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Experimental Oncology

Lynne-Marie Postovit

Associate Professor, Sawin-Baldwin Chair in Ovarian Cancer & Dr. Anthony Noujaim Legacy Oncology Chair Canadian Institutes of Health Research Premier New Investigator (2009)

Experimental Oncology
Department of Oncology
University of Alberta
5-142E Katz Group Building
114th St and 87th Ave
Edmonton, AB, T6G 2E1

Tel: 780.492.6342
postovit@ualberta.ca

Profile

Research Interests:

Bidirectional communication between cells and their microenvironment is a hallmark of both cancer progression and embryological development. Indeed, in all physiological instances, cells do not survive autonomously, but rather rely on extracellular cues to direct functions as diverse as proliferation, apoptosis, invasion and differentiation. The past decade has seen an explosion of research on cells with the capacity to differentiate in response to specific microenvironmental cues. During embryogenesis, these "stem cells" are the source of all cell lineages and in adulthood they function in tissue repair and rejuvenation. Recent studies have found that cancers may similarly develop from stem cell populations, and that these rarely occurring cells care likely responsible for tumour formation, drug resistance and metastasis. The unifying goal of our research program is to determine what types of microenvironments regulate normal and cancer stem cell plasticity and function, and to elucidate the mechanisms by which such microenvironments elicit their effects. Put in another way, we are interested in epigenetics; or how the microenvironment can regulate cell function by changing which genes can be expressed.  Ultimately, these studies will lead to the development of methods to maintain normal stem cell pluripotency and to inhibit cancer cell plasticity and metastasis. This research program is comprised of the following projects: 
 
  • Role of oxygen as an epigenetic regulator of tumour progression and metastasis
  • Role of the extracellular matrix proteins in the regulation of stem cells and cancers
  • Function and regulation of  the embryonic protein Nodal in cancer and stem cells
  • Microenvironmental regulation of cancer progression at the cancer-stroma interface.
  • Microenvironmental regulation of placental development at the feto-maternal interface
  • Identifying biomarkers that can predict ovarian cancer
  • Identifying targets for the treatment and prevention of ovarian cancer metastasis
     
Translational Research Team Focussed of Cancers Affecting Women
 
One of our major goals is to see the work that we do in the lab translate into new treatments or early detection methods for cancer patients:  We want to translate our scientific results into clinical practice.  To do this, we work in teams.  One newly formed team at the University of Alberta, is the Ovarian Cancer Research Team.  Faculty members in this team include Dr. Helen Steed (surgical oncology), Dr. YangXin Fu (experimental oncology) and Dr. Cheng-Han Lee (pathology).   Together with scientists and clinicians in our research programs, we will work together to discover new targets for the treatment and earlier detection of ovarian cancer.  This will complement ongoing projects that the Postovit lab has in the area of breast cancer.  A great deal of infrastructure, such as tumour banks and a state-of-the-art pathology suite, help aid our translational studies.  Moreover, we will be establishing a pre-clinical animal core.  This will include animals containing patient derived xenografts (PDX).  Importantly, the PDX models will allow our group to test drug combinations on heterogeneous tumours in a manner that is more clinically relevant than clonally derived conventional xenograft models.   

Publications

Publications (Last 5 years and other key contributions) (Lab members are underlined)

Das P, Siegers GM and Postovit LM.  (2013) Illuminating luminal B: QSOX1 as a subtype-specific biomarker.  Breast Cancer Research. 15(3):104.
 
Quail DF, Siegers GM, Jewer M and Postovit LM.  (2013) Nodal in Embryogenesis and Tumourigenesis.  International Journal of Biochemistry and Cell Biology.  45(4):885-98.
 
Quail DF, Zhang G, Findlay SD, Hess DA and Postovit LM.  (2013)  Nodal promotes invasive phenotypes via a Mitogen Activated Protein Kinase-dependent pathway.  Oncogene. EPub.
 
Quail DF, Zhang G, Walsh L, Siegers GM, Dieters-Castator D, Findlay SD, Putman D, Hess DA and Postovit LM.  (2012) The embryonic protein Nodal promotes breast cancer tumorigenesis.  PLoS ONE.  7(11):e48237.
 
