, M., Rogers, R., Ahern-Moore, J., Dunn, S.T., Lord, B., Walker, J.L. (1993) "Retinoid effects on tumor cells in organotypic culture." American Association for Cancer Research Special Conference "Mechanism of Action of Retinoids, Vitamin D, and Steroid Hormones."
Benbrook, D. M., Heldermon, C., Nunez, E.R., and Waliszewski, P. (1994) Retinoic acid receptor RARb effects in cervical tumor cell lines. Diet and Cancer: Molecular Mechanisms of Interactions, American Institute of Cancer Research.
Benbrook, D. M., Heldermon, C. (1994) Retinoic acid receptors bind to HPV16LCR sequence and repress transcription indirectly through AP1 sites. Proceedings of the 13th International Papillomavirus Conference.
Mannel, R. S., Khalifa, M., Wren, M., Walker, J.L., Min, K.-W., Benbrook, D.M. (1994) Epidermal growth factor receptor in vulvar malignancies and its relationship to metastasis and patient survival. 26th Annual Society of Gynecologic Oncologists’ Meeting.
Waliszewski, P., Benbrook, D., Nasim, M., Hurst, R.E. (1995) "Human uroepithelial cells contain retinoid signaling pathways." Proceedings of the American Association for Cancer Research, 36:630.
Waliszewski, P., Benbrook, D., Blaszewski, M.K., Gupta, M., Drews, M., Hurst, R.E. (1995) The retinoic acid signaling pathway in normal and transformed human intestinal epithelial cells. Proceedings of the American Association for Cancer Research, 36:601.
Nuñez, E.R., Heldermon, C., Benbrook, D.M. (1995) Restoration of RARb expression and function in RARb -deficient cervical tumor cell lines has different effects depending on the intercellular environment. American Association for Cancer Research Conference "Mechanism of Action of Retinoids, Vitamin D and Steroid Hormones".
Nuñez, E.R., Benbrook, D. M. (1995) Retinoic acid receptor expression effects growth and retinoid sensitivity in cervical tumor cell lines. American Association for Cancer Research Conference "Molecular Biology of Cancer: Implications for Prevention and Therapy".
Nuñez, E.R., Benbrook, D.M., Berlin, K.D., Nelson, E.C. (1995) A heteroarotinoid affects growth and transactivation of a retinoic acid response element in cervical carcinoma cell lines. The FASEB Journal, 9(3, part 1): 985.
Benbrook, D. M., Jordan, T.L., Heldermon, C. and Robinson, K. (1995) Evaluation of endogenous retinoic acid receptor function in cervical tumor cells. Dietary Phytochemicals in Cancer Prevention and Treatment, 62.
Nuñez, E.R., Jordan, T.L., Benbrook, D.M. (1996) 13-Cis acid is a radiosensitizer of SiHa cervical carcinoma cell line. Proceedings of the American Association for Cancer Research. 37:4144.
Madler, M., Benbrook, D.M. Birckbichler, P.J., Nelson, E.C., Berlin, K.D. (1996) Biologically active heteroarotinoids. Presented at the Annual Meeting of the Medicinal Chemistry Division of the American Chemical Society, August 96.
Oian, X., Benbrook, D.M., Berlin, K.D., Cushman, J.C., Madler, M.M., Patrick, S.D., Simms, M.D., Nelson, E.S. (1996) Comparative effects of a diaryl heteroarotinoid and all-trans-retinoic acid on induction of differentiation. The FASEB Journal, 10:4390.
Benbrook, D.M., Lu, S., Flanagan, C.W., Jordan, T.L. (1996) Retinoids inhibit growth and activate endogenous receptors in a cervical tumor cell line. Presented at the 1996 FASEB Summer Research Conference on Retinoids.
Lu, S., Flanagan, C.W., Shen-Gunther, J., Benbrook, D.M. (1997) Biological assay for activity and molecular mechanism of retinoids in cervical tumor cells. Gynecologic Oncology, 64(2):312.
Flanagan, C., Fishburne, V.H., DiSilvestro, P. Nuñez, E.R., Benbrook, D.M. (1997) Mechanism of retinoid anc carotenoid growth inhibition of a cervical tumor cell line. Gynecologic Oncology, 64(2):357.
Benbrook, D.M., Lu, S. (1997) Retinoid regulation of endogenous receptors, growth and EGF-R in a cervical carcinoma cell line. Proceedings of the 88th Annual Meeting of the American Association for Cancer Research, 38:453, abstract #3032.
