• Researcher Profile

    Laura MacConaill, PhD

    Laura MacConaill, PhD
    Principal Research Scientist, Harvard Medical School

    Scientific Director, Personalized Cancer Medicine Partnership
    Scientific Director, Center for Cancer Genome Discovery

    Office phone: 617-582-7754
    Fax: 617-394-2797
    Email: Laura_Macconaill@dfci.harvard.edu
    Website: www.cancergenomediscovery.org

    Preferred contact method: email

    Research Department

    Medical Oncology

    Area of Research

    Center for Cancer Genome Discovery Personalized Cancer Medicine Partnership

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Dana 1539
    Boston, MA 02215


    Dr. MacConaill is the Scientific Director of the Center for Cancer Genome Discovery (CCGD) at Dana-Farber Cancer Institute, and the Scientific Director of the Personalized Cancer Medicine Partnership (PCMP), a collaborative venture between Brigham and Womens Hospital and Dana-Farber Cancer Institute. She is a Principal Research Scientist at the Dana-Farber, Harvard Medical School, and an affiliate member of the Broad Institute of Harvard and MIT.

    Dr. MacConaill received her BSc in Microbiology in 1998 and her PhD in Molecular Biology from the National University of Ireland, Cork, in 2003. She conducted her postdoctoral studies with Dr. Matthew Meyerson at the Dana-Farber Cancer Institute, and joined the Center for Cancer Genome Discovery in 2006.

    As the Scientific Director of CCGD, Dr. MacConaill leads the Center in developing new technologies for the analysis of cancer genomes and to provide access to these technologies to investigators at Dana-Farber Cancer Institute, the Dana-Farber/Harvard Cancer Center, Harvard Medical School, the Massachusetts Institute of Technology, and other partnerships nationally and internationally. The CCGD also works at the forefront of translational cancer technologies and applications, transferring cutting-edge technologies to the clinical setting of PCMP to guide patient treatment options.


    Center for Cancer Genome Discovery Personalized Cancer Medicine Partnership

    The overall mission of the CCGD is to develop new technologies for the analysis of cancer genomes and to provide access to these technologies to investigators at Dana-Farber Cancer Institute, the Dana-Farber/Harvard Cancer Center, Harvard Medical School and the Massachusetts Institute of Technology. In this latter role, CCGD participates in the design, execution and analysis of both single gene and whole genome focused projects. More specifically, we have engaged in projects focused on the discovery of genomic alterations that contribute to human cancer, the evaluation of the clinical significance of these alterations in the setting of experimental therapeutic trials and the identification of approaches to identify such mutations retrospectively and prospectively in cancer patients.

    In collaboration with several groups in Medical Oncology, we have pioneered the development of a standard genotyping technology for the purpose of somatic mutation profiling of oncogenes and tumor suppressor genes in various cancers. For several years, members of CCGD have optimized this mass-spectrometric based genotyping to profile archival (i.e. formalin-fixed, paraffin-embedded) tissue samples (MacConaill et al., 2009). We have also developed mass-spec genotyping to look at other types of alterations that cause cancers- copy number changes, epigenetic modifications such as methylation of genes, as well as optimizing the technology to look at very subtle differences in gene expression in a quantitative manner.

    The CCGD, has completed over 70 projects with scientists and clinicians in the Boston area and beyond. We currently have active collaborations with England, Australia and Germany, in addition to many local and national projects; several of which have yielded high-profile and groundbreaking data (Min et al., 2010 Nature Medicine; Ahmadiyeh et al., 2010 PNAS; Badalian-Very et al., 2010 Blood). The CCGD and a program in Pediatric Low-Grade Astrocytomas directed by Mark Kieran and Charles Stiles in the Neuro-Oncology Program at DFCI have worked closely to identify druggable alterations in pediatric LGAs. Our work has set the stage for CLIA-certified assays on the activated BRAF oncoprotein that is found in a subset of pediatric LGAs.

    The CCGD continues to work at the forefront of translational cancer technologies and applications. In a joint venture between Dana-Farber and Brigham and Women's Hospital, the CCGD technologies are translated in a clinical setting, the The Personalized Cancer Medicine Partnership (PCMP). The mission of the PCMP is to advance translational and personalized cancer medicine by implementing tumor genomic profiling on all cancer patients treated at these institutions. PCMP will employ state-of-the art technology to generate a detailed profile of key "druggable" or otherwise "actionable" cancer genomic alterations in a CLIA-approved and "real-time" process to facilitate rapid clinical application. These cancer genomic profiles with be used to guide patient treatment and/or stratification for clinical trials of novel anticancer agents.

