Timothy F. Lane, Ph.D.

Laboratory Address:
545 BSRB
615 Charles Young Dr. South.
Los Angeles, CA 90095

Mailing Address:
10833 Le Conte Ave
MC- 174017
Los Angeles, CA 90095

Office Address:
BSRB 549

Affiliations
Affiliations
Associate Professor, Obstetrics and Gynecology, Biological Chemistry
Member, Cell & Developmental Biology GPB Home Area, JCCC Cancer and Stem Cell Biology Program Area, Molecular Pharmacology GPB Home Area
Research Interests
Failure of various genetic control points during development, or later in life, are known to contribute to Breast Cancer, a disease which affects roughly one in eight women. During development, mammary epithelial cells undergo highly programmed pattern formation and terminal differentiation. These processes prepare the gland for milk production. Interestingly, terminal differentiation also functions to protect mammary epithelial cells from developing cancer. We use genetic analysis and developmental biology to identify genes that regulate mammary growth. In particular, we use genetic (e.g. transgenic and knockout methods) and molecular screens to identify key genes in mammary patterning and tumor development. We also use functional genomics (including ordered gene arrays, and functional screening strategies) to reveal new regulators of the process. Current projects in the lab focus on the BRCA1 tumor suppressor gene, the wnt family of signaling proteins, and the role of endothelial stem cells in tissue remodeling and tumor progression.
Biography

Timothy F. Lane, Ph.D., is an Associate Professor in the Department of Biological Chemistry and an appointment in the medical school in Gyn Oncology. His main research interests are related to defining the role of stem cells in breast cancer progression and the role of Wnt signaling in regulating various adult stem cell compartments in bone and breast biology. His work on endothelial stem cell function in breast cancer is funded by one NIH R01 grant, and a Lab Fees Grant from the University of California. He received his Ph.D. from the University of Washington (1992), and did postdoctoral training at Harvard Medical School, in Genetics. He moved to UCLA in 1998 and was was promoted to Associate Professor with tenure in 2006. He is a member of the Molecular Biology Institute (MBI) graduate committee and is Co-PI of the Cancer Cell Biology training grant. He is also a member of the Broad Stem Cell Institute, the Orthopeadic Research Institute and the Jonsson Comprehensive Cancer Center. Dr. Lane is a member of the Jonsson Comprehensive Cancer Center at UCLA where he is part of the Cancer Cell Biology Program Area and the Women's Cancers Program Area. He is also an active member of the Orthopedics Research Center, and the Molecular Biology Institute. Dr. Lane is Co-PI of the Tumor Cell Biology Training grant and serves on the Graduate Student Committee of the Molecular Biology Institute. He is also Director of the UCLA/Laser Scanning Cytometer Shared Instrument Facility and serves on UCLA?s Embryonic Stem Cell Research Oversight Committee and the Council on Research.

