Todd Druley, M.D., Ph.D.

Associate Professor
Developmental Biology

Molecular Genetics and Genomics Program
Developmental, Regenerative and Stem Cell Biology Program
Human and Statistical Genetics Program

Research Abstract:

The Druley lab is focused on integrating computational and functional biology to characterize how rare individual germline variation influences the onset and outcome of pediatric cancer. The lab has two main objectives: 1) develop new genomic and computational methodology for characterizing genetic or epigenetic variation, and 2) apply these methods to translational questions in pediatric cancer. Computational analysis of infant leukemia has identified a pattern of germline variation that we are functionally testing in patient-specific iPSCs modified by CRISPR. We have developed error-corrected sequencing (ECS) that can identify clonal mutations in heterogeneous DNA samples as rare as 1:10,000 molecules. With this we are re-defining normal and leukemic clonal hematopoiesis in children and adults.

Selected Publications:

Young, A.L., Challen, G.A., Birmann, B.M., Druley, T.E. (2016) Clonal hematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults. Nat Commun. 2016 Aug 22;7:12484. doi: 10.1038/ncomms12484.

Druley, T.E. (2016) The relative contributions of germline variation, epimutation and somatic mutation to paediatric leukemia predisposition. EMJ Hematol, 4(1), 110-116.

Young, A.L., Wong, T.N., Hughes, A.E.O., Heath, S.E., Ley, T.J., Link, D.C., Druley, T.E. (2015) Quantifying ultra-rare pre-leukemic clones via targeted error-corrected sequencing. Leukemia, 2015 Feb 3. doi: 10.1038/leu.2015.17. PMID: 25644247

Wong, T.N.*, Ramsingh, G.*, Young, A.L.*, Miller, C.A., Touma, W., Welch, J.S., Lamprecht, T., Shen, D., Hundal, J., Fulton, R.S., Heath, S., Baty, J.D., Ding, L., Mardis, E.R., Westervelt, P., DiPersio, J.F., Walter, M.J., Graubert, T.A., Ley, T.J., Druley, T.E., Link, D.C., Wilson, R.K. The role of early TP53 mutations in the evolution of therapy-related AML. Nature, 2015 Feb 26;518(7540):552-5. PMID: 25487151

Alvarado, D. M., Yang, P., Druley, T. E., Lovett, M., Gurnett, C. A. (2014). Multiplexed direct genomic selection (MDiGS): a pooled BAC capture approach for highly accurate CNV and SNP/INDEL detection. Nucleic Acids Res, 42 (10), e82. PMCID: PMC4041413 PubMed: 24682816.

Valentine, M.C., Linabery, A.M., Chasnoff, S., Hughes, A.E., Mallaney, C., Sanchez, N., Giacalone, J., Heerema, N.A., Hilden, J.M., Spector, L.G., Ross, J.A.*, Druley, T.E.* (2014) Excess congenital non-synonymous variation in leukemia-associated genes in MLL- infant leukemia: a Children’s Oncology Group report. Leukemia. doi: 10.1038/leu.2013.367. PubMed: 24301523.

Ramos, E. I., Bien-Willner, G. A., Li, J., Hughes, A. E., Giacalone, J., Chasnoff, S., Kulkarni, S., Parmacek, M., Cole, F. S., Druley, T. E. (2013) Genetic variation in MKL2 and decreased downstream PCTAIRE1 expression in extreme, fatal primary human microcephaly. Clin Genet, doi: 10.1111/cge.12197. PubMed: 23692340.

Horani A*, Druley TE*, Zariwala MA, Levinson BT, VanArendonk LG, Thornton KC, Giacalone JC, Albee AJ, Wilson KS, Turner EH, Nickerson DA, Shendure J, Patel AC, Bayly PV, Leigh MW, Knowles MR, Brody SL, Dutcher SK, Ferkol TW. (2012) Whole exome capture and sequencing identifies HEATR2 mutation as a cause of primary ciliary dyskinesia. Am J Hum Genet. 2012 Oct 5;91(4):685-93. doi: 10.1016/j.ajhg.2012.08.022. PMCID: PMC3484505

Druley TE, Vallania FML, Varley KE, Knowles OL, Bonds JA, Doniger SW, Wegner DJ, Hamvas A, Cole FS, Fay JC and Mitra RD. (2009) Quantification of rare allelic variants from pooled genomic DNA. Nature Methods Apr; 6: 263-265. PMCID: PMC2776647

Druley TE, Hayashi R, Mansur DB, Zhang Q, Barnes Y, Trinkaus K, Witty S, Thomas T, Klein EE, DiPersio JF, Adkins D and Shenoy S. (2009) Early outcomes after allogeneic hematopoietic SCT in pediatric patients with hematologic malignancies following single fraction TBI. Bone Marrow Transplantation 43: 307-314. PMCID: PMC2792985

Last Updated: 8/24/2016 11:33:46 AM

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