    Select Publications

    • MacConaill, L.E., C. O’Mahony, C. Dunne, C. Stanton, J.K. Collins, D. van Sinderen, P. Ross, and G.F. Fitzgerald. 2000. Analysis and application of probiotic bacteria. Int. J. Dairy Technol.  53:173.
    • MacConaill, L.E., D. van Sinderen, and G.F. Fitzgerald. 2002. Genetic organization of adaptive responses in Bifidobacterium. I. J. Ag. Food Res. 41:152.
    • MacConaill, L.E., D. Butler, M. O’Connell-Motherway, G.F. Fitzgerald, and D. van Sinderen. 2003. Identification of two-component regulatory systems in Bifidobacterium infantis by functional complementation and degenerate PCR approaches. Appl. Environ. Microbiol. 69(7):4219-4226.
    • MacConaill, L.E., G.F. Fitzgerald, and D. van Sinderen. 2003. Investigation of protein export in Bifidobacterium breve UCC 2003. Appl. Environ. Microbiol. 69(12):6994-7001.
    • MacConaill, L.E., C.M. Hughes, O. Rozenblatt-Rosen, S. Nannepaga, and M. Meyerson. 2006. Phosphorylation of the menin tumor suppressor protein on serine 543 and serine 583. Mol Cancer Res. 4(10):793-801.
    • MacConaill, L.E., M.A. Aldred, X. Lu and T. LaFramboise. 2007. Toward accurate high-throughput SNP genotyping in the presence of inherited copy number variation. BMC Genomics. 8:211. 
    • Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, Wang M, Feng W, Zander T, MacConaill L.E., Lee JC, …. Sellers WR, Meyerson M, Garraway LA. 2007. High-throughput oncogene mutation profiling in human cancer. Nat Genet. 39(3):347-351.
    • Nikolsky Y., E. Sviridov, J. Yao, D. Dosymbekov, V. Ustyansky, V. Kaznacheev, Z. Dezso, L. Mulvey, L. E. MacConaill, W. Winckler, T. Serebryiskaya, T. Nikolskaya and K. Polyak. 2008. Genome-Wide Functional Synergy between Amplified and Mutated Genes in Human Breast Cancer. Cancer Res. 68: 9532-9540.
    • MacConaill, L., and M. Meyerson. 2008. Adding pathogens by genomic subtraction. Nat Genet. 40:380-382.
    • MacConaill LE, Campbell CD, Kehoe SM, Bass AJ, Hatton C, et al. 2009. Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples. PLoS ONE 4(11): e7887.
    • Emery CM, Vijayendran KG, Zipser MC, Sawyer AM, Niu L, Kim JJ, Hatton C, Chopra R, Oberholzer PA, Karpova MB, MacConaill LE, Zhang J, Gray NS, Sellers WR, Dummer R, Garraway LA. 2009. MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci U S A. 106(48):20411.
    • Rhodes J., Amsterdam A, Sanda T, Moreau LA, McKenna K, Heinrichs S, Ganem NJ, Ho KW, Neuberg DS, Johnston A, Ahn Y, Kutok JL, Hromas R, Wray J, Lee C, Murphy C, Radke I, Downing JR, Fleming MD, MacConaill LE, Amatruda JF, Gutierrez A, Galinsky I, Stone RM, Ross EA, Pellman DS, Kanki JP, Look AT. 2009. Emi1 Maintains Genomic Integrity during Zebrafish Embryogenesis and Cooperates with p53 in Tumor Suppression. Mol Cell Biol. 29(21):5911.
    • MacConaill L.E. and L.A. Garraway. 2010. Clinical Implications of the Cancer Genome. Journal of Clinical Oncology, (Epub Oct 25). 
    • Miron A, Varadi M, Carrasco D, Li H, Luongo L, Kim HJ, Park SY, Cho EY, Lewis G, Kehoe S, Iglehart JD, Dillon D, Allred C, MacConaill L, Gelman R, Polyak K. 2010. “PIK3CA mutations in in situ and invasive breast carcinomas,” Cancer Research, 70(14):5674-8.
    • Badalian-Very G, Vergilio J, Degar B.A., Brandner B, Calicchio ML, Kuo FC, Ligon AH, Stevenson KE, Kehoe SM, MacConaill LE, Garraway LA, Hahn WC, Meyerson M, Fleming MD, and B.J. Rollins. 2010. Recurrent BRAF Mutations in Langerhans Cell Histiocytosis. Blood. 116(11):1919-23.
