Paz Polak, PhD Email Paz Polak
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- Positions
- ASSISTANT PROFESSOR | Oncological Sciences
- ASSISTANT PROFESSOR | Genetics and Genomic Sciences
- ASSISTANT PROFESSOR | Medicine, Hematology and Medical Oncology
- ASSISTANT PROFESSOR | Pathology
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- Language
- English
Cancer genome studies typically focus on the foreground—the genes in the tumor itself that are mutated and that are likely to be important in driving cancer. However, the background, or tumor environment, is an important component of cancer that can serve as a powerful biomarker for the success of treatments as well as development of preventive interventions. Characterizing the complex features of the tumor environment can improve discovery of cancer genes and reveal the architecture of mutational processes. Findings from this research can help identify patients who may benefit from specific treatments and therapies such as PARP inhibitors and immunotherapies. Unfortunately, most genomic studies to date of both the tumor and the tumor environment have lacked representation from populations of diverse ethnicity, and findings are therefore not necessarily applicable across all population groups.
At Mount Sinai, my lab studies cancer driver events and cancer etiology across understudied populations (e.g. African Americans, Puerto Ricans, Dominicans, Haitians) with the goals of lowering death rates from cancer and improving overall health. These studies build upon my previous research that has revealed the complex interplay between mutations in DNA repair genes like BRCA1, BRCA2, RAD51C, ERCC2, POLE, MLH1, and MSH2, and the mutational landscape of cancer. Most importantly, this research will enable us to examine if current and future genomic assays give similar results across all populations and, if not, tailor assays accordingly to identify the most effective, personalized treatment for each patient.
My lab will also focus on understanding the contributions of physical activity and exercise to general health by utilizing different genomic approaches to assess fitness levels and changes during exercise. Physical activity and nutrition are known to be highly effective at preventing disease and improving outcomes for cancer patients. However, little is known about the actual mechanisms.
Research Topics
Bioinformatics, Breast Cancer, Cancer, Cancer Genetics, DNA Repair, Diversity, Genetics, Genomics, Global Health, Mathematical and Computational Biology
Education
BSc, Technion, Department of Physics
MSc, Technion, Department of Mathematics
MSc, The Weizmann Institute of Science, Department of Physics
PhD, Freie Universität (Max Planck Institute for Molecular Genetics)
, Harvard Medical School, Department of Medicine
Language
English
Polak P, Kim J, Braunstein LZ, Karlic R, Haradhavala NJ, Tiao G, Rosebrock D, Livitz D, Kübler K, Mouw KW, Kamburov A, Maruvka YE, Leshchiner I, Lander ES, Golub TR, Zick A, Orthwein A, Lawrence MS, Batra RN, Caldas C, Haber DA, Laird PW, Shen H, Ellisen LW, D'Andrea AD, Chanock SJ, Foulkes WD, Getz G. A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer. Nature genetics 2017 Oct; 49(10).
Kim J, Mouw KW, Polak P, Braunstein LZ, Kamburov A, Kwiatkowski DJ, Rosenberg JE, Van Allen EM, D'Andrea A, Getz G. Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors. Nature genetics 2016 06; 48(6).
Haradhvala NJ, Polak P, Stojanov P, Covington KR, Shinbrot E, Hess JM, Rheinbay E, Kim J, Maruvka YE, Braunstein LZ, Kamburov A, Hanawalt PC, Wheeler DA, Koren A, Lawrence MS, Getz G. Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair. Cell 2016 Jan; 164(3).
Francioli LC, Polak PP, Koren A, Menelaou A, Chun S, Renkens I, van Duijn CM, Swertz M, Wijmenga C, van Ommen G, Slagboom PE, Boomsma DI, Ye K, Guryev V, Arndt PF, Kloosterman WP, de Bakker PI, Sunyaev SR. Genome-wide patterns and properties of de novo mutations in humans. Nature genetics 2015 Jul; 47(7).
Polak P, Karlić R, Koren A, Thurman R, Sandstrom R, Lawrence M, Reynolds A, Rynes E, Vlahoviček K, Stamatoyannopoulos JA, Sunyaev SR. Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature 2015 Feb; 518(7539).
Polak P, Lawrence MS, Haugen E, Stoletzki N, Stojanov P, Thurman RE, Garraway LA, Mirkin S, Getz G, Stamatoyannopoulos JA, Sunyaev SR. Reduced local mutation density in regulatory DNA of cancer genomes is linked to DNA repair. Nature biotechnology 2014 Jan; 32(1).
Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, Kiezun A, Hammerman PS, McKenna A, Drier Y, Zou L, Ramos AH, Pugh TJ, Stransky N, Helman E, Kim J, Sougnez C, Ambrogio L, Nickerson E, Shefler E, Cortés ML, Auclair D, Saksena G, Voet D, Noble M, DiCara D, Lin P, Lichtenstein L, Heiman DI, Fennell T, Imielinski M, Hernandez B, Hodis E, Baca S, Dulak AM, Lohr J, Landau DA, Wu CJ, Melendez-Zajgla J, Hidalgo-Miranda A, Koren A, McCarroll SA, Mora J, Crompton B, Onofrio R, Parkin M, Winckler W, Ardlie K, Gabriel SB, Roberts CW, Biegel JA, Stegmaier K, Bass AJ, Garraway LA, Meyerson M, Golub TR, Gordenin DA, Sunyaev S, Lander ES, Getz G. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 2013 Jul; 499(7457).
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Polak has not yet completed reporting of Industry relationships.
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