Landau Lab
Cancer Genomics & Evolutionary Dynamics at WCM/NYGC
Selected Publications
Preprint:
Ben-Chetrit N, Nui X, Sotelo J, Swett AD, Rajasekhar VK, Jiao MS, Stewart CM, Bhardwaj P, Kottapalli S, Ganesan S, Loyher P-L, Potenski C, Hannuna A, Brown KA, Iyengar NM, Giri DD, Lowe SW, Healey JH, Geissmann F, Sagi I, Joyce JA, Landau DA. Breast cancer macrophage heterogeneity and self-renewal are determined by spatial location. bioRxiv (2023) doi:10.1101/2023.10.24.563749
Cortés-López M, Chamely P, Hawkins AG, Stanley RF, Swett AD, Ganesan S, Mouhieddine TH, Dai X, Kluegel L, Chen C, Batta K, Furer N, Vedula RS, Beaulaurier J, Drong AW, Hickey S, Dusaj N, Mullokandov G, Stasiw AM, Su J, Chaligné R, Juul S, Harrington E, Knowles DA, Potenski CJ, Wiseman DH, Tanay A, Shlush L, Lindsley RC, Ghobrial IM, Taylor J, Abdel-Wahab O, Gait, F, Landau DA. Single-cell multi-omics defines the cell-type-specific impact of splicing aberrations in human hematopoietic clonal outgrowths. Cell Stem Cell, 2023.
See article in the Cornell Daily Sun.
Ben-Chetrit N, Niu X, Swett AD, Sotelo J, Jiao MS, Stewart CM, Potenski C, Mielinis P, Roelli P, Stoeckius M, Landau DA. Integration of whole transcriptome spatial profiling with protein markers. Nature Biotechnology, 2022.
Preprint:
Schiffman JS, D’Avino AR, Prieto T, Pang Y, Fan Y, Rajagopalan S, Potenski C, Hara T, Suvà ML, Gawad C, Landau DA. Defining ancestry, heritability and plasticity of cellular phenotypes in somatic evolution. bioRxiv (2022) doi:10.1101/2022.12.28.522128.
Preprint:
Cheng AP, Widman AJ, Arora A, Rusinek I, Hooper WF, Murray R, Halmos D, Langanay T, Inghirami G, Germer S, Marton M, Manaa D, Helland A, Furatero F, McClintock J, Winterkorn L, Steinsnyder Z, Wang Y, Rajagopalan S, Alimohamed AI, Malbari MS, Saxena A, Callahan MK, Frederick DT, Spain L, Jaimovich A, Lipson D, Turajlic S, Zody MC, Altorki NK, Wolchok JD, Postow MA, Robine N, Boland G, Landau DA. Whole genome error-corrected sequencing for sensitive circulating tumor DNA cancer monitoring. bioRxiv (2022) doi:10.1101/2022.11.17.516904
Nam, AS, Dusaj, N, Izzo, F, Murali R, Myers RM, Mouhieddine T, Sotelo J, Benbarche S, Waarts M, Gaiti F, Tahri S, Levine R, Abdel-Wahab O, Godley LA, Chaligne R, Ghobrial I, Landau DA. Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation. Nature Genetics, 2022.
See News & Views piece @Nature Genetics
See Research Briefing @Nature Genetics
Preprint:
Myers RM, Izzo F, Kottapalli S, Prieto T, Dunbar A, Bowman RL, Mimitou EP, Stahl M, El Ghaity-Beckley S, Arandela J, Raviram R, Ganesan S, Mekerishvili L, Hoffman R, Chaligné R, Abdel-Wahab O, Smibert P, Marcellino B, Levine RL, Landau DA. Integrated Single-Cell Genotyping and Chromatin Accessibility Charts JAK2V617F Human Hematopoietic Differentiation. bioRxiv. (2022) doi.org/10.1101/2022.05.11.491515
Preprint:
Gaiti F, Chamely P, Hawkins AG, Cortés-López M, Swett AD, Ganesan S, Mouhieddine TH, Dai X, Kluegel L, Chen C, Batta K, Beaulaurier J, Drong AW, Hickey S, Dusaj N, Mullokandov G, Su J, Chaligné R, Juul S, Harrington E, Knowles DA, Wiseman DH, Ghobrial IM, Taylor J, Abdel-Wahab O, Landau DA. Single-cell multi-omics defines the cell-type specific impact of splicing aberrations in human hematopoietic clonal outgrowths. bioRxiv. (2022) doi.org/10.1101/2022.06.08.495292
Preprint:
Widman AJ, Shah M, Øgaard N, Khamnei CC, Frydendahl A, Deshpande A, Arora A, Zhang M, Halmos D, Bass J, Langanay T, Rajagopalan S, Steinsnyder Z, Liao W, Rasmussen MH, Jensen SO, Nors J, Therkildsen C, Sotelo J, Brand R, Shah RH, Cheng AP, Maher C, Spain L, Krause K, Frederick DT, Malbari MS, Marton M, Manaa D, Winterkorn L, Callahan MK, Boland G, Wolchok JD, Saxena A, Turajlic S, Imielinski M, Berger MF, Altorki NK, Postow MA, Robine N, Andersen CL, Landau DA. Machine learning guided signal enrichment for ultrasensitive plasma tumor burden monitoring. bioRxiv (2022) doi.org/10.1101/2022.01.17.476508
Prieto T and Landau DA. A heritable, non-genetic road to cancer evolution. Nature, 2021.
