Photo of Michael S. Lawrence,  PhD

Michael S. Lawrence, PhD

Massachusetts General Hospital

Massachusetts General Hospital

Michael S. Lawrence, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Pathology, Harvard Medical School
  • Assistant Geneticist, Center for Cancer Research, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Cancer results from alterations to DNA that lead to the activation of oncogenes or the inactivation of tumor suppressors. The Lawrence Laboratory focuses on understanding the many ways this can happen, using computation as a powerful microscope to study the processes of DNA damage and repair, gene expression and genome replication, and cancer driver genes. Over our lifetimes, DNA slowly accumulates mutations due to environmental toxins and radiation, as well as from naturally occurring copying errors. The vast majority of mutations have little or no effect on a cell, but out of all possible mutations, a few may hit exactly the right place in the genome where they can act as a "driver mutation," pushing the cell toward aggressive growth and tumor formation. Sequencing the DNA in a tumor reveals not only its driver mutations, but also all the other "passenger mutations" that were present in the tumor-initiating cell. We seek insights about cancer from both driver and passenger mutations.

Publications

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  • Dagogo-Jack I, Yoda S, Lennerz JK, Langenbucher A, Lin JJ, Rooney MM, Prutisto-Chang K, Oh A, Adams NA, Yeap BY, Chin E, Do A, Marble HD, Stevens SE, Digumarthy SR, Saxena A, Nagy RJ, Benes CH, Azzoli CG, Lawrence MS, Gainor JF, Shaw AT, Hata AN. MET Alterations are a Recurring and Actionable Resistance Mechanism in ALK-Positive Lung Cancer. Clin Cancer Res 2020. PubMed
  • Lee S, Micalizzi D, Truesdell SS, Bukhari SIA, Boukhali M, Lombardi-Story J, Kato Y, Choo MK, Dey-Guha I, Ji F, Nicholson BT, Myers DT, Lee D, Mazzola MA, Raheja R, Langenbucher A, Haradhvala NJ, Lawrence MS, Gandhi R, Tiedje C, Diaz-Muñoz MD, Sweetser DA, Sadreyev R, Sykes D, Haas W, Haber DA, Maheswaran S, Vasudevan S. A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells. Genome Biol 2020; 21:33. PubMed
  • Reyna MA, Haan D, Paczkowska M, Verbeke LPC, Vazquez M, Kahraman A, Pulido-Tamayo S, Barenboim J, Wadi L, Dhingra P, Shrestha R, Getz G, Lawrence MS, Pedersen JS, Rubin MA, Wheeler DA, Brunak S, Izarzugaza JMG, Khurana E, Marchal K, von Mering C, Sahinalp SC, Valencia A, , Reimand J, Stuart JM, Raphael BJ, . Pathway and network analysis of more than 2500 whole cancer genomes. Nat Commun 2020; 11:729. PubMed
  • Karaayvaz-Yildirim M, Silberman RE, Langenbucher A, Saladi SV, Ross KN, Zarcaro E, Desmond A, Yildirim M, Vivekanandan V, Ravichandran H, Mylavagnanam R, Specht MC, Ramaswamy S, Lawrence M, Amon A, Ellisen LW. Aneuploidy and a deregulated DNA damage response suggest haploinsufficiency in breast tissues of mutation carriers. Sci Adv 2020; 6:eaay2611. PubMed
  • Porter RL, Magnus NKC, Thapar V, Morris R, Szabolcs A, Neyaz A, Kulkarni AS, Tai E, Chougule A, Hillis A, Golczer G, Guo H, Yamada T, Kurokawa T, Yashaswini C, Ligorio M, Vo KD, Nieman L, Liss AS, Deshpande V, Lawrence MS, Maheswaran S, Fernandez-Del Castillo C, Hong TS, Ryan DP, O'Dwyer PJ, Drebin JA, Ferrone CR, Haber DA, Ting DT. Epithelial to mesenchymal plasticity and differential response to therapies in pancreatic ductal adenocarcinoma. Proc Natl Acad Sci U S A 2020. PubMed
  • Clarke TL, Tang R, Chakraborty D, Van Rechem C, Ji F, Mishra S, Ma A, Kaniskan HU, Jin J, Lawrence MS, Sadreyev RI, Whetstine JR. Histone Lysine Methylation Dynamics Control EGFR DNA Copy Number Amplification. 2019. PubMed
