Education

• B.A. Biology (1979)
  Chemistry Point Loma College, San Diego, Calif.

• Ph.D. Molecular Biology (1986)
  The Johns Hopkins University School of Medicine, Baltimore, Md.

• Postdoctorate Molecular Biology (1986 to 1990)
  The Salk Institute, La Jolla

Professional experience

• 2000 to present: Associate professor, Department of Human & Molecular Genetics, Virginia Commonwealth University, Richmond
• 1999 to 2000: Full member, Department of Basic Research, Cancer Therapy and Research Center, San Antonio, Texas
• 1996 to 2000: Associate professor, Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio
• 1995 to 1999: Associate director, Department of Cancer Biology, Cancer Therapy and Research Center, San Antonio
• 1990 to 1996: Assistant professor, Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio
• 1990 to 1995: Assistant member, Department of Cancer Biology, Cancer Therapy and Research Center, San Antonio, Texas

Honors

• 1998 to 2000: John E. Freeman, M.D., Endowed Chair in Cancer Biology, Cancer Therapy and Research Center, San Antonio, Texas
• 1994: Point Loma College Distinguished Alumnus Award
• 1989 to 1990: American Cancer Society California Chapter Senior Postdoctoral Fellowship
• 1986 to 1989: American Cancer Society Postdoctoral Fellowship
• 1982: ARCS (Achievement Rewards for College Scientists) Foundation Scholarship Award
• 1979: Graduated Valedictorian, Summa Cum Laude from Point Loma College

Funded research

• Mechanisms of Ras Control of Mammary Tumor Properties in Transgenic Mice, U.S. Department of Defense
• Osteoclasts from Transgenic Mice, University of Texas Health Science Center, San Antonio (Jolene J. Windle)

Research interests

The primary goal of the research in this laboratory is to understand the role of various genetic alterations in tumorigenesis and tumor properties, using a variety of genetically engineered mouse tumor models. One major project has focused on an investigation of the role of the p53 tumor suppressor gene in cell cycle control, apoptosis and genomic instability in mouse mammary/salivary tumor models. MMTV-ras and p53-/- mice have been interbred to generate mice that develop tumors in a wild type or p53-deficient background, and tumor properties, including response to chemotherapy, in mice of these two classes have been compared. These studies are currently being extended to examine the differences between specific p53 mutations on tumor properties. Additional mouse tumor models being examined include MMTV-myc and MMTV-mycXras transgenic mice, as well as MMTV-ras/p21WAF1-/- and MMTV-ras/p16INK4a/p19ARF-/- mice. Another major focus of the lab at present involves the creation and characterization of transgenic mice expressing various raf1 and PI3K mutants in an effort to identify the specific ras signaling pathways mediating various tumor properties, particularly the marked resistance to apoptosis observed in MMTV-ras tumors. Finally, a new research direction involves the use of DNA microarrays and other methods of gene expression profiling in an attempt to identify gene expression "fingerprints" in transgenic mouse tumors that correlate with specific tumor properties.

