• Researcher Profile

    Kornelia Polyak, MD, PhD

     
    Kornelia Polyak, MD, PhD
     
    Professor of Medicine, Harvard Medical School

    Office phone: 617-632-2106
    Fax: 617-580-8490
    Email: kornelia_polyak@dfci.harvard.edu
    Website: Polyak Laboratory for Breast Cancer Research

    Preferred contact method: email
     
     

    Research Department

    Medical Oncology/Molecular and Cellular

    Area of Research

    Molecular Basis of Breast Tumor Evolution

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Dana 740C
    Boston, MA 02215

    Biography

    Dr. Polyak received her MD in 1991 from Albert Szent-Gyorgyi Medical University, Szeged, Hungary, and her PhD in 1995 from Cornell University/Memorial Sloan-Kettering Cancer Center. She completed a research fellowship in oncology at the Johns Hopkins Oncology Center, Baltimore, where she analyzed the mechanism of p53-mediated cell death. Joining DFCI in 1998, she is principally involved in basic laboratory research focusing on cancer genetics and the molecular basis of breast cancer.

    Recent Awards

    • AACR Outstanding Investigator Award for Breast Cancer Research, San Antonio, TX, 2012
    • Paul Marks Award for Cancer Research, Sloan-Kettering Cancer Center, New York, NY, 2011
    • Elected to the Johns Hopkins Society of Scholars, 2008
    • 27th Annual Award for Outstanding Achievement in Cancer Research, American Association for Cancer Research, 2007
    • Claire W. and Richard P. Morse Research Award, Dana-Farber Cancer Institute, 2006
    • Tisch Family Outstanding Achievement Award, Dana-Farber Cancer Institute, 2005
    • V Foundation Scholar Award, 2001
    • Sidney Kimmel Scholar Award, 1999

    Research

    Molecular Basis of Breast Tumor Evolution

    Research in my laboratory is dedicated to the molecular analysis of human breast cancer. Our goal is to identify differences between normal and cancerous breast tissue, determine their consequences, and use this information to improve the clinical management of breast cancer patients. We have devoted much effort to develop new technologies that allow for the comprehensive molecular profiling of cells isolated from primary human tissue samples. Using these methods we have been at the forefront of studies analyzing purified cell populations from normal and neoplastic human breast tissue at genomic scale and utilizing interdisciplinary approaches for the better understanding of clinical breast cancer.
    We characterized molecular alterations that occur during breast tumor progression using SAGE (Serial Analysis of Gene Expression) for gene expression profiling, SNP (Single Nucleotide Polymorphism) arrays and array CGH (Comparative Genomic Hybridization) for genetic changes, MSDK (Methylation-Specific Digital Karyotyping) for the characterization of global DNA methylation profiles, and ChIP-Seq (Chromatin Immunoprecipitation and next generation sequencing) for the analysis of histone modification patterns. In addition to analyzing the tumor cells we also investigated all cell types that compose normal breast tissue and in situ and invasive breast carcinomas. Using these approaches we determined that gene expression and epigenetic changes occur in all cell types during breast tumor progression, whereas clonally selected genetic alterations are restricted to tumor epithelial cells. Several of the genes we identified as aberrantly methylated in breast cancer, including the SCGB3A (HIN-1) gene, are candidate diagnostic or prognostic markers. Based on our results we also proposed that the in situ to invasive breast carcinoma progression is determined by interactions among epithelial, myoepithelial, and stromal cells and that progression occurs due to the loss of normal myoepithelial cell function. These findings change the way we approach breast tumor progression, the identification of patients with high risk for progression, and can be used for designing better cancer preventative interventions.
    We have also characterized cells with stem cell characteristics from normal mammary epithelium and breast carcinomas. In the normal breast, we have been investigating molecular alterations induced by factors that influence breast cancer risk including pregnancy, breast density, and hereditary mutations in breast cancer genes with the aim of better understanding these changes and exploiting them for breast cancer preventative approaches. In breast cancer, we have been analyzing mechanisms that underlie intra-tumor heterogeneity including genetic, epigenetic, and non-hereditary changes, and the clinical consequences of intra-tumor diversity with special emphasis on tumor progression and therapeutic responses. We study breast tumors as ecosystems and apply ecological and evolutionary methods to better understand the clinical implications of tumor heterogeneity.