Publications
Roodhart Jeanine M L, He Huanhuan, Daenen Laura G M, Monvoisin Arnaud, Barber Chad L, van Amersfoort Miranda, Hofmann Jennifer J, Radtke Freddy, Lane Timothy F, Voest Emile E, Iruela-Arispe M Luisa Notch1 regulates angio-supportive bone marrow-derived cells in mice: relevance to chemoresistance. Blood. 2013; 122(1): 143-53.
Li Jau-Yi, Adams Jonathan, Calvi Laura M, Lane Timothy F, Weitzmann M Neale, Pacifici Roberto Ovariectomy expands murine short-term hemopoietic stem cell function through T cell expressed CD40L and Wnt10B. Blood. 2013; 122(14): 2346-57.
Li Jau-Yi, Adams Jonathan, Calvi Laura M, Lane Timothy F, DiPaolo Richard, Weitzmann M Neale, Pacifici Roberto PTH expands short-term murine hemopoietic stem cells through T cells. Blood. 2012; 120(22): 4352-62.
Adams Jessica R, Xu Keli, Liu Jeff C, Agamez Natalia M Ruiz, Loch Amanda J, Wong Ruth G, Wang Wei, Wright Katherine L, Lane Timothy F, Zacksenhaus Eldad, Egan Sean E Cooperation between Pik3ca and p53 mutations in mouse mammary tumor formation. Cancer research. 2011; 71(7): 2706-17.
Khialeeva Elvira, Lane Timothy F, Carpenter Ellen M Disruption of reelin signaling alters mammary gland morphogenesis. Development (Cambridge, England). 2011; 138(4): 767-76.
Krum Susan A, la Rosa Dalugdugan Esther de, Miranda-Carboni Gustavo A, Lane Timothy F BRCA1 Forms a Functional Complex with γ-H2AX as a Late Response to Genotoxic Stress. Journal of nucleic acids. 2010; 2010(4): .
Zovein Ann C, Luque Alfonso, Turlo Kirsten A, Hofmann Jennifer J, Yee Kathleen M, Becker Michael S, Fassler Reinhard, Mellman Ira, Lane Timothy F, Iruela-Arispe M Luisa Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism. Developmental cell. 2010; 18(1): 39-51.
Jiang Z, H Li, T DenG, JI Herschkowitz, JC Liu, VJ Weigman, GW Murrow, M-S Tsao, TF Lane, RD Cardiff, CM Perou, E Zacksenhaus Rb deletion in mammary stem/bi-potent progenitors induces tumors with features of luminal-B or basal-like/EMT tumors depending on p53 status. . Journal of Clinical Invest 2010; in press: .
Jiang Zhe, Deng Tao, Jones Robert, Li Huiqin, Herschkowitz Jason I, Liu Jeff C, Weigman Victor J, Tsao Ming-Sound, Lane Timothy F, Perou Charles M, Zacksenhaus Eldad Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status. The Journal of clinical investigation. 2010; 120(9): 3296-309.
Carey James R, Christian Laursen John, Glaser Steven D, Raphael Stephen, Miller Gregory H, Crawford John, Lane Timothy F, Liwang Patricia J, Hammond Kimberly, Groves Theodore, Pittet Jean-Francois, Stuart David, Kolaitis Phokion G, Serwer Laura, Chen Mengfei, Feer Kenneth University of California Research Seminar Network: a prospectus. PLoS biology. 2010; 8(1): e1000289.
Stevens Jennifer R, Miranda-Carboni Gustavo A, Singer Meredith A, Brugger Sean M, Lyons Karen M, Lane Timothy F Wnt10b deficiency results in age dependent loss of bone mass and progressive reduction of mesenchymal progenitor cells. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2010; 12(17): .
Morizono Kouki, Xie Yiming, Helguera Gustavo, Daniels Tracy R, Lane Timothy F, Penichet Manuel L, Chen Irvin S Y A versatile targeting system with lentiviral vectors bearing the biotin-adaptor peptide. The journal of gene medicine. 2009; 11(8): 655-63.
Liu Qinghai, Nguyen David H, Dong Qinghua, Shitaku Peter, Chung Kenneth, Liu On Ying, Tso Jonathan L, Liu Jason Y, Konkankit Veerauo, Cloughesy Timothy F, Mischel Paul S, Lane Timothy F, Liau Linda M, Nelson Stanley F, Tso Cho-Lea Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors. Journal of neuro-oncology. 2009; 94(1): 1-19.
Moraes Ricardo C, Chang Hong, Harrington Nikesha, Landua John D, Prigge Jonathan T, Lane Timothy F, Wainwright Brandon J, Hamel Paul A, Lewis Michael T Ptch1 is required locally for mammary gland morphogenesis and systemically for ductal elongation. Development (Cambridge, England). 2009; 136(9): 1423-32.