    • Ahmadiyeh N, Pomerantz M., Grisanzio C, Herman P, Jia L, Almendro V, Hansen He H, Brown M, Liu XS, Davis M, Caswell JL, Beckwith CA, Hills A, MacConaill L, Coetzee GA, Regan MM, Freedman ML., 2010. 8q24 prostate, breast, and colon cancer risk loci show tissue-specific long range interaction with MYC. Proc Natl Acad Sci U S A. 107(21):9742-6.
    • Søndergaard JN, Nazarian R, Wang Q, Guo D, … MacConaill LE, ....and A. Ribas. 2010. Differential Sensitivity of Melanoma Cell Lines with BRAF V600E Mutation to the Specific B-Raf Inhibitor PLX4032. Journal of Translational Medicine. 8:39.
    • Min J, Zaslavsky A, Fedele G, McLaughlin SK, Reczek EE, De Raedt T, Guney I, Strochlic DE, MacConaill LE, Beroukhim R, Bronson RT, Ryeom S, Hahn WC, Loda M, Cichowski K. 2010. An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappaB. Nat Med. Feb 14.
    • Wagle N, Berger MF, Davis MJ, Blumenstiel B, deFelice M, Pochanard P, Ducar M, Van Hummelen P, MacConaill LE, Hahn WC, Meyerson M, Gabriel SB, and LA Garraway. 2011.  High-Throughput Detection of Actionable Genomic Alterations in Clinical Tumor Samples by Targeted, Massively Parallel Sequencing. Cancer Discovery. 2(1):82-93.
    • Choy E, Hornicek F, MacConaill L, Harmon D, Tariq Z, Garraway L, Duan Z. 2011. High-throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide-3-kinase and other oncogenes. Cancer. 118(11):2905-14.
    • MacConaill LE, Van Hummelen P, Meyerson M, Hahn WC. 2011. Clinical implementation of comprehensive strategies to characterize cancer genomes: opportunities and challenges. Cancer Discov. 1(4):297.
    • Qin W, Bajaj V, Malinowska I, Lu X, MacConaill L, Wu C-L, and DJ Kwiatkowski. 2011. Angiomyolipoma Have Common Mutations in TSC2 but No Other Common Genetic Events. PLoS ONE 6(9): e24919.
    • Matulonis UA, Hirsch M, Palescandolo E, Kim E, Liu J, van Hummelen P, MacConaill L, Drapkin R, Hahn WC. 2011. High throughput interrogation of somatic mutations in high grade serous cancer of the ovary. PLoS One. 6(9):e24433.
    • Tian Y, Rich BE, Vena N, Craig JM, MacConaill LE, Rajaram V, Goldman S, Taha H, Mahmoud M, Ozek M, Sav A, Longtine JA, Lindeman NI, Garraway LA, Ligon AH, Stiles CD, Santagata S, Chan JA, Kieran MW, Ligon KL. 2011. Detection of KIAA1549-BRAF Fusion Transcripts in Formalin-Fixed Paraffin-Embedded Pediatric Low-Grade Gliomas. J Mol Diagn. 2011 Aug 29.
    • Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A, Pochanard P, Kehoe SM, Johannessen CM, Macconaill LE, Hahn WC, Meyerson M, Garraway LA. 2011. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol. 29(22):3085-96. 
    • Deshpande V, Nduaguba A, Zimmerman SM, Kehoe SM, Macconaill LE, Lauwers GY, Ferrone C, Bardeesy N, Zhu AX, Hezel AF. 2011. Mutational profiling reveals PIK3CA mutations in gallbladder carcinoma. BMC Cancer.11:60.
    • Kiessling MK, Oberholzer PA, Mondal C, Karpova MB, Zipser MC, Lin WM, Girardi M, Macconaill LE, Kehoe SM, Hatton C, French LE, Garraway LA, Polier G, Süss D, Klemke CD, Krammer PH, Gülow K, Dummer R. 2011. High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK signaling cascade. Blood. 117(8):2433-40.
    • MacConaill LE. 2012.  Advancing Personalized Cancer Medicine in Lung Cancer. Archives of Pathology & Laboratory Medicine. 136(10):1210-1216
