W. Richard McCombie
Professor
Davis Family Professor of Human Genetics
Cancer Center Member
Ph.D., University of Michigan, 1982
mccombie@cshl.edu | 516-422-4083
Over the last two decades, revolutionary improvements in DNA sequencing technology have made it faster, more accurate, and much cheaper. We are now able to sequence up to 10 trillion DNA letters in just one month. I harness these technological advancements to assemble genomes for a variety of organisms and probe the genetic basis of neurological disorders, including autism and schizophrenia, better understand cancer progression and understand the complex structures of the genomes of higher plants.
The insights of W. Richard McCombie and colleagues have led to the introduction and optimization of novel methods of high-throughput genome sequencing. His team has made it possible to catalog variation among individual organisms in a way that would have been unthinkable 10 years ago. They have brought online a new generation of Illumina sequencers and optimized their function to a level at which eight to 10 trillion DNA bases can be sequenced in a month. McCombie’s team has been involved in international efforts culminating in genome sequences for maize, rice, bread wheat—three of the world’s most important food crops. They have also had an important role in projects to sequence the flowering plant Arabidopsis thaliana (the first plant genome sequence), the fission yeast Schizosaccharomyces pombe, as well as the human genome and other important genomes. McCombie’s group is currently involved in several important projects to resequence genes in patient samples that are of special interest to human health, including DISC1 (a strong candidate gene for schizophrenia), looking for genetic variants implicated in bipolar illness and major recurrent depression. They are also looking for genes, that contribute to cancer progression using whole genome sequencing or a method called exome sequencing which they developed with Greg Hannon to look at mutations in the regions of the genome that code for proteins.
CSHL professors on the cutting edge of scientific research
November 21, 2022
Four CSHL researchers were ranked among the world’s most cited in 2022.
President’s essay: Foundations for the future
May 25, 2022
Strategically designed to spark scientific exchange and inspiration, CSHL is a unique research and education environment for advancing science.
New genetic research to understand racial disparity in cancers
September 8, 2020
Cold Spring Harbor Laboratory will study the genetic contributions of ethnicity to colon, endometrial, and pancreas cancers in African Americans.
CSHL investigators rank among world’s most highly cited
December 11, 2019
Seven researchers affiliated with CSHL are among the scientists producing the top 1 percent of the most highly-cited research in the world.
An essay from the President: Biology for the planet
May 16, 2019
CSHL plant scientists are looking for solutions to the biggest questions in agriculture as environments are reshaped by climate change.
Base Pairs Episode 17: Genomes, justice, and the journey here
September 15, 2018
A look at how gene-mapping works, what scientists can tell by looking at your genome, and what it means for your privacy.
Genomes, justice, and the journey here
September 15, 2018
CSHL Professor W. Richard McCombie discusses genomic privacy and sequencing technology in this episode of Base Pairs.
Massive genome havoc in breast cancer is revealed
July 12, 2018
Researchers have made a highly detailed map of 20,000 structural variations in a cancer cell’s genome
Portrait of a Neuroscience Powerhouse
April 27, 2018
A relatively small neuroscience group at CSHL is having an outsized impact on a dynamic and highly competitive field
New study casts sharpest light yet on genetic mysteries of autism
October 29, 2014
Our picture of how genetic errors contribute to autism has just gotten sharper.
All Publications
Era of gapless plant genomes: innovations in sequencing and mapping technologies revolutionize genomics and breeding
12 Jan 2023 | Current Opinion in Biotechnology | 79:102886
Gladman, Nicholas, Goodwin, Sara, Chougule, Kapeel, Richard McCombie, William, Ware, Doreen
Familial long-read sequencing increases yield of de novo mutations
9 Mar 2022 | American Journal of Human Genetics
Noyes, Michelle, Harvey, William, Porubsky, David, Sulovari, Arvis, Li, Ruiyang, Rose, Nicholas, Audano, Peter, Munson, Katherine, Lewis, Alexandra, Hoekzema, Kendra, Mantere, Tuomo, Graves-Lindsay, Tina, Sanders, Ashley, Goodwin, Sara, Kramer, Melissa, Mokrab, Younes, Zody, Michael, Hoischen, Alexander, Korbel, Jan, McCombie, W, Eichler, Evan
Patient-derived triple-negative breast cancer organoids provide robust model systems that recapitulate tumor-intrinsic characteristics
18 Feb 2022 | Cancer Research
Bhatia, Sonam, Kramer, Melissa, Russo, Suzanne, Naik, Payal, Arun, Gayatri, Brophy, Kyle, Andrews, Peter, Fan, Cheng, Perou, Charles, Preall, Jonathan, Ha, Taehoon, Plenker, Dennis, Tuveson, David, Rishi, Arvind, Wilkinson, John, McCombie, W, Kostroff, Karen, Spector, David
SLC5A3-dependent myo-inositol auxotrophy in acute myeloid leukemia.
