Photo of Birgit Knoechel,  MD, PhD

Birgit Knoechel, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute

Birgit Knoechel, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Assistant Professor, Pediatrics, Harvard Medical School
  • Assistant Professor, Pediatric Oncology, Dana-Farber Cancer Institute
  • Assistant Professor, Hematology/Oncology, Boston Children's Hospital
  • Associate Member, Cancer Program, Broad Institute of MIT and Harvard

DF/HCC PROGRAM AFFILIATION

Research Abstract

Perhaps one of the most remarkable results from the genomic sequencing efforts in cancer over the past several years has been the growing number of mutations in epigenetic regulators in cancer. Detailed mechanistic analysis of epigenetic modifications and the contribution of individual chromatin regulators to these modifications have long been hindered by a lack of effective technologies. With the use of next generation sequencing techniques combined with chromatin immunoprecipitation and genome editing tools it is now possible to comprehensively investigate the molecular mechanisms of epigenetic alterations and define their disease relevance. This is critically important for designing therapeutic targeting of epigenetic modifiers and novel biomarkers that measure their effect and predict responses.

The laboratory combines functional perturbation of chromatin regulators with modern next-generation sequencing tools for chromatin state analysis to identify, mechanistically characterize, and therapeutically validate epigenetic dependencies in cancer. Specifically, we are investigating epigenetic mechanisms of drug resistance in T-cell acute lymphoblastic leukemia and are studying the evolution of epigenetic states in pediatric solid tumors.

Publications

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  • Drier Y, Cotton MJ, Williamson KE, Gillespie SM, Ryan RJ, Kluk MJ, Carey CD, Rodig SJ, Sholl LM, Afrogheh AH, Faquin WC, Queimado L, Qi J, Wick MJ, El-Naggar AK, Bradner JE, Moskaluk CA, Aster JC, Knoechel B, Bernstein BE. An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma. Nat Genet 2016. PubMed
  • Knoechel B, Aster JC. Metabolic Mechanisms of Drug Resistance in Leukemia. Cell Metab 2015; 22:759-60. PubMed
  • Yashiro-Ohtani Y, Wang H, Zang C, Arnett KL, Bailis W, Ho Y, Knoechel B, Lanauze C, Louis L, Forsyth KS, Chen S, Chung Y, Schug J, Blobel GA, Liebhaber SA, Bernstein BE, Blacklow SC, Liu XS, Aster JC, Pear WS. Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T cell leukemia. Proc Natl Acad Sci U S A 2014; 111:E4946-53. PubMed
  • Riggi N, Knoechel B, Gillespie SM, Rheinbay E, Boulay G, Suvà ML, Rossetti NE, Boonseng WE, Oksuz O, Cook EB, Formey A, Patel A, Gymrek M, Thapar V, Deshpande V, Ting DT, Hornicek FJ, Nielsen GP, Stamenkovic I, Aryee MJ, Bernstein BE, Rivera MN. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell 2014; 26:668-81. PubMed
  • Stoeck A, Lejnine S, Truong A, Pan L, Wang H, Zang C, Yuan J, Ware C, MacLean J, Garrett-Engele PW, Kluk M, Laskey J, Haines BB, Moskaluk C, Zawel L, Fawell S, Gilliland G, Zhang T, Kremer BE, Knoechel B, Bernstein BE, Pear WS, Liu XS, Aster JC, Sathyanarayanan S. Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma. 2014; 4:1154-67. PubMed
  • Knoechel B, Roderick JE, Williamson KE, Zhu J, Lohr JG, Cotton MJ, Gillespie SM, Fernandez D, Ku M, Wang H, Piccioni F, Silver SJ, Jain M, Pearson D, Kluk MJ, Ott CJ, Shultz LD, Brehm MA, Greiner DL, Gutierrez A, Stegmaier K, Kung AL, Root DE, Bradner JE, Aster JC, Kelliher MA, Bernstein BE. An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia. Nat Genet 2014; 46:364-70. PubMed
  • Lohr JG, Stojanov P, Carter SL, Cruz-Gordillo P, Lawrence MS, Auclair D, Sougnez C, Knoechel B, Gould J, Saksena G, Cibulskis K, McKenna A, Chapman MA, Straussman R, Levy J, Perkins LM, Keats JJ, Schumacher SE, Rosenberg M, , Getz G, Golub TR. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell 2014; 25:91-101. PubMed
  • Knoechel B, Lohr JG. Genomics of lymphoid malignancies reveal major activation pathways in lymphocytes. J Autoimmun 2013; 45:15-23. PubMed
  • Kluk MJ, Ashworth T, Wang H, Knoechel B, Mason EF, Morgan EA, Dorfman D, Pinkus G, Weigert O, Hornick JL, Chirieac LR, Hirsch M, Oh DJ, South AP, Leigh IM, Pourreyron C, Cassidy AJ, Deangelo DJ, Weinstock DM, Krop IE, Dillon D, Brock JE, Lazar AJ, Peto M, Cho RJ, Stoeck A, Haines BB, Sathayanrayanan S, Rodig S, Aster JC. Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry. PLoS ONE 2013; 8:e67306. PubMed
  • Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, Cruz-Gordillo P, Knoechel B, Asmann YW, Slager SL, Novak AJ, Dogan A, Ansell SM, Link BK, Zou L, Gould J, Saksena G, Stransky N, Rangel-Escareño C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Hernández-Lemus E, Schwarz-Cruz y Celis A, Imaz-Rosshandler I, Ojesina AI, Jung J, Pedamallu CS, Lander ES, Habermann TM, Cerhan JR, Shipp MA, Getz G, Golub TR. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci U S A 2012; 109:3879-84. PubMed