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.
From plant genomics to a bioscience revolution
March 25, 2024
CSHL played a lead role in mapping the first plant genome. Today, that breakthrough fuels a whole new understanding of life on Earth.
A quiz for the ages
January 29, 2024
Want to know the secret to a long life? So do CSHL scientists. Take this short quiz to see what they’ve found out about aging and longevity.
From cancer genetics to cancer treatments
January 18, 2024
One cancer gene, one cancer genome, two Cold Spring Harbor Laboratory discoveries that helped shape the face of modern cancer medicine.
Holy immunity! Bat genes key against COVID, cancer
October 16, 2023
Rapid evolution has streamlined bats’ immune systems. This may explain why they’re resistant to cancer and viruses like Ebola or COVID-19.
The evolution of autism research
May 25, 2023
The conversation around autism has evolved over the past two decades. So has CSHL research. This retrospective shows how we’ve helped move the needle.
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.
All Publications
Gapless assembly of complete human and plant chromosomes using only nanopore sequencing
17 Mar 2024 | bioRxiv
Koren, Sergey, Bao, Zhigui, Guarracino, Andrea, Ou, Shujun, Goodwin, Sara, Jenike, Katharine, Lucas, Julian, McNulty, Brandy, Park, Jimin, Rautianinen, Mikko, Rhie, Arang, Roelofs, Dick, Schneiders, Harrie, Vrijenhoek, Ilse, Nijbroek, Koen, Ware, Doreen, Schatz, Michael, Garrison, Erik, Huang, Sanwen, McCombie, William, Miga, Karen, Wittenberg, Alexander, Phillippy, Adam
Nanopore sequencing of 1000 Genomes Project samples to build a comprehensive catalog of human genetic variation
7 Mar 2024 | bioRxiv
Gustafson, Jonas, Gibson, Sophia, Damaraju, Nikhita, Zalusky, Miranda, Hoekzema, Kendra, Twesigomwe, David, Yang, Lei, Snead, Anthony, Richmond, Phillip, De Coster, Wouter, Olson, Nathan, Guarracino, Andrea, Li, Qiuhui, Miller, Angela, Goffena, Joy, Anderson, Zachery, Storz, Sophie, Ward, Sydney, Sinha, Maisha, Gonzaga-Jauregui, Claudia, Clarke, Wayne, Basile, Anna, Corvelo, Andre, Reeves, Catherine, Helland, Adrienne, Musunuri, Rajeeva, Revsine, Mahler, Patterson, Karynne, Paschal, Cate, Zakarian, Christina, Goodwin, Sara, Jensen, Tanner, Robb, Esther, 1000 Genomes ONT Sequencing Consortium, University of Washington Center for Rare Disease Research (UW-CR, Genomics Research to Elucidate the Genetics of Rare Diseases (GR, McCombie, W, Sedlazeck, Fritz, Zook, Justin, Montgomery, Stephen, Garrison, Erik, Kolmogorov, Mikhail, Schatz, Michael, McLaughlin, Richard, Dashnow, Harriet, Zody, Michael, Loose, Matthew, Jain, Miten, Eichler, Evan, Miller, Danny
CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods
22 Feb 2024 | Genome Biology | 25(1):53
Critical Assessment of Genome Interpretation Consortium
Long-Read Sequencing Reveals Rapid Evolution of Immunity- and Cancer-Related Genes in Bats
4 Sep 2023 | Genome Biology and Evolution | 15(9)
Scheben, Armin, Mendivil Ramos, Olivia, Kramer, Melissa, Goodwin, Sara, Oppenheim, Sara, Becker, Daniel, Schatz, Michael, Simmons, Nancy, Siepel, Adam, McCombie, W, Pfeifer, Susanne
The genome of the Wollemi pine, a critically endangered "living fossil" unchanged since the Cretaceous, reveals extensive ancient transposon activity
24 Aug 2023 | bioRxiv
Stevenson, Dennis, Ramakrishnan, Srividya, Alves, Cristiane, Coelho, Laís, Kramer, Melissa, Goodwin, Sara, Ramos, Olivia, Eshel, Gil, Sondervan, Veronica, Frangos, Samantha, Zumajo-Cardona, Cecilia, Jenike, Katherine, Ou, Shujun, Wang, Xiaojin, Lee, Yin, Loke, Stella, Rossetto, Maurizio, McPherson, Hannah, Nigris, Sebastiano, Moschin, Silvia, Little, Damon, Katari, Manpreet, Varala, Kranthi, Kolokotronis, Sergios-Orestis, Ambrose, Barbara, Croft, Larry, Coruzzi, Gloria, Schatz, Michael, McCombie, W, Martienssen, Robert
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
Correction: Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder
Sep 2021 | Molecular Psychiatry | 26(9):5251
Jia, Xiaoming, Goes, Fernando, Locke, Adam, Palmer, Duncan, Wang, Weiqing, Cohen-Woods, Sarah, Genovese, Giulio, Jackson, Anne, Jiang, Chen, Kvale, Mark, Mullins, Niamh, Nguyen, Hoang, Pirooznia, Mehdi, Rivera, Margarita, Ruderfer, Douglas, Shen, Ling, Thai, Khanh, Zawistowski, Matthew, Zhuang, Yongwen, Abecasis, Gonçalo, Akil, Huda, Bergen, Sarah, Burmeister, Margit, Chapman, Sinéad, DelaBastide, Melissa, Juréus, Anders, Kang, Hyun, Kwok, Pui-Yan, Li, Jun, Levy, Shawn, Monson, Eric, Moran, Jennifer, Sobell, Janet, Watson, Stanley, Willour, Virginia, Zöllner, Sebastian, Adolfsson, Rolf, Blackwood, Douglas, Boehnke, Michael, Breen, Gerome, Corvin, Aiden, Craddock, Nick, DiFlorio, Arianna, Hultman, Christina, Landen, Mikael, Lewis, Cathryn, McCarroll, Steven, Richard McCombie, W, McGuffin, Peter, McIntosh, Andrew, McQuillin, Andrew, Morris, Derek, Myers, Richard, O'Donovan, Michael, Ophoff, Roel, Boks, Marco, Kahn, Rene, Ouwehand, Willem, Owen, Michael, Pato, Carlos, Pato, Michele, Posthuma, Danielle, Potash, James, Reif, Andreas, Sklar, Pamela, Smoller, Jordan, Sullivan, Patrick, Vincent, John, Walters, James, Neale, Benjamin, Purcell, Shaun, Risch, Neil, Schaefer, Catherine, Stahl, Eli, Zandi, Peter, Scott, Laura