16 Sep 2021 | Cancer Discovery | :candisc.1849.2020
Wei, Yiliang, Huang, Yu-Han, Skopelitis, Damianos, Iyer, Shruti, Costa, Ana, Yang, Zhaolin, Kramer, Melissa, Adelman, Emmalee, Klingbeil, Olaf, Demerdash, Osama, Polyanskaya, Sofya, Chang, Kenneth, Goodwin, Sara, Hodges, Emily, McCombie, W, Figueroa, Maria, Vakoc, Christopher
Transcriptional silencing of ALDH2 confers a dependency on Fanconi anemia proteins in acute myeloid leukemia.
23 Apr 2021 | Cancer Discovery
Yang, Zhaolin, Wu, Xiaoli, Wei, Yiliang, Polyanskaya, Sofya, Iyer, Shruti, Jung, Moonjung, Lach, Francis, Adelman, Emmalee, Klingbeil, Olaf, Milazzo, Joseph, Kramer, Melissa, Demerdash, Osama, Chang, Kenneth, Goodwin, Sara, Hodges, Emily, McCombie, W, Figueroa, Maria, Smogorzewska, Agata, Vakoc, Christopher
Impact of preoperative antibiotics and other variables on integrated microbiome-host transcriptomic data generated from colorectal cancer resections.
14 Apr 2021 | World Journal of Gastroenterology | 27(14):1465-1482
Malik, Sarah, Zhu, Chencan, Li, Jinyu, LaComb, Joseph, Denoya, Paula, Kravets, Igor, Miller, Joshua, Yang, Jie, Kramer, Melissa, McCombie, W, Robertson, Charles, Frank, Daniel, Li, Ellen
The human Origin Recognition Complex is essential for pre-RC assembly, mitosis and maintenance of nuclear structure.
1 Feb 2021 | eLife | 10
Chou, Hsiang-Chen, Bhalla, Kuhulika, Demerdesh, Osama, Klingbeil, Olaf, Hanington, Kaarina, Aganezov, Sergey, Andrews, Peter, Alsudani, Habeeb, Chang, Kenneth, Vakoc, Christopher, Schatz, Michael, McCombie, W, Stillman, Bruce
Comprehensive analysis of structural variants in breast cancer genomes using single-molecule sequencing
Sep 2020 | Genome Research | 30(9):1258-1273
Aganezov, S, Goodwin, S, Sherman, R, Sedlazeck, F, Arun, G, Bhatia, S, Lee, I, Kirsche, M, Wappel, R, Kramer, M, Kostroff, K, Spector, D, Timp, W, McCombie, W, Schatz, M
Unraveling molecular mechanisms of immunity and cancer-resistance using the genomes of the Neotropical bats Artibeus jamaicensis and Pteronotus mesoamericanus
9 Sep 2020 | BioRxiv
Scheben, Armin, Ramos, Olivia, Kramer, Melissa, Goodwin, Sara, Oppenheim, Sara, Becker, Daniel, Schatz, Michael, Simmons, Nancy, Siepel, Adam, McCombie, Richard
The human Origin Recognition Complex is essential for pre-RC assembly, mitosis and maintenance of nuclear structure
6 Aug 2020 | BioRxiv
Chou, H, Bhalla, K, El Demerdash, O, Klingbeil, O, Hanington, Kaarina, Aganezov, S, Andrews, P, Alsudani, H, Chang, K, Vakoc, C, Schatz, M, McCombie, W, Stillman, B