Hughes CS, Radan L, Betts D, Postovit LM and Lajoie GA.  (2012) Mass Spectrometry-Based Proteomics Analysis of the Matrix Microenvironment in Pluripotent Stem Cell Culture.  Molecular and Cellular Proteomics. 11(12):1924-36. 
 
Jewer M, Findlay SD and Postovit LM.  (2012)  Post-transcriptional regulation in cancer progression:  Alternative splicing and translational control promote developmental phenotypes.  Journal of Cell Communication and Signaling.  DOI 10.1007/s12079-012-0179-x.
 
Quail DF, Zhang G, Walsh L, Findlay SD, Fung L, Ablack A, Moreno J, Lewis J, Done SJ, Hess DA and Postovit LM.  (2012)  The embryonic protein Nodal promotes breast cancer vascularization Cancer Research. 72(15):3851-63.
 
Quail DF, Maciel TJ, Rogers K and Postovit LM.  (2012)  A unique 3D in vitro cellular invasion assay.  Journal of Biomolecular Screening.  17(8):1088-95.
 
Quail DF, Taylor MJ, and Postovit LM.  (2012)  Microenvironmental regulation of cancer stem cell phenotypes.  Current Stem Cell Research & Therapy.  7(3):197-216.
 
Quail DF, Taylor M, Walsh L, Dieters-Castator D, Das P, Jewer M, Zhang G and Postovit LM. (2011) Low oxygen levels induce the expression of the embryonic morphogen Nodal.  Molecular Biology of the Cell: 22(24):4809-21.
 
Hughes CS, Radan L, Betts D, Postovit LM and Lajoie GA. (2011) Proteomic analysis of extracellular matrices used in human embryonic stem cell culture. Proteomics:  11(20):3983-91.
 
Medeiros PJ, Al-Khazraji BK, Novielli NM, Postovit LM, Chambers AF and Jackson DN. (2011) Neuropeptide Y stimulates proliferation and migration in the 4T1 breast cancer cell line. International Journal of Cancer: 131(2):276-86.
 
Zajac M, Law J, Pampillo M, Cvetkovic DD, McColl L, Pape C, Di Guglielmo GM, Postovit LM, Babwah AV and Bhattacharya M. (2011) GPR54 (KISS1R) transactivates EGFR to promote breast cancer cell invasiveness. PLoS ONE: 6(6):e21599.
 
Lawrence MG, Margaryan NV, Loessner D, Collins A, Kerr KM, Turner M, Seftor EA, Stephens CR, Lai J, APC BioResource, Postovit LM, Clements JA and Hendrix MJ.  (2011)  Reactivation of embryonic nodal signaling is associated with tumor progression and promotes the growth of prostate cancer cells.  Prostate: 71(11):1198-209.
 
Hughes CS, Nuhn A,  Postovit LM and Lajoie GA.  (2011)  Proteomics of Human Embryonic Stem Cells. Proteomics: 11(4):675-90.
 
Hardy KM, Kirschmann DA, Seftor EA, Margaryan NV, Postovit LM, Strizzi L and Hendrix MJ.  (2010)  Regulation of Nodal expression by Notch4 facilitates the aggressive melanoma phenotype. Cancer Research:  70(24):10340-50.  Cover Illustration.
 
Hughes CS, Postovit LM, and Lajoie GA.   Matrigel: A Complex Protein Mixture Required for Optimal Growth of Cell Culture. (2010)  Proteomics: 10(9):1886-90.
 
Zhang J, Postovit LM, Wang D, Gardiner RB, Harris R, Abdul MM, and Thomas AA. In situ loading of basic Fibroblast Growth Factor (bFGF) within porous silica nanoparticles for a prolonged release. (2009) Nanoscale Research Letter: 4(11):1297-1302.
 
Li TT, Alemayehu M, Aziziyeh A, Pape C, Pampillo M, Postovit LM, Mills GB, Babwah AV, and Bhattacharya M.  (2009). Β-arrestin/ral signaling regulates lysophosphatidic acid-mediated migration and invasion of human breast tumor cells.  Molecular Cancer Research: 7(7):1064-77.  Cover Illustration.
 
