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Genetics Faculty

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Thomas LaFramboise
Associate Professor
Ph.D. Training Faculty
Department of Genetics
School of Medicine
Case Western Reserve University
Biomedical Research Building 625
2109 Adelbert Road
Cleveland, Ohio 44106-4955
Tel: (216) 368-0150
Fax: (216) 368-3432
E-mail: thomas.laframboise@case.edu


About Thomas LaFramboise

Tom LaFramboise earned his B.S. from the University of Michigan at Ann Arbor and his Ph.D. from the University of Illinois at Urbana-Champaign, both degrees being in theoretical mathematics. Subsequently, he spent several years as Assistant and Associate Professor in the mathematics department at Marietta College in Marietta, OH. In 2002, Tom decided to retrain in biostatistics, earning a Master's degree at the Harvard School of Public Health, which led to a postdoctoral position in cancer genomics in the laboratory of Matthew Meyerson at the Dana-Farber Cancer Institute and the Broad Institute of Harvard/MIT. He joined the department in August 2006.


Research

Broadly, Dr. LaFramboise is interested in developing and applying computational tools to identify molecular variants - both inherited and somatic - that contribute to cancer and related diseases in humans. His postdoctoral work centered on the statistical modeling of data from SNP microarrays to detect DNA copy number changes in tumors, and he has written a number of R software packages designed to draw biological inferences from genomic data. His group is currently developing and applying methods to mine high-dimensional data sets, with the goal of generating hypotheses regarding gene function in tumor initiation, progression, and metastasis. We then test these hypotheses in the laboratory using human cancer cells.


Selected Publications

DB2: a probabilistic approach for accurate detection of tandem duplication breakpoints using paired-end reads.
Yavas G, Koyuturk M, Gould MP, McMahon S, Laframboise T
BMC Genomics (2014);15(1):175
See PubMed abstract

Mutational patterns in the breast cancer mitochondrial genome, with clinical correlates.
McMahon S, Laframboise T
Carcinogenesis (2014);:
See PubMed abstract

Calling amplified haplotypes in next generation tumor sequence data.
Dewal N, Hu Y, Freedman ML, Laframboise T, Pe'er I
Genome Res (2011);:
See PubMed abstract

Losing Balance: Hardy-Weinberg Disequilibrium as a Marker for Recurrent Loss-of-Heterozygosity in Cancer.
Wilkins K, Laframboise T
Hum Mol Genet (2011);:
See PubMed abstract

Comparative analysis of algorithms for next-generation sequencing read alignment.
Ruffalo M, LaFramboise T, Koyuturk M
Bioinformatics (2011);:
See PubMed abstract

A 32 kb Critical Region Excluding Y402H in CFH Mediates Risk for Age-Related Macular Degeneration.
Sivakumaran TA, Igo RP, Kidd JM, Itsara A, Kopplin LJ, Chen W, Hagstrom SA, Peachey NS, Francis PJ, Klein ML, Chew EY, Ramprasad VL, Tay WT, Mitchell P, Seielstad M, Stambolian DE, Edwards AO, Lee KE, Leontiev DV, Jun G, Wang Y, Tian L, Qiu F, Henning AK, Laframboise T, Sen P, Aarthi M, George R, Raman R, Das MK, Vijaya L, Kumaramanickavel G, Wong TY, Swaroop A, Abecasis GR, Klein R, Klein BE, Nickerson DA, Eichler EE, Iyengar SK
PLoS One (2011);6(10):e25598
See PubMed abstract

Allelic selection of amplicons in glioblastoma revealed by combining somatic and germline analysis.
Laframboise T, Dewal N, Wilkins K, Pe'er I, Freedman ML
PLoS Genet (2010);6(9):
See PubMed abstract

CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression.
Schnetz MP, Handoko L, Akhtar-Zaidi B, Bartels CF, Pereira CF, Fisher AG, Adams DJ, Flicek P, Crawford GE, Laframboise T, Tesar P, Wei CL, Scacheri PC
PLoS Genet (2010);6(7):e1001023
See PubMed abstract