Publications

• Petit T, Bearss DJ, Troyer DA, Munoz RM, Windle JJ (Submitted) p53-independent response to cisplatin and oxaliplatin in MMTV-ras mouse salivary tumors.
• Bearss DJ, Lee RJ, Munoz RM, Troyer DA, Pestell RG, Windle JJ (Submitted)Comparison of tumorigenesis and tumor properties in MMTV-ras mice lacking p21WAF1/CIP1 and p53.
• Bearss DJ, Lee RJ, Troyer DA, Pestell RG, Windle JJ, (in press) p21WAF1/CIP1 deficiency has opposite effects on tumor cell proliferation, CDK activity and cyclin levels in mammary tumors from MMTV-ras and MMTV-myc mice Cancer Res.
• Bearss DJ, Subler MA, Hundley JE, Troyer DA, Salinas RA, Windle JJ (2000) Genetic determinants of response to chemotherapy in transgenic mouse mammary and salivary tumors. Oncogene 19:1114-1122.
• D'errico, J.A., Berry, J.E., Hongjiao, O., Strayhorn, C.L., Windle, J.J., Somerman, M.J. Employing a transgenic animal model to obtain cementoblasts in vitro. J. Periodontol., 71:63-72, 2000.
• Mills MD, Windle JJ, Albert DM (1999) Retinoblastoma in transgenic mice: models of hereditary retinoblastoma. Survey Ophthalmol 43:508-518.
• Rowinsky EK, Windle JJ, Von Hoff DD (1999) Ras protein farnesyltransferase: a strategic target for anticancer therapeutic development. J Clin Oncol 17:3631-3652.
• Syed NA, Windle JJ, Darjatmoko SR, Lokken JM, Steeves RA, Chappell R, Wallow IHL, Koop BA, Mangold G, Howes KA, Albert DM (1998) Characterization of transgenic mice with pigmented intraocular tumors: tissue of origin and response to treatment. Invest Ophthalmol Vis Sci 39:2800-2805.
• Hentunen TA, Reddy SV, Boyce BF, Devlin R, Park, H-R, Selander KS, Dallas M, Kurihara N, Galson D, Goldring SR, Koop BA, Windle JJ, Roodman GD (1998) Development of an osteoclast cell line by targeting of bcl-XL and Simian Virus 40 large T-antigen to the osteoclast lineage in transgenic mice. J Clin Invest 102:88-97.
• Engelman JA, Lee RJ, Karnezis A, Bearss DJ, Webster M, Siegel P, Muller WJ, Windle JJ, Pestell RG, Lisanti MP (1998) Reciprocal regulation of Neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. J Biol Chem 273 :20448-20455.
• Hopp RM, Ransom N, Hilsenbeck SG, Papermaster DM, Windle JJ (1998) Apoptosis in the Murine rd Retinal degeneration is predominantly p53-independent. Molecular Vision, http://www.emory.edu/molvis/v4/p5.
• Barrington RE, Subler MA, Rands E, Omer CA, Miller PJ, Hundley JE, Koester SK, Troyer DA, Bearss DJ, Conner MW, Gibbs JB, Hamilton K, Koblan KS, Mosser SD, O'Neill TJ, Schaber MD, Senderak ET, Windle JJ, Oliff A, Kohl NE (1998) A farnesyltransferase inhibitor induces tumor regression in transgenic mice harboring multiple oncogenic mutations by mediating alterations in both cell cycle control and apoptosis. Mol Cell Biol 18:85-92.
• Kato Y, Windle JJ, Koop BA, Mundy GR, Bonewald LF (1997) Establishment of an osteocyte-like cell line, MLO-Y4. J Bone Min Res 12:2014-2023.
• Hundley JE, Koester SK, Troyer DA, Hilsenbeck SG, Windle JJ (1997) Differential regulation of cell cycle characteristics and apoptosis in MMTV-myc and MMTV-ras mouse mammary tumors. Cancer Res 57:600-603.
• Hundley JE, Koester SK, Troyer DA, Hilsenbeck SG, Subler MA, Windle JJ (1997) Increased tumor proliferation and genomic instability without decreased apoptosis in MMTV-ras mice deficient for p53. Moll Cell Biol 17:723-731.
• Murray TG, Roth DB, O'Brien JM, Feuer W, Cicciarelli N, Markoe AM, Hernandez E, Smith BJ, Windle JJ (1996) Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma. Arch Ophthal 114:1385-1389.