Chaligne R, Gaiti F, Silverbush D, Schiffman JS, Weisman HR, Kluegel L, Gritsch S, Deochand S, Gonzalez castro N, Richman AR, Klughammer J, Biancalani T, Muus C, Sheridan C, Alonso A, Izzo F, Park J, Rozenblatt-Rosen O, Regev A, Suva M and Landau DA. Epigenetic encoding, heritability and plasticity of glioma transcriptional cell states. Nature Genetics, 2021.
See News & Views piece @Nature Genetics
Pan H, Renaud L, Chaligne R, Bloehdorn J, Tausch E, Mertens D, Fink AM, Fischer K, Zhang C, Betel D, Gnirke A, Imielinski M, Moreaux J, Hallek M, Meissner A, Stilgenbauer A, Wu CJ, Elemento O and Landau DA. Discovery of candidate DNA methylation cancer driver genes. Cancer Discovery, 2021. See commentary @epigenie
Nam AS, Chaligne R, Landau DA. Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics. Nature Review Genetics, 2021.
Zviran A, Schulman RC, Shah M, Hill STK, Deochand S, Khamnei CC, Maloney D, Patel K, Liao W, Widman AJ, Wong P, Callahan MK, Ha G, Reed S, Rotem D, Frederick D, Sharova T, Miao B, Kim T, Gydush G, Rhoades J, Huang KY, Omans ND, Bolan P, Lipsky A, Ang C, Malbari M, Spinelli CF, Kazancioglu S, Runnels AM, Fennessey S, Stolte C, Gaiti F, Inghirami GG, Adalsteinsson V, Houck-Loomis B, Ishii J, Wolchok JD, Boland G, Robine N, Altorki NK, Landau DA. Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring. Nature Medicine, 2020.
*Highlight in Nature, selected as top 10 Clinical Research Achievement by the Clinical Research Forum
Izzo F, Lee SC, Poran A, Chaligne R, Gaiti F, Gross B, Murali R, Deochand S, Ang C, Jones PW, Nam AS, Kim KT, Kothen-Hill S, Schulman RC, Ki M, Lhoumaud P, Skok JA, Viny AD, Levine RL, Kenigsberg E, Abdel-Wahab O, Landau DA. DNA methylation disruption reshapes the hematopoietic differentiation landscape. Nature Genetics, 2020.
*Blogpost in Nature Cancer Community
Lhoumaud P, Sethia G, Izzo F, Sakellaropoulos T, Snetkova V, Vidal S, Badri S, Cornwell M, Giammartino D, Kim KT, Apostolou E, Stadfeld M, Landau DA, Skok J. EpiMethylTag: simultaneous detection of ATAC-seq or ChIP-seq signals with DNA methylation. Genome Biology, 2019.
Bolan PO, Zviran A, Brenan L, Schiffman JS, Duasj N, Goodale A, Piccioni F, Johannessen CM, Landau DA. Genotype-Fitness Maps of EGFR-Mutant Lung Adenocarcinoma Chart the Evolutionary Landscape of Resistance for Combination Therapy Optimization. Cell Systems, 2019.
Cheng Y, Luo H, Izzo F, Pickering BF, Nguyen D, Myers R, Schurer A, Gourkanti S, Bruning JC, Vu LP, Jaffrey S, Landau DA, Kharas MG. m6A RNA Methylation Maintains Hematopoietic Stem Cell Identity and Symmetric Commitment. Cell Reports, 2019.
Nam AS, Kim KT, Chaligne R, Izzo F, Ang C, Taylor J, Myers RM, Abu-Zeinah G, Brand R, Omans ND, Alonso A, Sheridan C, Mariani M, Dai X, Harrington E, Pastore A, Cubillo-Ruiz JR, Tam W, Hoffman R, Rabadan R, Scandura JM, Abdel-Wahab O, Smibert P and Landau DA. Somatic mutations and cell identity linked by Genotyping of Transcriptomes. Nature, 2019.