  • Bai B, Vodák D, Nakken S, Wise JF, Blaker YN, Lingjærde OC, Brodtkorb M, Hilden V, Trøen G, Lorenz S, Lawrence MS, Myklebost O, Meza-Zepeda L, Beiske K, Hovig E, Smeland EB, Holte H, Myklebust JH. Deep Profiling of Genetic Aberrations and Clonal Evolution in Follicular Lymphoma. Blood 2019; 134:20. PubMed
  • Farago AF, Yeap BY, Stanzione M, Hung YP, Heist RS, Marcoux JP, Zhong J, Rangachari D, Barbie DA, Phat S, Myers DT, Morris R, Kem M, Dubash TD, Kennedy EA, Digumarthy SR, Sequist LV, Hata AN, Maheswaran S, Haber DA, Lawrence MS, Shaw AT, Mino-Kenudson M, Dyson NJ, Drapkin BJ. Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer. 2019; 9:1372-1387. PubMed
  • Kolesnikova S, Srb P, Vrzal L, Lawrence MS, Veverka V, Curtis EA. GTP-Dependent Formation of Multimeric G-Quadruplexes. ACS Chem Biol 2019; 14:1951-1963. PubMed
  • Hess JM, Bernards A, Kim J, Miller M, Taylor-Weiner A, Haradhvala NJ, Lawrence MS, Getz G. Passenger Hotspot Mutations in Cancer. Cancer Cell 2019; 36:288-301.e14. PubMed
  • Sakhtemani R, Senevirathne V, Stewart J, Perera MLW, Pique-Regi R, Lawrence MS, Bhagwat AS. Genome-wide mapping of regions preferentially targeted by the human DNA-cytosine deaminase APOBEC3A using uracil-DNA pulldown and sequencing. J Biol Chem 2019. PubMed
  • Ghandi M, Huang FW, Jané-Valbuena J, Kryukov GV, Lo CC, McDonald ER, Barretina J, Gelfand ET, Bielski CM, Li H, Hu K, Andreev-Drakhlin AY, Kim J, Hess JM, Haas BJ, Aguet F, Weir BA, Rothberg MV, Paolella BR, Lawrence MS, Akbani R, Lu Y, Tiv HL, Gokhale PC, de Weck A, Mansour AA, Oh C, Shih J, Hadi K, Rosen Y, Bistline J, Venkatesan K, Reddy A, Sonkin D, Liu M, Lehar J, Korn JM, Porter DA, Jones MD, Golji J, Caponigro G, Taylor JE, Dunning CM, Creech AL, Warren AC, McFarland JM, Zamanighomi M, Kauffmann A, Stransky N, Imielinski M, Maruvka YE, Cherniack AD, Tsherniak A, Vazquez F, Jaffe JD, Lane AA, Weinstock DM, Johannessen CM, Morrissey MP, Stegmeier F, Schlegel R, Hahn WC, Getz G, Mills GB, Boehm JS, Golub TR, Garraway LA, Sellers WR. Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature 2019; 569:503-508. PubMed
  • Sanidas I, Morris R, Fella KA, Rumde PH, Boukhali M, Tai EC, Ting DT, Lawrence MS, Haas W, Dyson NJ. A Code of Mono-phosphorylation Modulates the Function of RB. Mol Cell 2019; 73:985-1000.e6. PubMed
  • Buisson R, Langenbucher A, Bowen D, Kwan EE, Benes CH, Zou L, Lawrence MS. Passenger hotspot mutations in cancer driven by APOBEC3A and mesoscale genomic features. Science 2019. PubMed
  • Medford AJ, Dubash TD, Juric D, Spring L, Niemierko A, Vidula N, Peppercorn J, Isakoff S, Reeves BA, LiCausi JA, Wesley B, Malvarosa G, Yuen M, Wittner BS, Lawrence MS, Iafrate AJ, Ellisen L, Moy B, Toner M, Maheswaran S, Haber DA, Bardia A. Blood-based monitoring identifies acquired and targetable driver mutations in endocrine-resistant metastatic breast cancer. NPJ Precis Oncol 2019; 3:18. PubMed
  • Wise JF, Lawrence MS. Huge whole-genome study of human metastatic cancers. Nature 2019; 575:60-61. PubMed
  • Mishra S, Van Rechem C, Pal S, Clarke TL, Chakraborty D, Mahan SD, Black JC, Lawrence MS, Daniels DL, Whetstine JR. Cross-talk between Lysine-Modifying Enzymes Controls Site-Specific DNA Amplifications. Cell 2018; 174:803-817.e16. PubMed
  • Yoda S, Lin JJ, Lawrence MS, Burke BJ, Friboulet L, Langenbucher A, Dardaei L, Prutisto-Chang K, Dagogo-Jack I, Timofeevski S, Hubbeling H, Gainor JF, Ferris LA, Riley AK, Kattermann KE, Timonina D, Heist RS, Iafrate AJ, Benes CH, Lennerz JK, Mino-Kenudson M, Engelman JA, Johnson TW, Hata AN, Shaw AT. Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound Mutations in ALK-Positive Lung Cancer. 2018; 8:714-729. PubMed