    Select Publications

    • Porter D, Weremowicz S, Koei Chin, Seth P, Keshaviah A, Lahti-Domenici J, Bae YK, Monitto CL, Merlos-Suarez A, Chan J, Hulette CM, Richardson A, Morton CC, Marks J, Duyao M, Hruban R, Gabrielson E, Gelman R, Polyak K. A neural growth factor is a candidate oncogene in breast cancer. Proc Natl Acad Sci U S A 2003;100:10931-6.
    • Hu M, Yao J, Cai L, Bachman KE, van den Brûle F, Velculescu V, Polyak K. Distinct epigenetic changes in the stromal cells of breast cancers. Nat Genet 2005;37:899-905.
    • Allinen M, Beroukhim R, Cai, L, Brennan C, Lahti-Domenici J, Huang H, Porter D, Hu M, Chin L, Richardson A, Schnitt S, Sellers W, Polyak K. Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell 2004;6:17-32.
    • Burstein HJ, Polyak K, Wong JS, Kaelin CM. Ductal carcinoma in situ of the breast. N Engl J Med 2004;350:1430-40.
    • Shipitsin M, Campbell LL, Argani P, Weremowicz S, Noga Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak K. Molecular definition of breast tumor heterogeneity. Cancer Cell 2007; 11:259-273.
    • Boehm JB*, Zhao J*, Yao J*, Kim SY, Dunn IF, Sjostrom SK, Garraway LA, Weremowicz S, Greulich H, Stewart CJ, Mulvey LA, Ambrogio L, Hill DE, Vidal M, Meyerson M, Grenier J, Hinkle G, Root DE, Roberts TM, Lander ES, Polyak K*, Hahn WC*. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. *indicates equal first and senior authors, respectively. Cell 2007; 129:1065-1079.
    • Bloushtain-Qimron N, Yao J, Snyder EL, Shipitsin M, Campbell LL, Mani SA, Hu M, Chen H, Ustyansky V, Antosiewicz JE, Argani P, Halushka MK, Thomson JA, Pharoah P, Porgador A, Sukumar S, Parsons R, Richardson AL, Stampfer MR, Gelman RS, Nikolskaya T, Nikolsky Y, Polyak K. Cell-type specific DNA methylation patterns in the human breast. Proc Natl Acad Sci 2008; 105:14076-14081.
    • Hu M, Yao, J, Carroll DK, Weremowicz S, Chen H, Carrassco DE, Richardson AL, Violette S, Nikolskaya T, Nikolsky Y, Bauerlein EL, William C. Hahn WC, Gelman RS, Allred C, Bissell MJ, Schnitt SJ, Polyak K. Regulation of in situ to invasive breast carcinoma transition. Cancer Cell 2008; 13:394-406.
    • Hu M, Peluffo G, Chen H, Gelman R, Schnitt S, Polyak K. The role of COX-2 in epithelial-stromal cell interactions and the progression of ductal carcinoma in situ (DCIS) of the breast. Proc Natl Acad Sci 2009; 106:3372-3376.
    • Park SY, Kim HJ, Gnen M, Michor F, Polyak K. Cellular and genetic diversity in the progression of in situ to invasive breast carcinomas. J Clin Invest; 2010
    • Polyak K. Breast Cancer: Origins and Evolution, J Clin Inv 2007; 117:3155-3163.
    • Polyak K, Haviv I, Campbell IG. Co-evolution of tumor cells and their microenvironment. Trends Genet. 2009; 25:30-38.
    • Polyak K and Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell features. Nature Rev Cancer 2009; 9:265-273.

    Trainees

    • Marusyk, Andriy, PhD
    • Almendro, Vanessa, PhD
    • Su, Ying, PhD
    • Huh, Sung Jin, PhD
    • Subedee, Ashim, Sc.
    • Yamamoto, Shoji, PhD
    • Tabassum, Doris, BA
    • Peluffo, Guillermo, PhD
    • Shu, Shaokun, PhD
    • Janiszewska, Michalina, PhD
    • Zucca, Mattia, BA
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