• Murray TG, O'Brien JM, Steeves RA, Smith BJ, Albert DM, Cicciarelli N, Markoe AM, Tompkins DT, Windle JJ (1996) Radiation therapy and ferromagnetic hyperthermia in the treatment of murine transgenic retinoblastoma. Arch Ophthal 114:1376-1381.
• Harbour JW, Murray TG, Hamasaki D, Cicciarelli N, Hernandez E, Smith B, Windle J, O'Brien JM (1996) Local carboplatin therapy in transgenic murine retinoblastoma. Invest Ophthal Vis Sci 37:1892-1898.
• Alarid ET, Windle JJ, Whyte DB, Mellon PL (1996) Immortalization of Pituitary Cells at Discrete Stages of Development by Directed Oncogenesis in Transgenic Mice. Development, 122:3319-3329.
• Morgan WW, Walter CA, Windle JJ, Sharp ZD (1996) 3.6 Kilobases of the 5' Flanking DNA Mediate Brain-Specific but not Catecholaminergic-Specific Expression of the Mouse Tyrosine Hydroxylase Gene Promoter. J Neurochem 66:20-25.
• Ghosh-Choudhury N, Windle JJ, Koop BA, Harris MA, Guerrero DL, Wozney JM, Mundy GR, Harris SE (1996) Immortalized Murine Osteoblasts Derived from BMP2-T-Antigen Expressing Transgenic Mice. Endocrinology 137:331-339.
• Marcus DM, Lasudry JGH, Carpenter JL, Windle JJ, Howes KA, Al-Ubaidi MR, Baehr W, Overbeek PA, Font RL, Albert DM (1996) Trilateral Tumors in Four Different Lines of Transgenic Mice Expressing SV40 T-Antigen. Invest Ophthal Vis Sci 37:392-396.
• Chen D, Chen H, Feng JQ, Windle JJ, Koop BA, Harris MA, Bonewald LF, Boyce BF, Wozney JM, Mundy GR, Harris SE (1995) Osteoblastic Cell Lines Derived from a Transgenic Mouse Containing the Osteocalcin Promoter Driving SV40 T-Antigen. Mol Cell Diff 3:193-212.
• Boyce BF, Wright K, Reddy SV, Koop BA, Story B, Devlin R, Leach RJ, Roodman GD, Windle JJ (1995) Targeting SV40 T-antigen to the Osteoclast in Transgenic Mice Causes Osteoclast Tumors and Transformation and Apoptosis of Osteoclasts. Endocrinology 136:5751-5759.
• Schechter J, Stauber C, Windle JJ, Mellon PL (1995) Basic Fibroblast Growth Factor: The Neurotrophic Factor Influencing the Ingrowth of Neural Tissue into the Anterior Pituitary of ?-T7 Transgenic Mice? Neuroendocrinology 61:622-627.
• Reddy SV, Hundley JE, Windle JJ, Alcantara O, Linn R, Leach RJ, Boldt DH, Roodman GD (1995) Characterization of the Mouse Tartrate-Resistant Acid Phosphatase (TRAP) Gene Promoter. J Bone Min Res 10:601-606
• Papermaster DS, Windle JJ (1995) Death at an Early Age: Apoptosis in Inherited Retinal Degenerations. Invest. Ophthal. and Vis. Sci., 36:977-983.
• Mellon PL, Eraly SA, Belsham DD, Lawson MA, Clark ME, Whyte DB, Windle JJ (1995) An Immortal Cell Culture Model of Hypothalamic Gonadotropin-Releasing Hormone Neurons. METHODS: A Companion to Methods in Enzymology 7:303-310.
• Albert DM, Griep AE, Lambert PF, Howes KA, Windle JJ, Lasudry JGH (1994) Transgenic Models of Retinoblastoma: What They Tell Us About Its Cause and Treatment. Trans. Am. Ophthalmol. Soc., 92:385-401
• Howes KA, Ransom N, Papermaster DS, Lasudry JGH, Albert DM, Windle JJ (1994) Apoptosis or Retinoblastoma: Alternative Fates of Photoreceptors Expressing the HPV16-E7 Gene in the Presence or Absence of p53. Genes and Devel 8:1300-1310.
• Howes KA, Lasudry JGH, Albert DM, Windle JJ (1994) Photoreceptor Cell Tumors in Transgenic Mice. Invest Ophthal Vis Sci 35:342-351.
• Reddy SV, Scarcez T, Windle JJ, Leach RJ, Hundley JE, Chirgwin JM, Chou JY, Roodman GD (1994) Cloning and Characterization of the 5'-Flanking Region of the Mouse Tartrate-Resistant Acid Phosphatase (TRAP) Gene. J. Bone and Min. Res., 8:1263-1270.
