Lara Collier
Assistant Professor
Ph.D., Stanford University, 2003
Postdoctoral Research: Largaespada laboratory, University of Minnesota, Twin Cities
Address: 4117 Rennebohm Hall
Telephone: 890-2149
E-mail: lcollier@wisc.edu
Research Interests:
Cancer genetics
Research Fields:
Genomics
Human and Mammalian
Cancer Genetics
Mouse Genetics
Research Description: Research in the Collier laboratory focuses on using forward genetic approaches to understanding the molecular basis of cancer initiation, progression and therapy resistance. We use the Sleeping Beauty (SB) transposon system as an insertional mutagen for cancer gene discovery in mouse models of human cancer. We have generated mice that suffer transposon mutagenesis in essentially all cells of the body. Most of these mice develop leukemia due to insertional mutagenesis of cancer genes in the hematopoietic system, but gliomas also occur at low penetrance. In addition to frank tumors, we have also observed hyperproliferative lesions in the prostate glands of these mice. We have used these tumors to identify new candidate cancer genes. In leukemia, we have identified a poorly studied kinase as a candidate tumor suppressor gene. We hypothesize that it functions during mitosis to prevent improper segregation of chromosomes to daughter cells, and are therefore investigating if it modulates the response of leukemia cells to chemotherapeutic agents that act as mitotic poisons. We have also identified a signaling molecule as a candidate glioma oncogene. We are pursuing genetic studies in mice to determine if this gene is necessary or sufficient for glioma formation in vivo. We hypothesize that these studies will determine if inhibitors that target this signaling pathway should be investigated as therapies for human glioma. We are working to generate a glioma specific SB model for use in future genetic and pre-clinical studies. The SB system is also being used to study the genetic basis of therapy resistance in both gliomas and prostate cancer using cell culture and animal models. In addition to using the SB system for cancer gene identification, the laboratory is also studying a novel mouse model for leukemia that we discovered and named Spontaneous dominant leukemia (Sdl). We are using the Sdl model to study the molecular events driving tumor initiation and progression and are taking a positional cloning approach to identify the affected gene. We hypothesize that the mutant gene in Sdl mice will also function as a tumor suppressor gene or oncogene in human leukemia. Future avenues of study in the laboratory also include continued analysis of SB-induced tumors, research on the function of additional candidate cancer genes we identify using SB and determining if these genes have a role in tumor formation in humans.
Representative Publications:
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 July 14, 436(7048):272-6. (see comment in: Nature, 2005 July 14, 436(7048):184-6.) * 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. PMC2712727
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. PMC2743559
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 NIHMS111605
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. NIHMS144184
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. *co-senior authors PMC2880710
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. PMC2862088
Assistant Professor
Ph.D., Stanford University, 2003
Postdoctoral Research: Largaespada laboratory, University of Minnesota, Twin Cities
Address: 4117 Rennebohm Hall
Telephone: 890-2149
E-mail: lcollier@wisc.edu
Research Interests:
Cancer genetics
Research Fields:
Genomics
Human and Mammalian
Cancer Genetics
Mouse Genetics
Research in the Collier laboratory focuses on using forward genetic approaches to understanding the molecular basis of cancer initiation, progression and therapy resistance. We use the Sleeping Beauty (SB) transposon system as an insertional mutagen for cancer gene discovery in mouse models of human cancer. We have generated mice that suffer transposon mutagenesis in essentially all cells of the body. Most of these mice develop leukemia due to insertional mutagenesis of cancer genes in the hematopoietic system, but gliomas also occur at low penetrance. In addition to frank tumors, we have also observed hyperproliferative lesions in the prostate glands of these mice. We have used these tumors to identify new candidate cancer genes. In leukemia, we have identified a poorly studied kinase as a candidate tumor suppressor gene. We hypothesize that it functions during mitosis to prevent improper segregation of chromosomes to daughter cells, and are therefore investigating if it modulates the response of leukemia cells to chemotherapeutic agents that act as mitotic poisons. We have also identified a signaling molecule as a candidate glioma oncogene. We are pursuing genetic studies in mice to determine if this gene is necessary or sufficient for glioma formation in vivo. We hypothesize that these studies will determine if inhibitors that target this signaling pathway should be investigated as therapies for human glioma. We are working to generate a glioma specific SB model for use in future genetic and pre-clinical studies. The SB system is also being used to study the genetic basis of therapy resistance in both gliomas and prostate cancer using cell culture and animal models. In addition to using the SB system for cancer gene identification, the laboratory is also studying a novel mouse model for leukemia that we discovered and named Spontaneous dominant leukemia (Sdl). We are using the Sdl model to study the molecular events driving tumor initiation and progression and are taking a positional cloning approach to identify the affected gene. We hypothesize that the mutant gene in Sdl mice will also function as a tumor suppressor gene or oncogene in human leukemia. Future avenues of study in the laboratory also include continued analysis of SB-induced tumors, research on the function of additional candidate cancer genes we identify using SB and determining if these genes have a role in tumor formation in humans.
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 July 14, 436(7048):272-6. (see comment in: Nature, 2005 July 14, 436(7048):184-6.) * 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. PMC2712727
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. PMC2743559
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 NIHMS111605
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. NIHMS144184
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. *co-senior authors PMC2880710
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. PMC2862088