Terauchi Masakazu, Li Jau-Yi, Bedi Brahmchetna, Baek Ki-Hyun, Tawfeek Hesham, Galley Sarah, Gilbert Linda, Nanes Mark S, Zayzafoon Majd, Guldberg Robert, Lamar David L, Singer Meredith A, Lane Timothy F, Kronenberg Henry M, Weitzmann M Neale, Pacifici Roberto T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling. Cell metabolism. 2009; 10(3): 229-40.
Miranda-Carboni Gustavo A, Krum Susan A, Yee Kathleen, Nava Miguel, Deng Qiming E, Pervin Shehla, Collado-Hidalgo Alicia, Galic Zoran, Zack Jerome A, Nakayama Keiko, Nakayama Keiichi I, Lane Timothy F A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors. Genes & development. 2008; 22(22): 3121-34.
Iwatsuki K. HX Liu, A Grunder, MA Singer, TF Lane, R Grosschedl, C Mistretta, R Margolskee. Role of wnt and hedgehog signaling in taste bud development. Proc. Natl. Acad. Sci. USA. 2007; 104: 2253-8..
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Bennett CN, H Ouyang, YL Ma, Q Zeng, I Gerin, KM Sousa, TF Lane, V Krishnan, KD Hankenson, OA Macdougald Wnt10b increases postnatal bone formation by enhancing osteoblast differentiation. . J Bone Miner Res 2007; 22: 1924-32.
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Monvoisin A, Alva JA, Hofmann JJ, Zovein AC, Lane TF, Iruela-Arispe ML. VE-cadherin-CreERT2 transgenic mouse: a model for inducible recombination in the endothelium. Developmental Dynamics. 2006; 235: 3413-22.
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Bennett CN, Longo KA, Wright WS, Suva LJ, Lane TF, Hankenson KD, MacDougald OA Regulation of osteoblastogenesis and bone mass by Wnt10b. Proceedings of the National Academy of Sciences of the United States of America. . 2005; 102(9): 3324-9.
Chang SH, Ai Y, Breyer RM, Lane TF, Hla T The prostaglandin E2 receptor EP2 is required for cyclooxygenase 2-mediated mammary hyperplasia. Cancer research. . 2005; 65(11): 4496-9.
Vertino AM, Taylor-Jones JM, Longo KA, Bearden ED, Lane TF, McGehee RE, MacDougald OA, Peterson CA Wnt10b deficiency promotes coexpression of myogenic and adipogenic programs in myoblasts. Molecular biology of the cell. . 2005; 16(4): 2039-48.
Lane TF BRCA1 and Transcription. Cancer Biol Ther. 2004; 3(6): 528-33.
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Chang SH, Liu CH, Conway R, Han DK, Nithipatikom K, Trifan OC, Lane TF, Hla T Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proceedings of the National Academy of Sciences of the United States of America. . 2004; 101(2): 591-6.
Doyle SE, O'Connell RM, Miranda GA, Vaidya SA, Chow EK, Liu PT, Suzuki S, Suzuki N, Modlin RL, Yeh WC, Lane TF, Cheng G Toll-like receptors induce a phagocytic gene program through p38. The Journal of experimental medicine. . 2004; 199(1): 81-90.
O'Connell RM, Saha SK, Vaidya SA, Bruhn KW, Miranda GA, Zarnegar B, Perry AK, Nguyen BO, Lane TF, Taniguchi T, Miller JF, Cheng G Type I interferon production enhances susceptibility to Listeria monocytogenes infection. The Journal of experimental medicine. . 2004; 200(4): 437-45.
Krum SA, Miranda GA, Lin C, Lane TF BRCA1 associates with processive RNA polymerase II. The Journal of biological chemistry. . 2003; 278(52): 52012-20.
Krum SA, Womack JE, Lane TF Bovine BRCA1 shows classic responses to genotoxic stress but low in vitro transcriptional activation activity. Oncogene. . 2003; 22(38): 6032-44.
Li G, Robinson GW, Lesche R, Martinez-Diaz H, Jiang Z, Rozengurt N, Wagner KU, Wu DC, Lane TF, Liu X, Hennighausen L, Wu H Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development (Cambridge, England) . 2002; 129(17): 4159-70.
Liu CH, Chang SH, Narko K, Trifan OC, Smith E, Haudenschild C, Lane TF, Hla T Mammary tumorigenesis induced by the overexpression of Cox-2. J. Biol. Chem 2001; 276: 18563-18569.
Lane TF, Collado-Hidalgo A Oncogenes, anti-oncogenes, and genetic regulators of vascular development. Vascular Morphogenesis in the Female Reproductive System 2001; Book Chapter.
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Lane TF, Lin C, Brown MA, Solomon E, Leder P Gene replacement with the human BRCA1 locus: tissue specific expression and rescue of embryonic lethality in mice. Oncogene. . 2000; 19(36): 4085-90.