• Leach RJ, Reus BE. Hundley JE, Johnson-Pais TL, Windle JJ (1994) Confirmation of the Assignment of the Human Tartrate-Resistant Acid Phosphatase Gene (ACP5) to Chromosome 19 Genomics, 19:180-181, 1994.
• Bignon Y-J, Chen Y, Chang C-Y, Riley DJ, Windle JJ, Mellon PL, Lee W-H (1993) Expression of a Retinoblastoma Transgene Results in Dwarf Mice. Genes and Devel 7:1654-1662.
• Grimes R, Sakamuri RV, Leach RJ, Thierry S, Roodman GD, Lalley PA, Sakaguchi AY, Windle JJ (1993) Chromosomal Assignment in Mouse of the Tartrate-Resistant Acid Phosphatase Gene. Genomics 15:421-422.
• Schechter J, Windle JJ, Stauber C, Mellon PL (1992) Neural Tissue Within Anterior Pituitary Tumors Generated by Oncogene Expression in Transgenic Mice. Neuroendocrinology 56:300-311.
• Horn F, Windle JJ, Barnhart KM, Mellon PL (1992) Tissue-Specific Gene Expression in the Pituitary: The Glycoprotein Hormone ?-Subunit Gene is Regulated by a Gonadotrope-Specific Protein. Mol Cell Biol 12:2143-2153.
• Horn F, Bilezikjian LM, Perrin MH, Bosma MM, Windle JJ, Hille B, Vale W, Mellon PL (1991) Intracellular Responses to GnRH in a Clonal Cell Line of the Gonadotrope Lineage. Mol Endocrin 5:347-355.
• Sealfon SC, Gillo B, Mundamattom S, Mellon P, Windle JJ, Landau E, Roberts JL (1990) Gonadotropin-Releasing Hormone Receptor Expression in Xenopus Oocytes. Mol Endocrin 4:119-124.
• O'Brien JM, Marcus DM, Bernards R, Carpenter JL, Windle JJ, Mellon PL, Albert DM (1990) A Transgenic Mouse Model for Trilateral Retinoblastoma. Arch Ophthal 108:1145-1151.
• Mellon PL, Windle JJ, Goldsmith P, Padula C, Roberts J, Weiner RI (1990) Immortalization of Hypothalamic Neurons by Genetically Targeted Tumorigenesis. Neuron 5:1-10.
• Windle JJ, Weiner RI, Mellon PL (1990) Cell Lines of the Pituitary Gonadotrope Lineage Derived by Targeted Oncogenesis in Transgenic Mice. Mol Endocrin 4:597-603.
• Windle JJ, Albert DM, O'Brien JM, Marcus DM, Disteche CM, Bernards R, Mellon PL (1990) Retinoblastoma in Transgenic Mice. Nature 343:665-669.
• Windle JJ, Pape LK, Sollner-Webb B (1990) Half Helical Turn Spacing Changes Convert a Frog into a Mouse rDNA Promoter: A Distant Upstream Domain Determines the Helix Face of the Initiation Site. Genes and Devel 4:52-62.
• O'Brien JM, Marcus DM, Niffenegger AS, Bernards R, Carpenter JL, Windle JJ, Mellon P, Albert D.M (1989) Trilateral Retinoblastoma in Transgenic Mice. Tr Am Ophth Soc 87:301-326.
• Pape LK, Windle JJ, Mougey EB, Sollner-Webb B (1989) The Xenopus laevis rDNA 60/81 bp Repeats are Position Dependent Enhancers that Function at the Establishment of the Preinitiation Complex: Analysis in vivo and in an Enhancer-Responsive in vitro Sys tem. Mol Cell Biol 9:5093-5104.
• Windle JJ, Sollner-Webb B (1986) Two Distinct and Precisely Positioned Domains Promote Transcription of Xenopus laevis rRNA Genes: Analysis with Linker-Scanning Mutants. Mol Cell Biol 6:4585-4593.
• Windle JJ, Sollner-Webb B (1986) Upstream Domains of the Xenopus laevis rDNA Promoter are Revealed in Microinjected Oocytes. Mol Cell Biol 6:1228-1234.
• Windle JJ, Shin HS, Morrow JF (1984) Induction of Interleukin 1 Messenger RNA and Translation in Oocytes. J Immunol 132:1317-1322.
• Pearson WR, Windle JJ, Morrow JF, Benson AM, Talalay P (1983) Increased Synthesis of Glutathione S-Transferases in Response to Anticarcinogenic Antioxidants: Cloning and Measurement of Messenger RNA. J Biol Chem 258:2052-2062.