Cokgen: a software for the identification of rare copy number variation from SNP microarrays.
Yavaş G, Koyutürk M, Ozsoyoğlu M, Gould MP, Laframboise T
Pac Symp Biocomput (2010);:371-82
See PubMed abstract

Dual specificity phosphatase 6 (DUSP6) is an ETS-regulated negative feedback mediator of oncogenic ERK-signaling in lung cancer cells.
Zhang Z, Kobayashi S, Borczuk AC, Leidner RS, Laframboise T, Levine AD, Halmos B
Carcinogenesis (2010);:
See PubMed abstract

Power to Detect Selective Allelic Amplification in Genome-wide Scans of Tumor Data.
Dewal N, Freedman ML, Laframboise T, Pe'er I
Bioinformatics (2009);:
See PubMed abstract

An Optimization Framework for Unsupervised Identification of Rare Copy Number Variation from SNP Array Data.
Yavas G, Koyuturk M, Ozsoyoglu M, Gould M, Laframboise T
Genome Biol (2009);10(10):R119
See PubMed abstract

Single nucleotide polymorphism arrays: a decade of biological, computational and technological advances.
LaFramboise T
Nucleic Acids Res (2009);37(13):4181-93
See PubMed abstract

Predicting drug susceptibility of non-small cell lung cancers based on genetic lesions.
Sos ML, Michel K, Zander T, Weiss J, Frommolt P, Peifer M, Li D, Ullrich R, Koker M, Fischer F, Shimamura T, Rauh D, Mermel C, Fischer S, Stückrath I, Heynck S, Beroukhim R, Lin W, Winckler W, Shah K, Laframboise T, Moriarty WF, Hanna M, Tolosi L, Rahnenführer J, Verhaak R, Chiang D, Getz G, Hellmich M, Wolf J, Girard L, Peyton M, Weir BA, Chen TH, Greulich H, Barretina J, Shapiro GI, Garraway LA, Gazdar AF, Minna JD, Meyerson M, Wong KK, Thomas RK
J Clin Invest (2009);:
See PubMed abstract

A flexible rank-based framework for detecting copy number aberrations from array data.
LaFramboise T, Winckler W, Thomas RK
Bioinformatics (2009);25(6):722-8
See PubMed abstract

Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns.
Schnetz MP, Bartels CF, Shastri K, Balasubramanian D, Zentner GE, Balaji R, Zhang X, Song L, Wang Z, Laframboise T, Crawford GE, Scacheri PC
Genome Res (2009);19(4):590-601
See PubMed abstract

The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3' mRNA processing factors.
Rozenblatt-Rosen O, Nagaike T, Francis JM, Kaneko S, Glatt KA, Hughes CM, Laframboise T, Manley JL, Meyerson M
Proc Natl Acad Sci U S A (2009);:
See PubMed abstract

SNP arrays in heterogeneous tissue: highly accurate collection of both germline and somatic genetic information from unpaired single tumor samples.
Assié G, LaFramboise T, Platzer P, Bertherat J, Stratakis CA, Eng C
Am J Hum Genet (2008);82(4):903-15
See PubMed abstract

Frequency of germline genomic homozygosity associated with cancer cases.
Assié G, LaFramboise T, Platzer P, Eng C
JAMA (2008);299(12):1437-45
See PubMed abstract

Epitope tagging of endogenous proteins for genome-wide ChIP-chip studies.
Zhang X, Guo C, Chen Y, Shulha HP, Schnetz MP, LaFramboise T, Bartels CF, Markowitz S, Weng Z, Scacheri PC, Wang Z
Nat Methods (2008);5(2):163-5
See PubMed abstract

Toward accurate high-throughput SNP genotyping in the presence of inherited copy number variation.
Macconaill LE, Aldred MA, Lu X, Laframboise T
BMC Genomics (2007);8(1):211
See PubMed abstract