Gaiti F, Chaligne R, Gu H, Brand RM, Kothen-Hill S, Schulman RC, Grigorev K, Risso D, Kim KT, Huang KY, Pastore A, Alonso A, Sheridan C, Omans ND, Biederstedt E, Clement K, Wang L, Feldenfeld J, Bhavsar E, Aryee MJ, Allan JN, Furman RR, Gnirke A, Wu CJ, Meissner A and Landau DA. Epigenetic evolution and lineage histories of chronic lymphocytic leukaemia. Nature, 2019.
*Highlight in Nature Reviews Genetics
Pastore A, Gaiti F, Lu SX, Brand RM, Kulm S, Chaligne R, Gu H, Huang KY, Stamenova EK, Béguelin W, Jiang Y, Schulman RC, Kim KT, Alonso A, Allan JN, Furman RR, Gnirke A, Wu CJ, Melnick AM, Meissner A, Bernstein BE, Abdel-Wahab O and Landau DA. Corrupted coordination of epigenetic modifications leads to diverging chromatin states and transcriptional heterogeneity in CLL. Nature Communications, 2019.
*Highlight in Nature Reviews Genetics
Chaligne R, Nam AS, Landau DA. TARGET-seq Takes Aim at Cancer Evolution through Multi-omics Single-Cell Genotyping and Transcriptomics. Molecular Cell, 2019.
Taylor-Weiner A, Stewart C, Giordano T, Miller M, Rosenberg M, Macbeth A, Lennon N, Rheinbay E, Landau DA, Wu CJ, Getz G. DeTiN: overcoming tumor-in-normal contamination. Nature Methods, 2018.
Kothen-Hill ST, Zviran A, Schulman R, Maloney D, Huang KY, Omans N, Liao W, Robine N, & Landau DA. Deep learning mutation prediction enables early stage lung cancer detection in liquie biopsy. Sixth International Conference on Learning Representations, Workshop Track, 2018.
Landau DA, Sun C, Rosebock D, Herman SEM, Fein J, Sivina M, Underbayev C, Liu D, Hoellenriegel J, Farooqui MZH, Zhang W, Cibulskis C, Zviran A, Neuberg DS, Livitz D, Bozic I, Leshchiner I, Getz G, Burger JA, Wiestner A & Wu CJ. The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy. Nature Communications, 2017.
Bakhoum SF, Landau DA. Cancer Evolution: No Room for Negative Selection. Cell, 2017.
Sade-Feldman M, Jiao YJ, Chen JH, Rooney MS, Barzily-Rokni M, Eliane JP, Bjorgaard SL, Hammond MR, Vitzthum H, Blackmon SM, Frederick DT, Hazar-Rethinam M, Nadres BA, Van Seventer EE, Shukla AS, Yizhak K, Ray JP, Rosebrock D, Livitz D, Adalsteinsson V, Getz G, Duncan LM, Li B, Corcoran RB, Lawrence DP, Rachamimov A, Boland GM, Landau DA, Flaherty KT, Sullivan RJ & Hacohen N. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nature Communications, 2017 May.
Bakhoum SF, Landau DA. Chromosomal Instability as a Driver of Tumor Heterogeneity and Evolution. Cold Spring Harb Perspect Med, 2017.
Burger J*, Landau DA*, Taylor-Weiner A*, Bozic I*, Zhang H*, Sarosiek K, Wang L, Stewart C, Fan J, Hoellenriegel J, Sivina M, Dubuc A, Fraser C, Han Y, Li S, Livak KJ, Zou L, Wan Y, Konoplev S, Cibulskis C, Brown J, Abruzzo LV, Carter S, Keating M, Davids M, Wierda WG, Cibulskis K, Zenz T, Werner L, Dal Cin P, Kharchenko P, Neuberg D, Kantarjian H, Lander ES, Gabriel S, O'Brien S, Letai A, Weitz D, Nowak M, Getz G, and Wu CJ. Clonal evolution in patients with chronic lymphocytic leukemia developing resistance to BTK inhibition. Nature Communications, 2016.
Izzo F, Landau DA. Genetic and Epigenetic Determinants of B-cell Lymphoma Evolution. Current Opinion in Hematology, 2016.