    • Kieran MW, Roberts CW, Chi SN, Ligon KL, Rich BE, Macconaill LE, Garraway LA, Biegel JA. 2012. Absence of oncogenic canonical pathway mutations in aggressive pediatric rhabdoid tumors. Pediatr Blood Cancer. 59(7):1155-7.
    • Daniels AB, Lee JE, Macconaill LE, Palescandolo E, Van Hummelen P, Adams SM, Deangelis MM, Hahn WC, Gragoudas ES, Harbour JW, Garraway LA, Kim IK.2012. High throughput mass spectrometry-based mutation profiling of primary uveal melanoma. Invest Ophthalmol Vis Sci. Sep 13.
    • Maeng CH, Lee J, van Hummelen P, Park SH, Palescandolo E, Jang J, Park HY, Kang SY, Macconaill L, Kim KM, Shim YM. 2012. High-Throughput Genotyping in Metastatic Esophageal Squamous Cell Carcinoma Identifies Phosphoinositide-3-Kinase and BRAF Mutations. PLoS One.7(8):e41655.
    • Lovejoy CA, Li W, Reisenweber S, Thongthip S, Bruno J, de Lange T, De S, Petrini JH, Sung PA, Jasin M, Rosenbluh J, Zwang Y, Weir BA, Hatton C, Ivanova E, Macconaill L, Hanna M, Hahn WC, Lue NF, Reddel RR, Jiao Y, Kinzler K, Vogelstein B, Papadopoulos N, Meeker AK; for the ALT Starr Cancer Consortium. 2012. Loss of ATRX, Genome Instability, and an Altered DNA Damage Response Are Hallmarks of the Alternative Lengthening of Telomeres Pathway. PLoS Genet. Jul;8(7):e1002772.
    • Lee J, van Hummelen P, Go C, Palescandolo E, Jang J, Park HY, Kang SY, Park JO, Kang WK, Macconaill L, Kim KM. 2012. High-throughput mutation profiling identifies frequent somatic mutations in advanced gastric adenocarcinoma. PLoS One. 2012;7(6):e38892. 
    • Brown JR, Hanna M, Tesar B, Werner L, Pochet N, Asara JM, Wang YE, Dal Cin P, Fernandes SM, Thompson C, MacConaill L, Wu CJ, Van de Peer Y, Correll M, Regev A, Neuberg D, Freedman AS. 2012. Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia. Clin Cancer Res. 18(14):3791-802.
    • Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim, S…… MacConaill L, …… Meyerson M, Golub TR, Morrissey MP, Sellers WR, Schlegel R, and LA Garraway. 2012. The Cancer Cell Line Encyclopedia enables predictive modeling of anticancer drug sensitivity. Nature. 483(7391):603-7.
    • Brown JR, M Hanna, B Tesar, N Pochet, A Vartanov, SM Fernandes, L Werner, M Ash, CA Roden, L MacConaill, U Hainz, J Longtine, YE Wang, M Correll, Y Van De Peer, A Regev, C Wu, D Neuberg, AS Freedman. Germline Copy Number Variation Associated with Mendelian Inheritance of CLL in Two Families. 2012. Leukemia. 26(7):1710-3.
    • Williams, D.R., Kontos, E.Z., Viswanath, K. Haas, J.S., Lathan, C.S., MacConaill, L.E., Chen, J., Ayanian, J.Z. 2012. Integrating multiple social statuses in health disparities research: the case of lung cancer. Health Services Research. 47(3 Pt 2):1255-77.
    • Oberholzer PA, Kee D, Dziunycz P, Sucker A, Kamsukom N, Jones R, Roden C, Chalk CJ, Ardlie K, Palescandolo E, Piris A, MacConaill LE, Robert C, Hofbauer GF, McArthur GA, Schadendorf D, Garraway LA. 2012. RAS Mutations Are Associated With the Development of Cutaneous Squamous Cell Tumors in Patients Treated With RAF Inhibitors. J Clin Oncol. 30(3):316-21.
    • Grill J, Puget S, Andreiuolo F, Philippe C, MacConaill L, Kieran MW. 2012. Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma. Pediatr Blood Cancer.  58(4):489-91.
    • Brastianos PK, Horowitz PM, Santagata S, Jones RT, McKenna A, Getz G, Ligon KL, Palescandolo E, Van Hummelen P, Ducar MD, Raza A, Sunkavalli A, MacConaill LE, Stemmer-Rachamimov AO, Louis DN, Hahn WC, Dunn IF, Beroukhim R. 2013. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet. Jan 20.