  • Hoadley KA, Yau C, Hinoue T, Wolf DM, Lazar AJ, Drill E, Shen R, Taylor AM, Cherniack AD, Thorsson V, Akbani R, Bowlby R, Wong CK, Wiznerowicz M, Sanchez-Vega F, Robertson AG, Schneider BG, Lawrence MS, Noushmehr H, Malta TM, , Stuart JM, Benz CC, Laird PW. Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer. Cell 2018; 173:291-304.e6. PubMed
  • Dardaei L, Wang HQ, Singh M, Fordjour P, Shaw KX, Yoda S, Kerr G, Yu K, Liang J, Cao Y, Chen Y, Lawrence MS, Langenbucher A, Gainor JF, Friboulet L, Dagogo-Jack I, Myers DT, Labrot E, Ruddy D, Parks M, Lee D, DiCecca RH, Moody S, Hao H, Mohseni M, LaMarche M, Williams J, Hoffmaster K, Caponigro G, Shaw AT, Hata AN, Benes CH, Li F, Engelman JA. SHP2 inhibition restores sensitivity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors. Nat Med 2018. PubMed
  • Buisson R, Lawrence MS, Benes CH, Zou L. APOBEC3A and APOBEC3B Activities Render Cancer Cells Susceptible to ATR Inhibition. Cancer Res 2017; 77:4567-4578. PubMed
  • Haradhvala NJ, Polak P, Stojanov P, Covington KR, Shinbrot E, Hess JM, Rheinbay E, Kim J, Maruvka YE, Braunstein LZ, Kamburov A, Hanawalt PC, Wheeler DA, Koren A, Lawrence MS, Getz G. Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair. Cell 2016; 164:538-49. PubMed
  • Švehlová K, Lawrence MS, Bednárová L, Curtis EA. Altered biochemical specificity of G-quadruplexes with mutated tetrads. Nucleic Acids Res 2018; 44:10789-10803. PubMed
  • Helman E, Lawrence MS, Stewart C, Sougnez C, Getz G, Meyerson M. Somatic retrotransposition in human cancer revealed by whole-genome and exome sequencing. Genome Res 2014. PubMed
  • Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, Meyerson M, Gabriel SB, Lander ES, Getz G. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 2014; 505:495-501. PubMed
  • Lohr JG, Stojanov P, Carter SL, Cruz-Gordillo P, Lawrence MS, Auclair D, Sougnez C, Knoechel B, Gould J, Saksena G, Cibulskis K, McKenna A, Chapman MA, Straussman R, Levy J, Perkins LM, Keats JJ, Schumacher SE, Rosenberg M, , Getz G, Golub TR. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell 2014; 25:91-101. PubMed
  • Roberts SA, Lawrence MS, Klimczak LJ, Grimm SA, Fargo D, Stojanov P, Kiezun A, Kryukov GV, Carter SL, Saksena G, Harris S, Shah RR, Resnick MA, Getz G, Gordenin DA. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet 2013; 45:970-6. PubMed
  • 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; 499:214-8. PubMed
  • Cibulskis K, Lawrence MS, Carter SL, Sivachenko A, Jaffe D, Sougnez C, Gabriel S, Meyerson M, Lander ES, Getz G. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol 2013; 31:213-9. PubMed
  • 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; 152:714-26. PubMed
  • Drier Y, Lawrence MS, Carter SL, Stewart C, Gabriel SB, Lander ES, Meyerson M, Beroukhim R, Getz G. Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability. Genome Res 2013. PubMed
  • Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet JP, Ahmann GJ, Adli M, Anderson KC, Ardlie KG, Auclair D, Baker A, Bergsagel PL, Bernstein BE, Drier Y, Fonseca R, Gabriel SB, Hofmeister CC, Jagannath S, Jakubowiak AJ, Krishnan A, Levy J, Liefeld T, Lonial S, Mahan S, Mfuko B, Monti S, Perkins LM, Onofrio R, Pugh TJ, Rajkumar SV, Ramos AH, Siegel DS, Sivachenko A, Stewart AK, Trudel S, Vij R, Voet D, Winckler W, Zimmerman T, Carpten J, Trent J, Hahn WC, Garraway LA, Meyerson M, Lander ES, Getz G, Golub TR. Initial genome sequencing and analysis of multiple myeloma. Nature 2011; 471:467-72. PubMed
  • Lawrence MS, Phillips KJ, Liu DR. Supercharging proteins can impart unusual resilience. J Am Chem Soc 2017; 129:10110-2. PubMed
  • Lawrence MS, Bartel DP. New ligase-derived RNA polymerase ribozymes. RNA 2014; 11:1173-80. PubMed
  • Lawrence MS, Bartel DP. Processivity of ribozyme-catalyzed RNA polymerization. Biochemistry 2007; 42:8748-55. PubMed
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