The Drier Lab for Systems Biology of Cancer: Uncover genomewide dysregulation of regulatory elements behind cancer
Cancer is driven by genetic and epigenetic changes to the DNA. We now know quite well how genetic alterations of genes drive cancer, thanks to extensive mapping efforts. However, we still know very little about the extent and function of genetic and epigenetic alterations at regulatory regions away from genes.
Other than expanding our understanding of gene regulation and dysregulation in cancer, we aim to leverage this knowledge to predict novel therapeutic targets for the development of new drugs, and develop models to predict patient outcome to help guiding treatment plans for cancer patients.
Our scientific approach combines epigenetic profiling, development of computational models and algorithms, and experimental validation. We combine cutting edge experimental techniques with developing new machine learning algorithms and big-data analytical approaches.
We study how genetic and epigenetic alterations of regulatory DNA elements cause cancer or contribute to the disease. We focus on two types of regulatory DNA elements: enhancers (regulating transcription), and CTCF binding sites (regulating chromosomal topology, i.e. the folding of the chromosome in 3D).
Epigenetic topological alterations in cancer
Genetic dysregulation of DNA regulatory elements in cancer
We develop systematic approaches to integrate genetic, epigenetic, topologic and transcriptional information to study how genetic alterations affect the function of regulatory DNA elements. For example, we have recently uncovered how genetic translocations alter the targets of enhancers to rewire the gene regulatory network into a positive feedback loop . We are now working to extend such approaches to comprehensive analysis of functional regulatory DNA alterations across cancer.
- Large-scale implementation of pooled RNA-extraction and RT-PCR for SARS-CoV-2 detection. Ben-Ami R*, Klochendler A*, Seidel M*, Sido T, Gurel-Gurevich O, Yassour M, Meshorer E, Benedek G, Fogel I, Oiknine-Djian E, Gertler A, Rotstein Z, Lavi B, Dor Y, Wolf DG, Salton M, Drier Y, The Hebrew University-Hadassah COVID-19 diagnosis team. Clinical Microbiology and Infection 2020.
- Enhancer and super-enhancer regulation and its disruption in cancer. Drier Y. Current Opinion in Systems Biology 2020.
- Altered chromosomal topology drives oncogenic programs in SDH-deficient GISTs. Flavahan WA*, Drier Y*, Johnstone S, Tarjan D, Hegazi E, Shareef SJ, Javed NM, Raut CP, Eschle BK, Gokhale PC, Hornick JL, Sicinska ET, Demetri GD, Bernstein BE. Nature 2019, 575(7781):229–233.
- Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors. Cejas P,* Drier Y*, Dreijerink KMA, Brosens LAA, Deshpande V, Epstein CB, Conemans EB, Morsink FHM, Graham MK, Valk GD, Vriens MR, Castillo CF, Ferrone CR, Adar T, Bowden M, Whitton HJ, Da Silva A, Font-Tello A, Long HW, Gaskell E, Shoresh N, Heaphy CM, Sicinska E, Kulke MH, Chung DC, Bernstein BE, Shivdasani RA. Nature Medicine, 2019.
- Insulator dysfunction and oncogene activation in IDH mutant gliomas. Flavahan WA*, Drier Y*, Liau BB, Gillespie SM, Venteicher AS, Stemmer-Rachamimov AO, Suvà ML, Bernstein BE. Nature, 2016.
- An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma. 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. Nature Genetics, 2016.
- Detection of Enhancer-Associated Rearrangements Reveals Mechanisms of Oncogene Dysregulation in B-cell Lymphoma. Ryan RJ*,Drier Y*, Whitton H, Cotton MJ, Kaur J, Issner R, Gillespie S, Epstein CB, Nardi V, Sohani AR, Hochberg EP, Bernstein BE. Cancer Discovery, 2015.
- Pathway-based personalized analysis of cancer. Drier Y, Sheffer M, Domany E. PNAS, 2013.
- Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability. Drier Y, Lawrence MS, Carter SL, Stewart C, Gabriel SB, Lander ES, Meyerson M, Beroukhim R, Getz G. Genome Research, 2013.
- The genomic complexity of primary human prostate cancer. Berger MF*, Lawrence MS*, Demichelis F*, Drier Y*, Cibulskis K, Sivachenko AY, Sboner A, Esgueva R, Pflueger D, Sougnez C, Onofrio R, Carter SL, Park K, Habegger L, Ambrogio L, Fennell T, Parkin M, Saksena G, Voet D, Ramos AH, Pugh TJ, Wilkinson J, Fisher S, Winckler W, Mahan S, Ardlie K, Baldwin J, Simons JW, Kitabayashi N, MacDonald TY, Kantoff PW, Chin L, Gabriel SB, Gerstein MB, Golub TR, Meyerson M, Tewari A, Lander ES, Getz G, Rubin MA, Garraway LA. Nature, 2011.
We are currently recruiting talented candidates for MSc, PhD and postdoc positions, as well as Medical School students and undergraduate students for part time projects.
If you are interested email CV and recommendations to firstname.lastname@example.org