Emily Bernstein, PhD
- ASSOCIATE PROFESSOR | Oncological Sciences
- ASSOCIATE PROFESSOR | Dermatology
Research Topics:Cancer, Chromatin, Epigenetics, Gene Regulation, Molecular Biology, Stem Cells
Multi-Disciplinary Training AreaCancer Biology [CAB]
PhD, SUNY Stony Brook/Cold Spring Harbor Laboratory
The Rockefeller University
Irma T. Hirschl Charitable Trust Research Award
Tisch Cancer Institute Developmental Fund Award
Research Scholar Award
New Scholar Award
National Science Foundation Postdoctoral Fellowship
Specific Clinical/Research Interest: Our focus is on epigenetic regulation of gene expression in multiple biological pathways including cancer (melanoma and breast cancer), cellular senescence and stem cell biology. This includes various mechanisms that alter the chromatin template, including histone modifications, histone variants and their dedicated chaperones, and non-coding RNAs.
Postdoctoral Fellows: Chiara Vardabasso, Alexandre Gaspar Maia, Dan Hasson, Thomas Strub, Flavia Ghiraldini
Current Students: Chi-Yeh (Jay) Chung (GGS), Zulekha A. Qadeer (CAB), David Valle Garcia (exchange student), Zhen Sun (DSCB)
Research Assistant: Nicholas Mills
Summary of Current Research
Chromatin is the complex of DNA and its intimately associated proteins -with histones constituting the major component. This template is an attractive candidate for shaping the features of a cell's epigenetic landscape. Disruption of a cell's epigenetic balance can perturb chromatin structure and gene regulation, contributing to disease states.
Our work focuses on the study of histone variant proteins. When incorporated into chromatin, histone variants participate in diverse nuclear functions including centromeric regulation, DNA damage responses, transcriptional activation and repression, and play a role in epigenetic inheritance of chromatin states. Histone variants alter the structure and stability of the nucleosome, and provide the cell with the potential to change its post-translational modification (PTM) profile due to amino acid sequence differences from their conventional histone counterparts. We are interested in variant-specific PTMs and their binding proteins, as well as the chaperones that escort these proteins in and out of the chromatin template. We have uncovered a critical suppressive role for the histone variant macroH2A in the progression of malignant melanoma. In addition to acting as a barrier to melanoma growth and metastasis, we reported that macroH2A also acts as a barrier to induced pluripotency by repressing a set of genes required for the early stages of reprogramming.
The Polycomb Group (PcG) proteins are also focus of the lab. In mammals, there are five homologs of the single Drosophila Pc protein and it has been a longstanding goal to understand the consequences of such expansion and diversification of this protein family in both development and disease. We have previously demonstrated that each individual Pc protein is unique not only in its histone binding-specificity, but also in its association with heterochromatin (in particular, the inactive X chromosome in female mammals). Recently, we identified Cbx7 as the primary Polycomb protein expressed in ESCs, which is important for maintaining pluripotency. We have also identified novel PTMs of Cbx family members.
Our long-term goal is to understand the chromatin changes that take place at the molecular level during the transformation process of 'normal cells' to 'cancer cells' and during the reprogramming of somatic cells to stem cells. We currently have studies underway (targeted and unbiased) to identify new players in the epigenetic regulation of melanoma progression and drug resistance to targeted therapies, as these processes remain poorly understood. We are also investigating the role of histone chaperone mutations in the context of pediatric tumor biology.
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Vardabasso C, Gaspar-Maia A, Hasson D, Pünzeler S, Valle-Garcia D, Straub T, Keilhauer EC, Strub T, Dong J, Panda T, Chung CY, Yao JL, Singh R, Segura MF, Fontanals-Cirera B, Verma A, Mann M, Hernando E, Hake SB, Bernstein E. Histone Variant H2A.Z.2 Mediates Proliferation and Drug Sensitivity of Malignant Melanoma. Molecular cell 2015 Jul; 59(1).
Duarte LF, Young AR, Wang Z, Wu HA, Panda T, Kou Y, Kapoor A, Hasson D, Mills NR, Ma'ayan A, Narita M, Bernstein E. Histone H3.3 and its proteolytically processed form drive a cellular senescence programme. Nature communications 2014; 5.
Wu HA, Balsbaugh JL, Chandler H, Georgilis A, Zullow H, Shabanowitz J, Hunt DF, Gil J, Peters G, Bernstein E. Mitogen-activated protein kinase signaling mediates phosphorylation of polycomb ortholog Cbx7. The Journal of biological chemistry 2013 Dec; 288(51).
Vardabasso C, Hasson D, Ratnakumar K, Chung CY, Duarte LF, Bernstein E. Histone variants: emerging players in cancer biology. Cellular and molecular life sciences : CMLS 2013 May;.
Gaspar-Maia A, Qadeer ZA, Hasson D, Ratnakumar K, Adrian Leu N, Leroy G, Liu S, Costanzi C, Valle-Garcia D, Schaniel C, Lemischka I, Garcia B, Pehrson JR, Bernstein E. MacroH2A histone variants act as a barrier upon reprogramming towards pluripotency. Nature communications 2013 Mar; 4.
Ratnakumar K, Duarte LF, Leroy G, Hasson D, Smeets D, Vardabasso C, Bönisch C, Zeng T, Xiang B, Zhang DY, Li H, Wang X, Hake SB, Schermelleh L, Garcia BA, Bernstein E. ATRX-mediated chromatin association of histone variant macroH2A1 regulates α-globin expression. Genes & development 2012; 26: 433-438.
Chicas A, Kapoor A, Wang X, Aksoy O, Evertts AG, Zhang MQ, Garcia BA, Bernstein E, Lowe SW. H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence. Proceedings of the National Academy of Sciences of the United States of America 2012 Jun; 109(23).
O'Loghlen A, Muñoz-Cabello AM, Gaspar-Maia A, Wu HA, Banito A, Kunowska N, Racek T, Pemberton HN, Beolchi P, Lavial F, Masui O, Vermeulen M, Carroll T, Graumann J, Heard E, Dillon N, Azuara V, Snijders AP, Peters G, Bernstein E, Gil J. MicroRNA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation. Cell stem cell 2012 Jan; 10(1).