Faculty Profile

Dr. David Shechter, Ph.D.

David Shechter, Ph.D.

Associate Professor, Department of Biochemistry

Areas of Research: Chromatin biology and epigenetics in development and cancer; structural and post-translational regulation of histone chaperones; molecular mechanisms and biological function of protein arginine methyltransferases

Professional Interests

Recipes for Regulation of the Genome: Charge, Grease and Intrinsic Disorder

We are interested in understanding chromatin, the complex of DNA, histones, and other proteins that constitute the physiological form of the genome. In particular, we are interested in the role of histone post-translational modifications and histone chaperones in establishing an embryonic epigenetic state, how this process is misregulated in cancers, and how to drug components of the machinery.

Epigenetics is a phenomenon important for an overall increase in the complexity of the genome without changes in gene sequence. Post-translational modifications of histones, and deposition of histone variants, establish a “histone code” of activation or repression of transcription and other chromatin-mediated transactions, and constitute a major part of the epigenome. Epigenetic information is information content "on top of" the DNA-encoded genetic material. Epigenetic information is the landscape on which the dynamic usage of genetic information is encoded.

We utilize a wide range of techniques to broadly address these questoins, including: protein biochemistry and enzymology, structural biology, cancer cell culture, and embryos of the frog Xenopus laevis . These tools allow us to probe evolutionarily conserved mechanisms specifying critical events in chromatin biology and epigenetics. Our combined use of rigorous in vitro studies along with in vivo studies in the frog and in cancer cells provides an uncompromised approach to fully understanding epigenetic phenomena and how to apply this knowledge towards improving human health. We are currently pursuing a number of specific research avenues, including:

  • determination of the biochemical mechanisms of arginine methyltransferases (PRMT1-9) using enzymology and structural biology
  • analyzing the histone and non-histone code specified by PRMT-catalyzed histone methylation in embryos and breast and lung cancer cells
  • Determining how phosphorylation, methylation, and glutamylation of histone chaperones (including Npm1, Npm2, and Nap1) occur and how these post-translational modifications regulate histone deposition activity
  • Using quantitative techniques (hydrogen-deuterium exchange, NMR, crystallography, binding studies) to understand histone chaperone intrinsically disordered domains in the binding and release of histones

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You can obtain the TM0936 SAH Deaminase plasmid clone for our EZ-MTase asay (Burgos et al 2017) from DNASU: http://dnasu.org/DNASU/GetCloneDetail.do?cloneid=84735

Lab Chat with Dr. Shechter: http://magazine.einstein.yu.edu/winterspring-2017/lab-chat-5/ and Journal of Molecular Biology biography. 

 

Selected Publications

Selected:
  1. Emmanuel S. Burgos,  
  2. Christopher Warren and David Shechter. Fly Fishing for Histones: Catch and Release by Histone Chaperone Intrinsically Disordered Regions and Acidic Stretches. J Mol Biol2017 doi:10.1016/j.jmb.2017.06.005
  3. Wei-lin Wang and David ShechterChromatin assembly and transcriptional cross-talk in Xenopus laevis oocyte and egg extracts. Int J. Dev. Biol. 2016. doi: 10.1387/ijdb.160161ds
  4. Hongshan Chen, Benjamin Lorton, Varun Gupta, and David Shechter. A TGFβ-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repressionOncogene, Jun 2016.
  5. Takashi Onikubo, Joshua J. Nicklay, Li Xing, Christopher Warren, Brandon Anson, Wei-Lin Wang, Emmanuel S. Burgos, Sophie E. Ruff, Jeffrey Shabanowitz, R. Holland Cheng, Donald F. Hunt, and David Shechter. Developmentally Regulated Post-Translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition. Cell Reports, Mar 11 2015; doi:10.1016/j.celrep.2015.02.038
  6. Histone H2A and H4 N-Terminal Tails are Positioned by the MEP50 WD-Repeat Protein for Efficient Methylation by the PRMT5 Arginine Methyltransferase. Emmanuel S. Burgos, Carola Wilczek, Takashi Onikubo, Jeffrey B. Bonanno, Janina Jansong, Ulf Reimer and David Shechter. Journal of Biological Chemistry, 2015.
  7. The PRMT5 arginine methyltransferase: many roles in development, cancer, and beyond. Nicole Stopa, Jocelyn Krebs, David Shechter. Cellular and Molecular Life Sciences2015. 
  8. Phosphorylation and arginine methylation mark histone H2A prior to deposition during Xenopus laevis development
    Wei-Lin Wang, Lissa C Anderson, Joshua J Nicklay, Hongshan Chen, Matthew J Gamble, Jeffrey Shabanowitz, Donald F Hunt and David Shechter. Epigenetics & Chromatin, 2014 7:22
  9. Structure of the Arginine Methyltransferase PRMT5-MEP50 Reveals a Mechanism for Substrate Specificity Ho MC, Wilczek C, Bonanno JB, Xing L, Seznec J, Matsui T, Carter LG, Onikubo T, Kumar PR, Chan MK, Brenowitz M, Cheng RH, Reimer U, Almo SC, Shechter D.(2013).PLoS ONE 8(2): e57008. doi:10.1371/journal.pone.0057008.
  10. Protein Arginine Methyltransferase Prmt5-Mep50 Methylates Histones H2A and H4 and the Histone Chaperone Nucleoplasmin in Xenopus laevis Eggs. Wilczek C, Chitta R, Woo E, Shabanowitz J, Chait BT, Hunt DF, Shechter D.. J Biol Chem2011 Dec 9;286(49):42221-31.  
  11. Laura Banszynski, C. David Allis, David Shechter. Analysis of histones and chromatin in Xenopus laevis egg and ooctye extractsMethods2010. Vol 51:1.
  12. Extraction, purification and analysis of histones. Shechter D, Dormann HL, Allis CD, Hake SB. Nature Protocols 2007;2(6):1445-57.

Research Images

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More Information About Dr. David Shechter

Shechter Lab Website - Research Interests, Lab Members, Protocols, Photos, etc

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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 304
Bronx, NY 10461

Tel: 718.430.4120
Fax: 718.430.8565

Research Information