Faculty: Lara Collier
|Dept:||Assistant Professor, Pharmacy|
|Contact:|| 4117 Rennebohm |
Research in the Collier laboratory utilizes mouse models to study molecular drivers of tumorigenesis and the impact of new drugs involved in cancer diagnosis or therapy. Through studying a spontaneous mouse model of leukemia, we have discovered an allele of Mcm4 that acts in a dominant manner to promote genomic instability and tumorigenesis. Mcm4 functions during DNA replication and we are now using this model to study how replicative stress promotes genomic instability, and are using transposon mutagenesis to discover processes that cooperate with replication stress to promote tumorigenesis. In a separate study, we used transposon mutagenesis in mice to identify Csf1 (Macrophage colony stimulating factor 1) as a candidate glioma oncogene. Through transgenic models we have shown that Csf1 overexpression in the brain dramatically increases microglial numbers and accelerates gliomagenesis in a transgenic glioma model. We are now studying the mechanisms by which Csf1 increases microglial numbers and impacts microglial phenotypes. In addition to mechanistic studies we are utilizing our mouse cancer models for pre-clinical testing of novel imaging agents and targeted therapies. We are using our leukemia models to test if a novel imaging/therapeutic agent has efficacy in diagnosing and treating hematologic cancers. We are using our Csf1 and glioma models to test the impact of a small molecule inhibitor of the CSF1 receptor on microglial phenotypes and glioma development. As high levels of Csf1 are found in multiple CNS diseases, the results of this study may have therapeutic implications in many CNS pathologies.
Honors & Awards
- 2008: Robinson Travel Award (to attend “The Society for Neuro-Oncology annual scientific meeting”)
- 2006 - present: K01 Howard Temin award from the NCI
- PLoS Genet. 2014 Jun 5;10(6):e1004299. doi: 10.1371/journal.pgen.1004299
- Bagley BN, Keane TM, Maklakova VI, Marshall JG, Lester RA, Cancel MM, Paulsen AR, Bendzick LE, Been RA, Kogan SC, Cormier RT, Kendziorski C, Adams DJ, and Collier LS. (2012). A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis. PLoS Genet. 8 Epub 2012 Nov 1. PMID: 23133403
- Pérez-Mancera PA, Rust AG, van der Weyden L, Kristiansen G, Li A, Sarver AL, Silverstein KA, Grützmann R, Aust D, Rümmele P, Knösel T, Herd C, Stemple DL, Kettleborough R, Brosnan JA, Li A, Morgan R, Knight S, Yu J, Stegeman S, Collier LS, Wessels LF, Wood SA, Iacobuzio-Donahue CA, Pilarsky C, Largaespada DA, Adams DJ, and Tuveson DA. (20!2). The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature. 486:266-70. Erratum in: Nature. 2013 Feb 21;494(7437):390. Scarlett, Christopher J [added]; Kaplan, Warren [added]; Scarpa, Aldo [added], Das, Amithabad [corrected to Das, Amitabha]. PMID: 22699621
- Bergerson RJ, Collier LS, Sarver AL, Been RA, Lugthart S, Diers MD, Zuber J, Rappaport AR, Nixon MJ, Silverstein KA, Fan D, Lamblin AF, Wolff L, Kersey JH, Delwel R, Lowe SW, O'Sullivan MG, Kogan SC, Adams DJ, and Largaespada DA. (2012). An insertional mutagenesis screen identifies genes that cooperate with Mll-AF9 in a murine leukemogenesis model. Blood. 119:4512-23. Epub 2012 Mar 16. PMID: 22427200
- Wu X, Northcott PA, Dubuc A, Dupuy AJ, Shih DJ, Witt H, Croul S, Bouffet E, Fults DW, Eberhart CG, Garzia L, Van Meter T, Zagzag D, Jabado N, Schwartzentruber J, Majewski J, Scheetz TE, Pfister SM, Korshunov A, Li XN, Scherer SW, Cho YJ, Akagi K, MacDonald TJ, Koster J, McCabe MG, Sarver AL, Collins VP, Weiss WA, Largaespada DA, Collier LS, and Taylor MD. (2012). Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature ;482:529-33. PMID 22343890
- Bender AM, Collier LS, Rodriguez FJ, Tieu C, Larson JD, Halder C, Mahlum E, Kollmeyer TM, Akagi K, Sarkar G, Largaespada DA, and Jenkins RB (2010). Sleeping beauty-mediated somatic mutagenesis implicates CSF1 in the formation of high-grade astrocytomas. Cancer Res. 70:3557-65. PMID: 20388773
- Keng VW, Villanueva A, Chiang DY, Dupuy AJ, Ryan BJ, Matise I, Silverstein KAT, Sarver S, Starr TK, Akagi K, Tessarollo L, Collier LS, Powers S, Lowe SW, Jenkins NA, Copeland NG, Llovet JM, and Largaespada DA. (2009). A conditional transposon-based insertional mutagenesis screen for hepatocellular carcinoma-associated genes in mice. In press at Nature Biotechnology.
- Thielen JL, Volzing KG, Collier LS, Green LE, Largaespada DA, and Marker PC. (2007). Markers of prostate region-specific epithelial identity define anatomical locations in the mouse prostate that are molecularly similar to human prostate cancers. Differentiation. 75:49-61.
- Geurts AM, Collier LS, Geurts JL, Oseth LL, Bell ML, Mu D, Lucito R, Godbout SA, Green LE, Lowe SW, Hirsch BA, Leinwand LA, and Largaespada DA. (2006). Gene mutations and genomic rearrangements in the mouse as a result of transposon mobilization from chromosomal concatemers. PloS Genetics. 29:2
- Geurts AM, Hackett CS, Bell JB, Bergemann TL, Collier LS, Carlson CM, Largaespada DA, and Hackett PB. (2006). Structure-based prediction of insertion-site preferences of transposons into chromosomes. Nucleic Acids Res. 34:2803-2811.
Invited Review Articles and Book Chapters
- Largaespada DA and Collier LS. (2008). Identification of transposon-genomic DNA junctions. Methods Mol Biol. 435:95-108.
- Collier LS and Largaespada DA. (2007). Transposable elements and the dynamic somatic genome. Genome Biology. 8:S5.
- Collier LS and Largaesapda DA. (2007). Transposons for somatic mutagenesis: Sleeping Beauty and beyond. Genome Biology. 8:S15.
- Collier LS and Largaespada DA. (2006). Transforming science: cancer gene identification. Curr Opin Genet Dev. 16:23-9.
- Collier LS and Largaespada DA. (2005). Hopping around the tumor genome: transposons for cancer gene discovery.Cancer Res. 65:9607-10.
- Member, The Society for Neuro-Oncology.
- Attended “ENDO08” meeting, June 2008, San Francisco, CA.