Andrew Chess, MD
img_Andrew Chess
PROFESSOR | Genetics and Genomic Sciences
PROFESSOR | Cell, Developmental & Regenerative Biology
PROFESSOR | Neuroscience
Research Topics
Epigenetics, Genetics, Human Genetics and Genetic Disorders
Multi-Disciplinary Training Area
Genetics and Genomic Sciences [GGS]

A longstanding interest of the Chess lab is the study of unusual mechanisms involved in regulating gene expression. Recently we have been developing approaches to allow the study of epigenetic regulation at the scale of the entire human genome. Understanding of epigenetic mechanisms is essential to understanding normal development and disease. The Chess Lab website will have more information ( ).


DNA Methylation


DNA methylation stands out amongst epigenetic marks in that it is a covalent modification of the DNA molecule itself (albeit a modification that doesn’t change the DNA sequence). For DNA methylation (specifically methylation of cytosines within CpG dinucleotides) there is a known mechanism for replicating the mark. The DNA methyltransferase I encodes a protein which recognizes hemi-methylated DNA (arising from the replication of a double-stranded methylated DNA molecule) and methylates the other strand. Genome-scale analyses of DNA methylation have led to the first demonstration of methylation of the gene body (the entire transcribed region) of mammalian genes. This work also showed more methylation on the active X than the inactive X in female cells (Hellman and Chess, 2007). These observations resulted from our decision to consider all types of CpGs rather than earlier studies that focused on CpG islands. Gene body methylation, which is present in plant genomes as well as animal genomes, adds another layer of complexity to the role of DNA methylation in regulation of the genome.


Polymorphism in DNA sequence is well known, but until recently the potential for DNA methylation polymorphism was not explored. We and others have found evidence for such DNA methylation polymorphism. Our genome-scale analyses have revealed an interesting interplay between DNA sequence polymorphism and DNA methylation polymorphism (Hellman and Chess, 2010).


Random monoallelic expression


Monoallelic expression represents a good model system for studying epigenetics because it requires the differential treatment of two alleles (which are sometimes identical in sequence). Monoallelic expression with random choice between the maternal and paternal alleles defines an unusual class of genes comprising X-inactivated genes and a few autosomal gene-families. Using a genome-wide approach, a few years ago we assessed allele-specific transcription of ~4,000 human genes in clonal cell lines and found that over 300 were subject to random monoallelic expression (Gimelbrant et al., 2007). For a majority of monoallelic genes, they observed some clonal lines displaying biallelic expression. Clonal cell lines reflect an independent choice to express the maternal, the paternal, or both alleles for each of these genes. This can lead to differences in expressed protein sequence, and to differences in levels of gene expression.


Widespread monoallelic expression suggests a mechanism that generates diversity in individual human cells and their clonal descendants. We have extended these observations to the mouse genome (in preparation, 2011).


Some other highlights


Discovery of allelic exclusion of mouse odorant receptor genes (Chess et al., 1996).


Identification of the odorant receptor gene family in Drosophila, along with the demonstration that different olfactory neurons express different receptors and converge in their projections to the antennal lobe creating a spatial representation of olfactory space (Gao and Chess, 1999; Gao et al., 2000).


Elucidation of a role for asynchronous replication in immunoglobulin gene allelic exclusion (Mostoslavsky et al., 2001).


Demonstration of chromosome-level coordination of replication timing in mouse and human cells (Singh et al., 2003; Ensminger and Chess, 2004).


Cloning of a mouse from an olfactory neuron (Eggan et al., 2004).


Insights into the evolution of the odorant receptor gene family in humans (Gimelbrant et al., 2004).


Uncovering a role for alternative splicing in the specification of unique identity of neurons (Neves et al., 2004; Zhan et al., 2004).


Discovery of a non-coding RNAs associated with nuclear structures, and the demonstration that one of them, NEAT1, plays a structural role in the nuclear parapspeckle (Hutchinson et al., 2007; Clemson et al., 2009).


