The Shah lab focuses on the major topics of cancer evolution, single cell genomics and transcriptomics, mutational processes and prediction of drug response. We are interested in the major questions which underpin the cellular dynamics of cancer. Why do some cancer patients respond to treatment, while others succumb to their disease? Why are some treatments effective initially, but fail over time? How do cancer cells acquire the ability to spread from one part of the body to another? These are the fundamental yet unresolved questions which limit our understanding of cancer progression. Viewing cancer progression through the lens of evolution, our approach centers on studying cancer cells as fundamental units of information encoding biological properties that evolve in different contexts. At Memorial Sloan Kettering we are leveraging single cell technologies and cellular imaging combined with development and deployment of state of the art machine learning tools to study the cellular dynamics of cancer in patients before, during and after treatment. Our work cross cuts basic and translational science including technology and computational methods development with application to biological and clinical problems in ovarian and breast cancer.
View available career opportunities in the lab here.
Ovarian cancer mutational processes drive site-specific immune evasion. Vázquez-García I, Uhlitz F, Ceglia N, Lim JLP, Wu M, Mohibullah N, Niyazov J, Ruiz AEB, Boehm KM, Bojilova V, Fong CJ, Funnell T, Grewal D, Havasov E, Leung S, Pasha A, Patel DM, Pourmaleki M, Rusk N, Shi H, Vanguri R, Williams MJ, Zhang AW, Broach V, Chi DS, Da Cruz Paula A, Gardner GJ, Kim SH, Lennon M, Long Roche K, Sonoda Y, Zivanovic O, Kundra R, Viale A, Derakhshan FN, Geneslaw L, Issa Bhaloo S, Maroldi A, Nunez R, Pareja F, Stylianou A, Vahdatinia M, Bykov Y, Grisham RN, Liu YL, Lakhman Y, Nikolovski I, Kelly D, Gao J, Schietinger A, Hollmann TJ, Bakhoum SF, Soslow RA, Ellenson LH, Abu-Rustum NR, Aghajanian C, Friedman CF, McPherson A, Weigelt B, Zamarin D, Shah SP. Nature. 2022 Dec;612(7941):778-786.. Epub 2022 Dec 14. PMID: 36517593; PMCID: PMC9771812.
Single-cell genomic variation induced by mutational processes in cancer. Funnell T, O’Flanagan CH, Williams MJ, McPherson A, McKinney S, Kabeer F, Lee H, Salehi S, Vázquez-García I, Shi H, Leventhal E, Masud T, Eirew P, Yap D, Zhang AW, Lim JLP, Wang B, Brimhall J, Biele J, Ting J, Au V, Van Vliet M, Liu YF, Beatty S, Lai D, Pham J, Grewal D, Abrams D, Havasov E, Leung S, Bojilova V, Moore RA, Rusk N, Uhlitz F, Ceglia N, Weiner AC, Zaikova E, Douglas JM, Zamarin D, Weigelt B, Kim SH, Da Cruz Paula A, Reis-Filho JS, Martin SD, Li Y, Xu H, de Algara TR, Lee SR, Llanos VC, Huntsman DG, McAlpine JN; IMAXT Consortium; Shah SP, Aparicio S. Nature. 2022 Dec;612(7938):106-115. Epub 2022 Oct 26. PMID: 36289342; PMCID: PMC9712114.
Multimodal integration of radiology, pathology, and genomics for prediction of response to PD-(L)1 blockade in patients with non-small cell lung cancer. Vanguri RS, Luo J, Aukerman AT, Egger JV, Fong CJ, Horvat N, Pagano A, Araujo-Filho JAB, Geneslaw L, Rizvi H, Sosa R, Boehm KM, Yang SR, Bodd FM, Ventura K, Hollmann TJ, Ginsberg MS, Gao J; MSK MIND Consortium; Hellmann MD, Sauter JL, Shah SP. Nat Cancer. 2022 Oct;3(10):1151-1164.Epub 2022 Aug 29. PMID: 36038778; PMCID: PMC9586871.
Multimodal data integration using machine learning improves risk stratification of high-grade serous ovarian cancer. Boehm KM, Aherne EA, Ellenson L, Nikolovski I, Alghamdi M, Vázquez-García I, Zamarin D, Long Roche K, Liu Y, Patel D, Aukerman A, Pasha A, Rose D, Selenica P, Causa Andrieu PI, Fong C, Capanu M, Reis-Filho JS, Vanguri R, Veeraraghavan H, Gangai N, Sosa R, Leung S, McPherson A, Gao J; MSK MIND Consortium; Lakhman Y, Shah SP. Nat Cancer. 2022 Jun;3(6):723-733. Epub 2022 Jun 28. PMID: 35764743; PMCID: PMC9239907.
