W. Richard McCombie

W. Richard McCombie

Davis Family Professor of Human Genetics
Cancer Center Member

Ph.D., University of Michigan, 1982

mccombie@cshl.edu | 516-422-4083

McCombie Lab Website   Faculty Profile

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.

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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

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