Edelmann J, Tausch E, Landau DA, Robrecht S, Bahlo J, Fischer K, Fink AM, Bloehdorn J, Holzmann K, Böttcher S, Werner L, Kneba M, Gribben JG, Neuberg DS, Wu CJ, Hallek M, Döhner H, Stilgenbauer S. Frequent evolution of copy number alterations in CLL following first-line treatment with FC(R) is enriched with TP53 alterations: results from the CLL8 trial. Leukemia.
Wang L, Brooks AN, Fan J, Wan Y, Gambe R, Li S, Hergert S, Yin S, Freeman SS, Levin JZ, Fan L, Seiler M, Buonamici S, Smith PG, Chau KF, Cibulskis CL, Zhang W, Rassenti LZ, Ghia EM, Kipps TJ, Fernandes S, Bloch DB, Kotliar D, Landau DA, Shukla SA, Aster JC, Reed R, DeLuca D, Brown JR, Neuberg D, Getz G, Livak KJ, Meyerson MM, Kharchenko PV, Wu CJ. Transcriptomic Characterization of SF3B1 Mutation Reveals Its Pleiotropic Effects in Chronic Lymphocytic Leukemia. Cancer Cell, 2016.
Manier S, Salem K, Park J, Landau DA, Getz G, Ghobrial I. Genomic complexity in Multiple Myeloma and its clinical implication. Nature Reviews Clinical Oncology, 2016.
Landau DA*, Tausch E*, Taylor-Weiner AN*, Stewart C, Reiter JG, Bahlo J, Kluth S, Bozic I, Lawrence M, Bottcher S, Cibulskis K, Mertens D, Sougnez C, Rosenberg M, Hess JM, Carter SL, Edelmann J, Kless S, Fink A, Fischer K, Gabriel S, Lander ES, Nowak MA, Dohner H, Hallek M, Neuberg D, Getz G*, Stilgenbauer S*, Wu CJ*. Mutations driving CLL and their evolution in progression and relapse. Nature, 2015.
Landau DA*, Clement K*, Ziller MZ, Boyle P, Fan J, Gu H, Stevenson K, Sougnez C, Wang L, Li S, Zhang W, Ghandi M, Garraway G, Fernandes SM, Livak KJ, Gabriel S, Gnirke A, Lander ES, Brown JR, Neuberg D, Kharchenko PV, Hacohen N, Getz G*, Meissner A*, Wu CJ*. Locally disordered methylation forms the basis of intra-tumor methylome variation in chronic lymphocytic leukemia. Cancer Cell, 2014.
Comment: Cancer Cell.
Landau DA, Carter SL, Getz G, Wu CJ. Clonal evolution in hematologic malignancies and therapeutic implications. Leukemia, 2014.
Gress RA, Miller JS, Battiwalla M, Bishop MR, Giralt SA, Hardy NM, Kroger N, Wayne AS, Landau DA, Wu CJ. Proceedings from the National Cancer Institute¹s Second International Workshop on the Biology, Prevention, and Treatment of Relapse After Hematopoietic Stem Cell Transplantation: Biology of Relapse after Transplantation. BBMT 2013.
Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, Kiezun A, Hammerman PS, McKenna A, Drier Y, Zou L, Ramos AH, Pugh TJ, Stransky N, Helman E, Kim J, Sougnez C, Ambrogio L, Nickerson E, Shefler E, Cortés ML, Auclair D, Saksena G, Voet D, Noble M, DiCara D, Lin P, Lichtenstein L, Heiman DI, Fennell T, Imielinski M, Hernandez B, Hodis E, Baca S, Dulak AM, Lohr J, Landau DA, Wu CJ, Melendez-Zajgla J, Hidalgo-Miranda A, Koren A, McCarroll SA, Mora J, Lee RS, Crompton B, Onofrio R, Parkin M, Winckler W, Ardlie K, Gabriel SB, Roberts CW, Biegel JA, Stegmaier K, Bass AJ, Garraway LA, Meyerson M, Golub TR, Gordenin DA, Sunyaev S, Lander ES, Getz G. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature, 2013.
Landau DA, Wu CJ. Chronic lymphocytic leukemia: molecular heterogeneity revealed by high-throughput genomics. Genome Medicine, 2013.
Landau DA*, Carter SL*, Stojanov P*, McKenna A, Stevenson K, Lawrence MS, Sougnez C, Stewart C, Sivachenko A, Wang L, Wan Y, Zhang W, Shukla SA, Vartanov A, Fernandes SM, Saksena G, Cibulskis K, Tesar B, Gabriel S, Hacohen N, Meyerson M, Lander ES, Neuberg D, Brown JR, Getz G*, Wu CJ*. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell, 2013.
Comment: Nature Genetics, Nature Reviews Cancer, Nature Medicine: Notable advances 2013.
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