Selected Publications

Control-independent mosaic single nucleotide variant detection with DeepMosaic. Xiaoxu Yang, Xin Xu, Martin W. Breuss, Danny Antaki, Laurel L. Ball, Changuk Chung, Jiawei Shen, Chen Li, Renee D. George, Yifan Wang, Taejeong Bae, Yuhe Cheng, Alexej Abyzov, Liping Wei, Ludmil B. Alexandrov, Jonathan L. Sebat, Dan Averbuj, Subhojit Roy, Eric Courchesne, August Y. Huang, Alissa D’Gama, Caroline Dias, Christopher A. Walsh, Javier Ganz, Michael Lodato, Michael Miller, Pengpeng Li, Rachel Rodin, Robert Hill, Sara Bizzotto, Sattar Khoshkhoo, Zinan Zhou, Alice Lee, Alison Barton, Alon Galor, Chong Chu, Craig Bohrson, Doga Gulhan, Eduardo Maury, Elaine Lim, Euncheon Lim, Giorgio Melloni, Isidro Cortes, Jake Lee, Joe Luquette, Lixing Yang, Maxwell Sherman, Michael Coulter, Andrew J. Chess, Schahram Akbarian. Nature Biotechnology

Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development. Changuk Chung, Xiaoxu Yang, Taejeong Bae, Keng Ioi Vong, Swapnil Mittal, Catharina Donkels, H. Westley Phillips, Zhen Li, Ashley P.L. Marsh, Martin W. Breuss, Laurel L. Ball, Camila Araújo Bernardino Garcia, Renee D. George, Jing Gu, Mingchu Xu, Chelsea Barrows, Kiely N. James, Valentina Stanley, Anna S. Nidhiry, Sami Khoury, Gabrielle Howe, Emily Riley, Xin Xu, Brett Copeland, Yifan Wang, Se Hoon Kim, Hoon Chul Kang, Andreas Schulze-Bonhage, Carola A. Haas, Horst Urbach, Marco Prinz, David D. Limbrick, Christina A. Gurnett, Matthew D. Smyth, Shifteh Sattar, Mark Nespeca, David D. Gonda, Katsumi Imai, Yukitoshi Takahashi, Hsin Hung Chen, Jin Wu Tsai, Valerio Conti, Renzo Guerrini, Orrin Devinsky, Wilson A. Silva, Helio R. Machado, Gary W. Mathern, Alexej Abyzov, Andrew J. Chess, Schahram Akbarian. Nature Genetics

Population-level variation in enhancer expression identifies disease mechanisms in the human brain. Pengfei Dong, Gabriel E. Hoffman, Pasha Apontes, Jaroslav Bendl, Samir Rahman, Michael B. Fernando, Biao Zeng, James M. Vicari, Wen Zhang, Kiran Girdhar, Kayla G. Townsley, Ruth Misir, Andrew Chess, Attila Gulyás-Kovács, Bibi Kassim, Eva Xia, Joseph D. Buxbaum, Laura Sloofman, Lizette Couto, Mariana Amaro, Marina Iskhakova, Michael Breen, Olivia Devillers, Schahram Akbarian, Shan Jiang, Steven P. Kleopoulos, Yixian Ma, Yungil Kim, Sabina Berretta, Ajeet Mandal, Barbara K. Lipska, Francis McMahon, Pavan K. Auluck, Stefano Marenco, Kelsey S. Montgomery, Mette A. Peters, Solveig K. Sieberts, Chang Gyu Hahn, Raquel Gur, Jiebiao Wang, Bernie Devlin, David A. Lewis, Lambertus Klei, Enrico Domenici, Michele Filosi, Kristen J. Brennand, Vahram Haroutunian, Georgios Voloudakis, John F. Fullard, Panos Roussos. Nature Genetics

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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.

Below are financial relationships with industry reported by Dr. Chess during 2022 and/or 2023. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Other activities: Examples include, but are not limited to, committee participation, data safety monitoring board (DSMB) membership

  • CommonMind Consortium

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.