Andriy Marusyk, PhD
Tumors are mini eco-systems, where evolving populations of genetically and phenotypically heterogeneous malignant cells are engaged in a network of reciprocal interactions with multiple normal cell types as well as with non-cellular components of tumor micro and macro environment. Research over recent decades shed light on molecular pathways essential for cancer cell survival, leading to development of multiple novel therapeutic approaches. Unfortunately, almost in all cases anti-cancers therapies provide only a temporary success, as tumors eventually relapse owing to outgrowth of therapy-resistant phenotypes. Preventing and limiting this outgrowth cannot be achieved only by focusing on proximal molecular mechanisms of resistance. We also need to develop adequate level of understanding of evolutionary dynamics, a knowledge that is mostly lacking. The main focus of research in my lab is filling this gap through development of experimental models that allow characterization and quantification of dynamics of populations of cancers cells under base-like conditions as well as under the stress of anti-cancer therapies. Another major research effort is centered on characterization of interactions between malignant cells and tumor associated fibroblasts with the aim of developing means to overcome stromal resistance to anti-cancer therapies.
Education And Training
- Taras Shevchenko National University, MS - Biology, Cell Biology and Genetic Engineering
- University of Colorado , PhD - Biophysics and Molecular Genetics
- University of Colorado Health Sciences Center, Postdoctoral Fellow
- , Postdoctoral Felllow - Dana Farber Cancer Institute & Harvard Medical School
- Marusyk A, Tabassum D, Janiszewska M, Place A, Trinh A, Rozhok AI, Pyne S, Guerriero J, Shu S, Ekram M, Ishkin A, Cahill DP, Nikolsky Y, Chan TA, Rimawi MF, Hilsenbeck SG, Schiff R, Osborne CK, Letai A, Polyak K. Spatial Proximity to Fibroblasts Impacts Molecular Features and Therapeutic Sensitivity of Breast Cancer Cells Influencing Clinical Outcomes. Cancer Res. 2016 Nov;76(22):6495-6506. Pubmedid: 27671678.
- Su Y, Subedee A, Bloushtain-Qimron N, Savova V, Krzystanek M, Li L, Marusyk A, Tabassum DP, Zak A, Flacker MJ, Li M, Lin JJ, Sukumar S, Suzuki H, Long H, Szallasi Z, Gimelbrant A, Maruyama R, Polyak K. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer. Cell Rep. 2015 Jun;11(10):1549-1563. Pubmedid: 26051943.
- Marusyk A, Tabassum DP, Altrock PM, Almendro V, Michor F, Polyak K. Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity. Nature. 2014 Oct;514(7520):54-58. Pubmedid: 25079331. Pmcid: PMC4184961.
- Almendro V, Cheng YK, Randles A, Itzkovitz S, Marusyk A, Ametller E, Gonzalez-Farre X, Muñoz M, Russnes HG, Helland A, Rye IH, Borresen-Dale AL, Maruyama R, van Oudenaarden A, Dowsett M, Jones RL, Reis-Filho J, Gascon P, Gönen M, Michor F, Polyak K. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Rep. 2014 Feb;6(3):514-527. Pubmedid: 24462293. Pmcid: PMC3928845.
- Chin YR, Yoshida T, Marusyk A, Beck AH, Polyak K, Toker A. Targeting Akt3 signaling in triple-negative breast cancer. Cancer Res. 2014 Feb;74(3):964-973. Pubmedid: 24335962. Pmcid: PMC3946502.
- Cuiffo BG, Campagne A, Bell GW, Lembo A, Orso F, Lien EC, Bhasin MK, Raimo M, Hanson SE, Marusyk A, El-Ashry D, Hematti P, Polyak K, Mechta-Grigoriou F, Mariani O, Volinia S, Vincent-Salomon A, Taverna D, Karnoub AE. MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis. Cell Stem Cell. 2014 Dec;15(6):762-774. Pubmedid: 25515522.
- Marusyk A, Almendro V, Polyak K. Intra-tumour heterogeneity: a looking glass for cancer?. Nat Rev Cancer. 2012 May;12(5):323-334. Pubmedid: 22513401.
- Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, Bloushtain-Qimron N, Kim JJ, Choudhury SA, Maruyama R, Wu Z, Gönen M, Mulvey LA, Bessarabova MO, Huh SJ, Silver SJ, Kim SY, Park SY, Lee HE, Anderson KS, Richardson AL, Nikolskaya T, Nikolsky Y, Liu XS, Root DE, Hahn WC, Frank DA, Polyak K. The JAK2/STAT3 signaling pathway is required for growth of CD44⁺CD24⁻ stem cell-like breast cancer cells in human tumors. J Clin Invest. 2011 Jul;121(7):2723-2735. Pubmedid: 21633165. Pmcid: PMC3223826.
- Lyons TR, O'Brien J, Borges VF, Conklin MW, Keely PJ, Eliceiri KW, Marusyk A, Tan AC, Schedin P. Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2. Nat Med. 2011 Aug;17(9):1109-1115. Pubmedid: 21822285. Pmcid: PMC3888478.
- Marusyk A, Porter CC, Zaberezhnyy V, DeGregori J. Irradiation selects for p53-deficient hematopoietic progenitors. PLoS Biol. 2010 Mar;8(3):e1000324. Pubmedid: 20208998. Pmcid: PMC2830447.
- Henry CJ, Marusyk A, Zaberezhnyy V, Adane B, DeGregori J. Declining lymphoid progenitor fitness promotes aging-associated leukemogenesis. Proc Natl Acad Sci U S A. 2010 Dec;107(50):21713-21718. Pubmedid: 21098275. Pmcid: PMC3003039.
- Marusyk A, Casás-Selves M, Henry CJ, Zaberezhnyy V, Klawitter J, Christians U, DeGregori J. Irradiation alters selection for oncogenic mutations in hematopoietic progenitors. Cancer Res. 2009 Sep;69(18):7262-7269. Pubmedid: 19738065. Pmcid: PMC2745506.
- Marusyk A, DeGregori J. Declining cellular fitness with age promotes cancer initiation by selecting for adaptive oncogenic mutations. Biochim Biophys Acta. 2008 Jan;1785(1):1-11. Pubmedid: 17980163. Pmcid: PMC2234267.
- Marusyk A, Wheeler LJ, Mathews CK, DeGregori J. p53 mediates senescence-like arrest induced by chronic replicational stress. Mol Cell Biol. 2007 Aug;27(15):5336-5351. Pubmedid: 17515610. Pmcid: PMC1952086.