University of Wisconsin–Madison
College of Agriculture and Life Sciences | School of Medicine and Public Health

Lara Collier

Associate Professor

lcollier@wisc.edu

608-890-2149

4117 Rennebohm Hall

Education
Ph.D., Stanford University (2003), Postdoctoral Research: Largaespada laboratory, University of Minnesota, Twin Cities
Department
Pharmacy
Research Interest
We use genetic and pharmacological approaches in mouse models to study disease etiology and treatment.
Research Fields
Disease Biology, Human, mouse & rat

Research Description:
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.

Representative Publications:
Search PubMed for more publications by Lara Collier

Collier LS*, Carlson CM*, Ravimohan S, Dupuy AJ, Largaespada DA. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature. 2005;436(7048):272-6. *equal contribution

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. A conditional transposon-based insertional mutagenesis screen for hepatocellular carcinoma-associated genes in mice. Nat Biotechnology, 2009 Mar;27(3):264-74.

Starr TK, Allaei R, Silverstein KAT, Staggs RA, Sarver AL, Bergemann TL, Gupta M, O’Sullivan MG, Matise I, Dupuy AJ, Collier LS, Powers S, Oberg AL, Asmann YW, Thibodeau SN, Tessarollo L, Copeland NG, Jenkins NA, Cormier RT, Largaespada DA. A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer. Science, 2009 Mar 27;323(5922):1747-50.

Rahrmann EP*, Collier LS*, Knutson TP, Doyal ME, Kuslak SL, Green LE, Malinowski RL, Roethe L, Akagi K, Waknitz M, Huang W, Largaespada DA, Marker PC Identification of PDE4D as a proliferation promoting factor in prostate cancer using a Sleeping Beauty transposon based somatic mutagenesis screen. Cancer Research, 2009 May 15;69(10):4388-97. *equal contribution

Collier LS, Adams DJ, Hackett CS, Bendzick LE, Akagi K, Davies MN, Diers MD, Rodriguez FJ, Bender AM, Tieu C, Matise I, Dupuy AJ, Copeland NG, Jenkins NA, Hodgson JG, Weiss WA, Jenkins RB, Largaespada DA. Whole-body Sleeping Beauty mutagenesis can cause penetrant leukemia/lymphoma and rare high-grade glioma without associated embryonic lethality. Cancer Res. 2009 Nov 1;69(21):8429-37.

Mattison J, Kool J, Uren A, de Ridder J, Wessels L, Jonkers J, Bignell GR, Butler A, Rust AG, Brosch M, Wilson CH, van der Weyden L, Largaespada DA, Stratton MR, Futreal PA, van Lohuizen M*, Berns A*, Collier LS*, Hubbard T*, Adams DJ*. Novel candidate cancer genes identified by a large-scale cross-species comparative oncogenomics approach. Cancer Res. 2010 Feb 1;70(3):883-95. *equal contribution

Bender AM, Collier LS, Rodriguez FJ, Tieu C, Larson JD, Halder C, Mahlum E, Kollmeyer TM, Akagi K, Sarkar G, Largaespada DA, Jenkins RB. Sleeping Beauty-mediated somatic mutagenesis implicates CSF1 in the formation of high-grade astrocytomas. Cancer Res. 2010 May 1;70(9):3557-65.

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, Taylor MD. Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature. 2012 Feb 15;482(7386):529-33.

Pérez-Mancera PA, Rust AG, van der Weyden L, Kristiansen G, Li A, Sarver AL, Silverstein KAT, 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, ten Hoeve JJ, de Ridder J, Klein AP, Goggins M, Hruban RH, Chang DK, Biankin AV, Grimmond SM, APGI18, Wessels LFA, Wood SA, Iacobuzio-Donahue CA, Pilarsky C,

Largaespada DA, Adams DJ, Tuveson DA. The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature. 2012 Apr 29;486(7402):266-70.