Clonal fitness inferred from time-series modelling of single-cell cancer genomes. Salehi S, Kabeer F, Ceglia N, Andronescu M, Williams MJ, Campbell KR, Masud T, Wang B, Biele J, Brimhall J, Gee D, Lee H, Ting J, Zhang AW, Tran H, O’Flanagan C, Dorri F, Rusk N, de Algara TR, Lee SR, Cheng BYC, Eirew P, Kono T, Pham J, Grewal D, Lai D, Moore R, Mungall AJ, Marra MA; IMAXT Consortium; McPherson A, Bouchard-Côté A, Aparicio S, Shah SP. Nature. 2021 Jul;595(7868):585-590. Epub 2021 Jun 23. PMID: 34163070; PMCID: PMC8396073.
Identification of transcriptional programs using dense vector representations defined by mutual information with GeneVector. Ceglia N, Sethna Z, Freeman SS, Uhlitz F, Bojilova V, Rusk N, Burman B, Chow A, Salehi S, Kabeer F, Aparicio S, Greenbaum BD, Shah SP, McPherson A. Nat Commun. 2023 Jul 20;14(1):4400 PMID: 37474509; PMCID: PMC10359421.
Harnessing multimodal data integration to advance precision oncology. Boehm KM, Khosravi P, Vanguri R, Gao J, Shah SP. Nat Rev Cancer. 2022 Feb;22(2):114-126. Epub 2021 Oct 18. PMID: 34663944; PMCID: PMC8810682.
Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing. Laks E, McPherson A, Zahn H, Lai D, Steif A, Brimhall J, Biele J, Wang B, Masud T, Ting J, Grewal D, Nielsen C, Leung S, Bojilova V, Smith M, Golovko O, Poon S, Eirew P, Kabeer F, Ruiz de Algara T, Lee SR, Taghiyar MJ, Huebner C, Ngo J, Chan T, Vatrt-Watts S, Walters P, Abrar N, Chan S, Wiens M, Martin L, Scott RW, Underhill TM, Chavez E, Steidl C, Da Costa D, Ma Y, Coope RJN, Corbett R, Pleasance S, Moore R, Mungall AJ, Mar C, Cafferty F, Gelmon K, Chia S; CRUK IMAXT Grand Challenge Team; Marra MA, Hansen C, Shah SP, Aparicio S. Cell. 2019 Nov 14;179(5):1207-1221.e22. PMID: 31730858; PMCID: PMC6912164.
Probabilistic cell-type assignment of single-cell RNA-seq for tumor microenvironment profiling. Zhang AW, O’Flanagan C, Chavez EA, Lim JLP, Ceglia N, McPherson A, Wiens M, Walters P, Chan T, Hewitson B, Lai D, Mottok A, Sarkozy C, Chong L, Aoki T, Wang X, Weng AP, McAlpine JN, Aparicio S, Steidl C, Campbell KR, Shah SP. Nat Methods. 2019 Oct;16(10):1007-1015. Epub 2019 Sep 9. PMID: 31501550; PMCID: PMC7485597.
Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer. Zhang AW, McPherson A, Milne K, Kroeger DR, Hamilton PT, Miranda A, Funnell T, Little N, de Souza CPE, Laan S, LeDoux S, Cochrane DR, Lim JLP, Yang W, Roth A, Smith MA, Ho J, Tse K, Zeng T, Shlafman I, Mayo MR, Moore R, Failmezger H, Heindl A, Wang YK, Bashashati A, Grewal DS, Brown SD, Lai D, Wan ANC, Nielsen CB, Huebner C, Tessier-Cloutier B, Anglesio MS, Bouchard-Côté A, Yuan Y, Wasserman WW, Gilks CB, Karnezis AN, Aparicio S, McAlpine JN, Huntsman DG, Holt RA, Nelson BH, Shah SP. Cell. 2018 Jun 14;173(7):1755-1769.e22. Epub 2018 May 10. PMID: 29754820.
Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes. Wang YK, Bashashati A, Anglesio MS, Cochrane DR, Grewal DS, Ha G, McPherson A, Horlings HM, Senz J, Prentice LM, Karnezis AN, Lai D, Aniba MR, Zhang AW, Shumansky K, Siu C, Wan A, McConechy MK, Li-Chang H, Tone A, Provencher D, de Ladurantaye M, Fleury H, Okamoto A, Yanagida S, Yanaihara N, Saito M, Mungall AJ, Moore R, Marra MA, Gilks CB, Mes-Masson AM, McAlpine JN, Aparicio S, Huntsman DG, Shah SP. Nat Genet. 2017 Jun;49(6):856-865. Epub 2017 Apr 24. PMID: 28436987.
Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer. McPherson A, Roth A, Laks E, Masud T, Bashashati A, Zhang AW, Ha G, Biele J, Yap D, Wan A, Prentice LM, Khattra J, Smith MA, Nielsen CB, Mullaly SC, Kalloger S, Karnezis A, Shumansky K, Siu C, Rosner J, Chan HL, Ho J, Melnyk N, Senz J, Yang W, Moore R, Mungall AJ, Marra MA, Bouchard-Côté A, Gilks CB, Huntsman DG, McAlpine JN, Aparicio S, Shah SP. Nat Genet. 2016 Jul;48(7):758-67. Epub 2016 May 16. PMID: 27182968.
The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, Turashvili G, Ding J, Tse K, Haffari G, Bashashati A, Prentice LM, Khattra J, Burleigh A, Yap D, Bernard V, McPherson A, Shumansky K, Crisan A, Giuliany R, Heravi-Moussavi A, Rosner J, Lai D, Birol I, Varhol R, Tam A, Dhalla N, Zeng T, Ma K, Chan SK, Griffith M, Moradian A, Cheng SW, Morin GB, Watson P, Gelmon K, Chia S, Chin SF, Curtis C, Rueda OM, Pharoah PD, Damaraju S, Mackey J, Hoon K, Harkins T, Tadigotla V, Sigaroudinia M, Gascard P, Tlsty T, Costello JF, Meyer IM, Eaves CJ, Wasserman WW, Jones S, Huntsman D, Hirst M, Caldas C, Marra MA, Aparicio S. Nature. 2012 Apr 4;486(7403):395-9. PMID: 22495314; PMCID: PMC3863681.
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Gräf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S; METABRIC Group; Langerød A, Green A, Provenzano E, Wishart G, Pinder S, Watson P, Markowetz F, Murphy L, Ellis I, Purushotham A, Børresen-Dale AL, Brenton JD, Tavaré S, Caldas C, Aparicio S. Nature. 2012 Apr 18;486(7403):346-52. PMID: 22522925; PMCID: PMC3440846.
Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Shah SP, Morin RD, Khattra J, Prentice L, Pugh T, Burleigh A, Delaney A, Gelmon K, Guliany R, Senz J, Steidl C, Holt RA, Jones S, Sun M, Leung G, Moore R, Severson T, Taylor GA, Teschendorff AE, Tse K, Turashvili G, Varhol R, Warren RL, Watson P, Zhao Y, Caldas C, Huntsman D, Hirst M, Marra MA, Aparicio S. Nature. 2009 Oct 8;461(7265):809-13.PMID: 19812674.
Spatio-temporal evolution of ovarian cancer at single cell resolution
McPherson et al. Nat Genetics 2016 ; Zhang et al. Cell 2018
Mutational processes in cancers of genomic instability
Wang et al. Nat Genetics 2017 ; Funnell et al. PLoS Comp Bio 2019
Malignant-immune cell interactions in the tumor microenvironment
Zhang et al. Cell 2018 ; Zhang et al. Nature Methods 2019
IMAXT: Imaging and Molecular Annotation of Xenografts and Tumors – in this Cancer Research UK Grand Challenge project, scientists aim to build a 3D tumour that can be studied using virtual reality and which shows every single different type of cell in the tumour
Computational methods development in the areas of single cell transcriptomics, cancer phylogenetics and cancer evolution
Campbell et al. Genome Biology 2019 ; Zhang et al. Nature Methods 2019 ; Eirew et al. Nature 2015 ; Roth et al. Nature Methods 2014 ; Roth et al. Nature Methods 2016 ; Laks et al. biorxiv
Multi-modal integration of data across radiology and pathology images, genomics, clinical phenotype and laboratory medicine
Please visit Dr. Shah’s faculty page, PubMed or Google Scholar for more publications.
