University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Luika Timmerman, PhD

Luika Timmerman, PhD

Assistant Research Molecular Biologist and Independent Investigator, UCSF Helen Diller Family Comprehensive Center

Cancer Center Program Memberships

Breast Oncology

Research Summary

My laboratory is engaged in identifying novel cancer therapeutic targets that impact tumor-specific metabolic functions. This work grows from the analysis of expression data derived from a panel of 50 breast cancer-derived cell lines and non-tumorigenic breast epithelial derivatives. The astonishing differences in metabolic gene expression levels, and the paucity of current therapeutics that target any of these processes compelled me to explore these differences in terms of novel therapeutic development. My laboratory routinely uses cell line panels and PDX derived tumors in direct experimental tests of hypotheses derived from expression data and from the literature. Although slow, hypothesis testing using multiple, independently-derived lines allows us to understand the prevalence of various responses- and allows us to pay less attention to rare responses that may not translate to the majority of tumors seen in the clinic. Gene products and metabolic activities that we are currently targeting have also been validated using a large variety of publically-available primary expression datasets and from within the UCSF community.

Our current studies focus on xCT (SLC7A11), the cystine:glutamate exchanger involved in cellular reactive oxygen species control and chemotherapeutic inactivation. xCT is over-expressed by the poor prognosis subset of most solid tumor types and their culture-adapted derivatives. xCT activity is required for cell proliferation and/or viability, is expressed by few other cells in the body, and xCT knockout mice are viable, healthy, and fertile; making xCT an ideal cancer therapeutic target. While most of our past work on xCT has focused on triple negative breast tumors, we recently found that xCT is highly expressed by the majority of lung tumors- an extremely large patient population with few good therapeutic options and terrible survival statistics. We are working to identify clinically useful biomarkers of xCT inhibition sensitivity, and, via phage display technology, have produced preliminary nanobody-based reagents that both specifically identify xCT and partially block xCT function. These nanobodies will be further refined for use as clinically-approved xCT-detection and therapeutic reagents for many types of solid tumors, particularly triple negative breast tumors. Our bioinformatics-based search for xCT expression patterns in primary tumor samples led to the startling realization that few if any genomics-era analyses of drug resistance development or of drug resistant primary tumor samples have been conducted. Filling this fundamental gap in our understanding of cancer is our future goal, and will also lead to a clearer understanding of the role of xCT and metabolic alterations in tumor development, progression, and therapeutic resistance.

Education

Stanford University, Stanford California, MS, 1987, Biology
Stanford University, Stanford California, PhD, 1999, Immunology
University of California at San Francisco, Postdoctoral Research, 2000-2003, Cancer Biology

 

Professional Experience

  • 1988-1990
    Research Technician, with Prof. Hugh McDevitt, Stanford University
  • 1990-1999
    Graduate Research/Teaching Assistant with Prof. Gerald Crabtree, Stanford University
  • 2000-2002
    Carol Frank Buck Plummer Fellowship, UCSF/Diller Family Comprehensive Cancer Center.
  • 2000-2003
    Postdoctoral Research Fellow, UCSF/Diller Family Comprehensive Cancer Center, with Dr. Frank McCormick
  • 2004-present
    Assistant Research Molecular Biologist and Independent Investigator, UCSF/Diller Family Comprehensive Center

Selected Publications

  1. Cobler L, Zhang H, Suri P, Park C, Timmerman LA. xCT inhibition sensitizes tumors to ?-radiation via glutathione reduction. Oncotarget. 2018 Aug 17; 9(64):32280-32297.
    View on PubMed
  2. Padró M, Louie RJ, Lananna BV, Krieg AJ, Timmerman LA, Chan DA. Genome-independent hypoxic repression of estrogen receptor alpha in breast cancer cells. BMC Cancer. 2017 03 20; 17(1):203.
    View on PubMed
  3. Timmerman LA, Holton T, Yuneva M, Louie RJ, Padró M, Daemen A, Hu M, Chan DA, Ethier SP, van 't Veer LJ, Polyak K, McCormick F, Gray JW. Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell. 2013 Oct 14; 24(4):450-65.
    View on PubMed
  4. Kuemmerle NB, Rysman E, Lombardo PS, Flanagan AJ, Lipe BC, Wells WA, Pettus JR, Froehlich HM, Memoli VA, Morganelli PM, Swinnen JV, Timmerman LA, Chaychi L, Fricano CJ, Eisenberg BL, Coleman WB, Kinlaw WB. Lipoprotein lipase links dietary fat to solid tumor cell proliferation. Mol Cancer Ther. 2011 Mar; 10(3):427-36.
    View on PubMed
  5. Oda K, Okada J, Timmerman L, Rodriguez-Viciana P, Stokoe D, Shoji K, Taketani Y, Kuramoto H, Knight ZA, Shokat KM, McCormick F. PIK3CA cooperates with other phosphatidylinositol 3'-kinase pathway mutations to effect oncogenic transformation. Cancer Res. 2008 Oct 01; 68(19):8127-36.
    View on PubMed
  6. Grego-Bessa J, Díez J, Timmerman L, de la Pompa JL. Notch and epithelial-mesenchyme transition in development and tumor progression: another turn of the screw. Cell Cycle. 2004 Jun; 3(6):718-21.
    View on PubMed
  7. Maldonado JL, Timmerman L, Fridlyand J, Bastian BC. Mechanisms of cell-cycle arrest in Spitz nevi with constitutive activation of the MAP-kinase pathway. Am J Pathol. 2004 May; 164(5):1783-7.
    View on PubMed
  8. Timmerman LA, Grego-Bessa J, Raya A, Bertrán E, Pérez-Pomares JM, Díez J, Aranda S, Palomo S, McCormick F, Izpisúa-Belmonte JC, de la Pompa JL. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 2004 Jan 01; 18(1):99-115.
    View on PubMed

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