Faculty: Lara Collier
|Dept:||Assistant Professor, School of Pharmacy, Pharmaceutical Sciences Division|
|Contact:|| 4117 Rennebohm (School of Pharmacy)|
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
- American Cancer Society Research Scholar Grant
- Kimmel Scholar
- Howard Temin K01 Award from the NCI
- American Cancer Society Post Doctoral Fellowship
- 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 glioma models identify candidate glioma genes. Under revision.
- De I, Nikodemova M, Steffen MD, Sokn E, Maklakova VI, Watters JJ and Collier LS. CSF1 over-expression has pleiotropic effects on microglia in vivo. In press at Glia.
- Sukup-Jackson MR, Kiraly O, 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.
- 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.
- 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, 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, 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.