Biological and Biomedical Science
 DMS Home  /  About DMS  /  Current Student Resources  /  Contact Us  /  Search 

Kornelia Polyak

Department of Medicine
Dana-Farber Cancer Institute
44 Binney Street, D740C
Boston, MA 02115
Tel: (617) 632-2106
Fax: (617) 582-8490
Email: kornelia_polyak@dfci.harvard.edu
Webpage: The PolyakLab Page
5 postdocs, 3 visiting scientists (2 pathologists and 1 oncologist), 2 technicians, 1 graduate student

The Breast Cancer Genetics Laboratory at the Dana-Farber Cancer Institute is dedicated to the molecular analysis of human breast cancer. Human breast cancer arises as the result of a series of genetic changes. This laboratory is focusing on identifying differences between normal and cancerous breast tissue using various technologies, determining their consequences and utilizing them to improve the clinical management of breast cancer patients.

Breast cancer is a leading cause of cancer related death in women of the western world. The recent trend toward improvement in breast cancer mortality rate is largely due to increased diagnosis of early stage disease, while about 1/4 of the patients diagnosed with invasive breast carcinoma will eventually die from it. Thus, there is a need to better understand the pathophysiology of breast cancer initiation, maintenance, and progression and to use this knowledge for the design of targeted, molecular based therapies. Recently developed technologies such as microarrays and SAGE (Serial Analysis of Gene Expression) have enabled us to analyze the comprehensive gene expression profiles of normal and cancer cells at a genome-wide scale. Molecular signatures have been identified that allow the classification of breast tumors and predict clinical outcome. However, there is still a significant gap between the acquisition of this knowledge and its translation into clinical practice largely due to the fact that in addition to the identification of differences between normal and cancer cells or between different cancer types, we have to determine what are the key genetic or phenotypic alterations that play a critical role in tumorigenesis.

The goal of our lab is to identify molecular alterations involved in breast tumorigenesis using genomic approaches including SAGE, array CGH, SNP arrays, MSDK (Methylation Specific Digital Karyotyping) and tissue microarrays, analyze the functional relevance of these changes, and utilize them for the improved management of breast cancer patients. We have analyzed the gene expression profiles of normal, in situ, invasive, and metastatic breast carcinomas using SAGE and identified several genes expressed only in normal or cancer cells, or in a specific tumor stage/type. Recently we extended our studies to the individual analysis of each cell type that composes normal and cancerous breast tissue. Thus, we purified epithelial, myoepithelial, and endothelial cells, fibroblasts and infiltrating leukocytes from normal, DCIS and invasive breast cancer tissue and generated SAGE libraries from them. Based on this SAGE data we found that dramatic gene expression changes occur not only in epithelial (cancer) cells, but also in all stromal cell types. We also analyzed the genetic profile of epithelial and stromal cells from breast tumors using array CGH and SNP arrays and found genetic changes only in epithelial cells.

Currently we are focusing on the further characterization of the HIN-1 gene, understanding the role of epithelial-stromal cell interactions, and stem cells in breast tumorigenesis.

 

References:

  • 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.

  • 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.

  • Polyak K. Breast cancer: origins and evolution, J Clin Inv 2007; 117:3155-3163.