Galat V, Binas B, Iannaccone S, Postovit LM, Bisrat D, and Iannaccone P.  (2009). Developmental potential of rat extraembryonic stem cells.  Stem Cells and Development:  Nov;18(9):1309-18. 
 
Strizzi L, Hardy KM, Seftor EA, Costa FF, Kirschmann DA, Seftor REB, Postovit LM, and Hendrix MJC.  (2009). Development and cancer:  At the crossroads of Nodal and Notch signalling.  Cancer Research. 69(18):OF1–4.
 
Strizzi L, Postovit LM, Margaryan NV, Lipavsky A, Gadiot J, Blank C, Seftor REB, Seftor EA, and Hendrix MJC.  (2009)  Nodal as a biomarker for melanoma progression and a new therapeutic target for clinical intervention.  Expert Review Dermatology:  4(1):67-78.
 
Kasemeier-Kulesa JC, Teddy JM, Postovit LM, Seftor EA, Seftor RE, Hendrix MJ, and Kulesa PM.  (2008)  Reprogramming multipotent tumor cells with the embryonic neural crest microenvironment. Developmental Dynamics:  237(10):2657-66.
 
Postovit LM, Margaryan NV, Seftor REB, Seftor EA, Wheaton WW, Kirschmann DA, Abbott DA, and Hendrix MJC. (2008) Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells.  Proceedings of the National Academy of Science USA:  105(11):4329-34.
 
Postovit LM, Abbott D, Payne SP, Wheaton WW, Margaryan NV, Amir S, Sullivan R, Innsen M, Csiszar K, Hendrix MJC, and Kirschmann DA.  (2008)  Hypoxia-reoxygenation:  a dynamic regulator of lysyl oxidase facilitated breast cancer migration.  Journal of Cellular Biochemistry:  103(5):1369-78.
 
Hendrix MJC, Seftor EA, Seftor REB, Kaseemeier-Kulesa J, Kulesa PM, and Postovit LM.  (2007)  Reprogramming metastatic tumour cells with embryonic microenvironments. Nature Reviews Cancer:  7(4):246-55.  Cover Illustration.
 
Postovit LM, Seftor EA, Seftor REB, and Hendrix MJC.  (2007). Targeting Nodal in malignant melanoma cells.  Expert Opinion on Therapeutic Targets:  11(4):497-505.
 
Postovit LM, Costa FF, Bischof JM, Seftor EA, Wen B, Seftor REB, Feinberg AP, Soares MB, and Hendrix MJC.  (2006) The commonality of plasticity underlying multipotent tumor cells and embryonic stem cells.  Journal of Cellular Biochemistry:  101(4):908-17.
 
Postovit LM, Seftor EA, Seftor REB, and Hendrix MJC.  (2006)  Influence of the microenvironment on melanoma cell fate determination and phenotype.  Cancer Research:  66:7833-36.
 
Topczewska JM*, Postovit LM*, Margaryan NV, Sam A, Hess AR, Wheaton WW, Nickoloff B, Topczewski J, and Hendrix MJC.  (2006) Embryonic and tumorigenic pathways converge via Nodal signaling:  Role in melanoma aggressiveness.  Nature Medicine:  Aug.12(8):925-32.  *Authors contributed equally.
 
Postovit LM*, Seftor EA*, Seftor REB, and Hendrix MJC.  (2006)  A 3-D model to study the epigenetic effects induced by the microenvironment of human embryonic stem cells.  Stem Cells:  24:501-5.
 
Postovit LM, Adams MA, Lash GE, Heaton, JPW, and Graham CH.  (2004).  Nitric oxide-mediated regulation of hypoxia-induced B16F10 melanoma metastasis.  International Journal of Cancer:  108(1): 47-53.
 
Postovit LM, Adams MA, Lash GE, Heaton JP, and Graham CH.  (2002).  Oxygen-mediated regulation of tumour cell invasiveness: involvement of a nitric oxide signalling pathway.  Journal of Biological Chemistry:  277(38):35730-7.