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. A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis. PLOS Genetics. 2012 Nov;8(11):e1003034

Sukup-Jackson MR, Kiraly O, Kay JE, Na L, Rowland EA, Winther KE, Chow DN, Kimoto T, Matsuguchi T, Jonnalagadda VS, Maklakova VI, Singh VR, Wadduwage DN, Rajapakse J, So PTC, Collier LS and Engelward BP. ROSA26-GFP direct repeat (RaDR-GFP) mice reveal tissue- and age-dependence of homologous recombination in mammals in vivo. PLoS Genet. 2014 Jun 5;10(6):e1004299

Vyazunova I, Maklakova VI, Berman S, De I, Steffen MD, Hong W, Lincoln H, Morrissy AS, Taylor MD, Akagi K, Brennan CW, Rodriguez FJ and Collier LS. Sleeping Beauty mouse models identify candidate genes involved in gliomagenesis. PLoS One. 2014 Nov 25;9(11):e113489.

De I, Nikodemova M, Steffan MD, Sokn E, Watters JJ and Collier LS. Csf1 over-expression has pleiotropic effects on microglia in vivo. Glia. 2014 Dec;62(12):1955-67

Nikodemova M, Kimyon R, De I, Small A, Collier LS and Watters JJ. Microglial numbers attain adult levels after undergoing a rapid decrease in cell number in the third postnatal week. J Neuroimmunol. 2015 Jan 15;278:280-8

Morrissy AS, Garzia L, Shih D, Zuyderduyn S, Huang X, Skowron P, Remke M, Cavalli F, Ramaswamy V, Lindsay P, Jelveh S, Donovan L, Wang X, Luu B, Zayne K, Li Y, Mungall K, Mayoh C, Thiessen N, Mercier E, Ma Y, Tse K, Zeng T, Shumansky K, Roth A, Shah S, Farooq H, Kijima N, Holgado BL, Lee J, Matan-Lithwick S, Qin L, Reimand J, Rolider A, Liu J, Thompson Y, Wu X, Mack S, Manno A, Michealraj KA, Nor C, Peacock J, Pugh T, Ally A, Bilenky M, Butterfield Y, Carlsen R, Cheng Y, Li H, Long W, Mayo M, Plettner P, Qian J, Schein J, Tam A, Wong T, Birol I, Zhao Y, Chuah E, Corbett R, Dhalla N, He A, Lee D, Faria C, Pimentel J, Nunes S, Shalaby T, Grotzer M, Pollack I, Hamilton R, Li X-N, Bendel A, Fults D, Walter A, Kumabe T, Tominaga T, Collins VP, Cho Y-J, Hoffman C, Lyden D, Wisoff J, Garvin Jr. J, Stearns D, Massimi L, Schüller U, Sterba J, Zitterbart K, Puget S, Ayrault O, Dunn S, Tirapelli D, Carlotti C, Wheeler H, Hallahan A, Ingram W, MacDonald T, Olson J, Van Meir E, Lee J-Y, Wang K-C, Kim S-K, Cho B-K, Pietsch T, Fleischhack G, Tippelt T, Ra YS, Bailey S, Clifford S, Lindsey J, Eberhart C, Cooper M, Packer R, Massimino M, Garre ML, Bartels U, Tabori U, Hawkins C, Dirks P, Rutka J, Bouffet E, Wechsler-Reya R, Weiss W, Collier LS, Dupuy A, Korshunov A, Jones D, Kool M, Northcott P, Pfister A, Largaespada DA, Mungall A, Moore R, Jabado N, Bader G, Jones S, Malkin D, Marra M and Taylor MD. Divergent Clonal Selection Dominates Medulloblastoma at Recurrence. Nature. 2016 Jan 21;529(7586):351-7.

De I, Steffen M, Clark PA, Patros CJ, Sokn E, Bishop SM, Litscher S, Maklakova VI, Kuo JS, Rodriguez FJ and Collier LS. CSF1 overexpression promotes high-grade glioma formation in vivo without impacting the polarization status of glioma-associated microglia and macrophages. Cancer Res. 2016 May 1;76(9):2552-60.