Benbrook, D.M., Nuñez, E.R. (1997) Differences in radiosensitization and cell cycle progression of cervical carcinoma cell lines. Proceedings of the 88th Annual Meeting of the American Association for Cancer Research, 38:44, abstract #296.
Benbrook, D.M., Berlin, K.D., Birckbichler, P.J. (1997) Correlation of transactivation with growth inhibition and transglutaminase induction by heteroarotinoids. Proceedings of the 88th Annual Meeting of the American Association for Cancer Research, 38:454, abstract #3037.
DiSilvestro, P., Flanagan, C., Angros, L., Benbrook, D. (1997) Decrease in Ki-67 and epidermal growth factor receptor expression correlates with retinoic acid induced growth inhibition in a cervical cancer cell line. Proceedings of the 88th Annual Meeting of the American Association for Cancer Research, 38:88, abstract #592.
Ivey, R. T., Brown, D., Berlin, K.D., Benbrook, D.M. (1998) Retinoid response of two ovarian carcinoma cell lines. Proceedings of the American Association for Cancer Research, 39:106-107, abstract #722.
Lu, S., Dhar, A., Ivey, R.T., Berlin, K.D., Benbrook, D.M. (1998) Heteroarotinoid structure affects receptor specificity and growth inhibitory activities. Proceedings of the American Association for Cancer Research, 39:107, abstract #723.
Zacheis, D.H., Houck, J.R., Berlin, K.D., Benbrook, D.M. (1998) Inhibition of the growth of head and neck squamous cell carcinoma by heteroarotinoids. Fifth Research Workshop on the Biology, Prevention, and Treatment of Head and Neck Cancer, Abstract #130.
Simms-Kelley, M. D., Subramanian, S., Spruce, L. W., Madler, M. M., Patrick, S. D., Grummer, R., Lemire, T. D., Benbrook, D. M., Birckbichler, P. J., Berlin, K. D., and Nelson, E. C. Growth promoting activity of heteroarotinoids in vitamin A deficient rats. FASEB J. 12: 450, 1998
Dhar, A., Berlin, K.D., Madler, M.M., Ivey, R.T., Birckbichler, P.J., Lu, S., Zacheis, D., and Benbrook, D.M. Flexible Nitrogen Heteroarotinoids: Receptor specificity and Therapeutic Potential in Epithelial Cancers. American Association for Cancer Research Annual Meeting, April 10-14, 1999, Philadelphia, Pennsylvania.
Simms-Kelley, M. D., Subramanian, S., Madler, M. M., Patrick, S. D., Klucik, J., Browth, C. E., Liu, S., Lemire, T. D., Benbrook, D. M., Birckbichler, P. J., Berlin, K. D., and Nelson, E. C. Heteroarotinoids promote growth in vitamin A-deficient rats. FASEB J. 13:647, 1999.
INVITED LECTURES
Department of Microbiology, Oklahoma State University
Department of Biochemistry and Molecular Biology, University of Oklahoma
Department of Biochemistry and Molecular Biology, Oklahoma State University
Science Forum, Combined NIH Training Grants Meeting
Oklahoma Memorial Research Foundation
Department of Anatomy, University of Oklahoma
Department of Pathology , University of Oklahoma
Premed Club, University of Oklahoma Undergraduate School, Norman, Oklahoma
November 1995, Obstetrics and Gynecology Grand Rounds, University of Oklahoma
The Science Forum at the Oklahoma Medical Research Foundation
Obstetrics and Gynecology Grand Rounds, University of Oklahoma
Cancer Conference at INTEGRIS Baptist Medical Center, Oklahoma City, Oklahoma
Drug Dynamic Institute, University of Texas at Austin, Texas
Womens Health Symposium, Marriot Hotel, Oklahoma City, Oklahoma
July 1998, Gynecological Oncology Group Semi-annual Meeting, Toronto, Ontario
Department of Cellular Biology, Lousiana State University, Shreveport, LA
Department of Biochemistry and Molecular Biology, University of Oklahoma HSC
Department of Cellular and Molecular Medicine, University of Ottawa, Ottowa, Ontario
Oklahoma Memorial Research Foundation, Oklahoma City, OK
Februrary 1999, Steroid Hormone Receptor Group, Oklahoma City, OK
Obstetrics and Gynecology Grand Rounds University of Oklahoma HSC