High-throughput oncogene mutation profiling in human cancer
Thomas RK, Baker AC, DeBiasi RM, Winckler W, LaFramboise T, Lin WM, Feng W, Wang M, MacConnaill LE, Lee JC, Nicoletti R, Hatton C, Goyette M, Girard L, Majmudar K, Ziaugra L, Wong KK, Gabriel S, Beroukhim R, Peyton M, Barretina J, Dutt A, Emery C, Greulich H, Shah K, Sasaki H, Gazdar AF, Minna J, Armstrong SA, Mellinghoff IK, Hodi FS, Dranoff G, Mischel PS, Cloughesy TF, Nelson SF, Liau LM, Mertz K, Rubin MA, Moch H, Loda M, Catalona W, Fletcher J, Signoretti S, Kaye F, Anderson KC, Demetri GD, Dummer R, Wagner S, Herlyn M, Sellers WR, Meyerson M, Garraway LA
Nature Genetics (2007);(In Press)

The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ ERBB2 inhibitor HKI-272
Minami Y, Shimamura T, Shah K, LaFramboise T, Glatt KA, Liniker E, Borgman CL, Haringsma HJ, Feng W, Weir BA, Lowell AM, Lee JC, Wolf J, Shapiro GI, Wong KK, Meyerson M, Thomas RK
Oncogene (2007);(In Press)

A transforming MET mutation discovered in non-small cell lung cancer using microarray-based resequencing
Tengs T, Lee JC, Guillermo Paez J, Zhao X, LaFramboise T, Giannoukos G, Thomas RK
Cancer Lett (2006);239(2):227-33
See PubMed abstract

Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing
Thomas RK, Nickerson E, Simons JF, Janne PA, Tengs T, Yuza Y, Garraway LA, LaFramboise T, Lee JC, Shah K, O'neill K, Sasaki H, Lindeman N, Wong KK, Borras AM, Gutmann EJ, Dragnev KH, Debiasi R, Chen TH, Glatt KA, Greulich H, Desany B, Lubeski CK, Brockman W, Alvarez P, Hutchison SK, Leamon JH, Ronan MT, Turenchalk GS, Egholm M, Sellers WR, Rothberg JM, Meyerson M
Nat Med (2006);12(7):852-855
See PubMed abstract

PLASQ: A Generalized Linear Model-Based Procedure to Determine Allelic Dosage in Cancer Cells from SNP Array Data
LaFramboise T, Harrington D, Weir BA
Biostatistics (2006);
See PubMed abstract

Allele-specific amplification in cancer revealed by SNP array analysis
LaFramboise T, Weir BA, Zhao X, Beroukhim R, Li C, Harrington D, Sellers WR, Meyerson M.
PLoS Comput Biol (2005);1(6):e65
See PubMed abstract

Homozygous deletions and chromosome amplifications in human lung carcinomas revealed by single nucleotide polymorphism array analysis
Zhao, X., Weir, B., LaFramboise, T., Lin, M., Beroukhim, R., Garraway, L., Beheshti, J., Lee, J., Naoki, K., Chen, F., et al.
Cancer Research (2005);65: 5561 - 5570
See PubMed abstract

A graph-theoretic approach to testing associations between disparate sources of functional genomics data
Balasubramanian R, LaFramboise T, Scholtens D, Gentleman R.
Bioinformatics (2004);20:3353-62
See PubMed abstract

Genomic representations using concatenates of Type IIB restriction endonuclease digestion fragments
Tengs T, LaFramboise T, Den RB, Hayes DN, Zhang J, DebRoy S, Gentleman RC, O'Neill K, Birren B, Meyerson M.
Nucleic Acids Res (2004);32(15):e121
See PubMed abstract

Statistical analysis of genomic tag data
LaFramboise TL, Hayes DN, Tengs T.
Stat Appl Genet Mol Biol (2004);3(1):Article34
See PubMed abstract

Contributing author to Comprehensive Dictionary of Mathematics
CRC Press. (2001);