The goal of our laboratory is to understand the molecular basis of genetic and epigenetic abnormalities in different cancer types, and use that knowledge to improve personalized cancer diagnostics. Analyzing genomic amplifications and deletions from nearly three thousand cancer samples, we have recently reported that data on spatial proximity of regions replicating at the same time can be used to predict the mutational landscapes of cancer genomes (De & Michor. Nature Biotech. 2011). We also found that abnormal hypomethylation near G4s-rich regions is a common signature for many SCNA breakpoint hotspots. We propose a mechanistic hypothesis that abnormal hypomethylation in genomic regions enriched for G4s acts as a mutagenic factor driving tissue-specific mutational landscapes in cancer (De & Michor. Nature Struct Mol Biol. 2011).
We are applying a variety of genomics, bioinformatics and biostatistical approaches, and working in close collaboration with bench scientists, clinicians and biostatisticians to address scientific questions in related areas.
2012 NCI Physical Sciences Oncology Center (PSOC) Young Investigator Award. Grant co-PI.
2011 NCI PSOC Young Investigator Award. Grant PI (2011-2012).
2008 Junior Research Fellowship, King's College, Cambridge (2008-2012).
2000 Qualified to appear in Indian National Physics Olympiad (INPhO’2000).
2000 Qualified to appear in Indian National Chemistry Olympiad (INChO’2000).
1998 National Talent Search (NTS) Scholarship.
29: Pedersen BS, De S. (2013) Loss of heterozygosity preferentially occurs in early replicating regions in cancer genomes. Nucleic Acids Research (in press)
28: Pedersen BS, Konstantinopoulos PA, Spillman MA, De S. (2013) Copy neutral loss of heterozygosity is more frequent in older ovarian cancer patients. Genes, Chromosomes and Cancer. (in press). PMID: 23716468.
27: De S, Ward RM. (2013) Revisiting mutagenesis in the age of high-throughput sequencing. Chapter 13.Stress-Induced Mutagenesis. 284-90. Ed. David Mittelman. Springer Publishing Company.
26: De S, Shaknovich R, Riester M, Elemento O, Geng H, Kormaksson M et al. (2013) Aberration in DNA methylation in B-cell lymphomas has a complex origin and increases with disease severity. PLoS Genetics9(1):e1003137. PMID: 23326238.
25: Liu L, De S, Michor F. (2013) DNA replication timing and higher-order nuclear organization determine single-nucleotide substitution patterns in cancer genomes. Nature Communications 4:1502. PMID: 23422670.
24: Levy ED, De S, Teichmann SA. (2012) Cellular crowding imposes global constraints on the chemistry and evolution of proteomes. Proc Natl Acad Sci U S A. 109(50):20461-6. PMID: 23184996
23: Martins F, De S, Almendoro V, Gonen M et al. (2012) Evolutionary Pathways in BRCA1-Associated breast tumors. Cancer Discovery. 2(6):503-11. PMID: 22628410
22: Podlaha O, Riester M, De S, Michor F. (2012) Evolution of the cancer genome. Trends Genet. 27(6):217-23. PMID: 21496937.
21: De S, Michor F. (2012) Analyzing the association of SCNA boundaries with replication timing. Nature Biotechnology. 30(11):1045-6.
20: Antolin MF, Jenkins KP, Bergstrom CT, Crespi BJ, De S, Hancock A et al. (2012) Evolution and medicine in undergraduate education: a prescription for all biology students. Evolution. 66(6):1991-2006. PMID: 22671563
19: De S, Michor F. (2011) DNA secondary structures and epigenetic determinants of cancer genome evolution.Nature Structural and Molecular Biology.18(8):950-5. PMID: 21725294.
18: Shaknovich R, Cerchietti L, Tsikitas L, Kormaksson M, De S, Figueroa ME et al. (2011) DNA methyltransferase 1 and DNA methylation patterning contribute to germinal center B-cell differentiation. Blood. 118(13):3559-69. PMID: 21828137.
17: De S, Michor F. (2011) DNA replication timing and long-range DNA interactions predict mutational landscapes of cancer genomes. Nature Biotechnology. 29(12):1103-8. PMID: 22101487.
16: De S. (2011) Somatic mosaicism in healthy human tissues. Trends Genet.27(6):217-23. PMID: 21496937.
15: De S, Babu MM. (2010) A time-invariant principle of genome evolution. Proc Natl Acad Sci U S A. 107(29):13004-9. PMID: 20615949.
14: De S, Babu MM. (2010) Genomic neighbourhood and the regulation of gene expression. Curr Opin Cell Biol. 22(3) :326-33. PMID: 20493676.
13: Weber K, De S, Kozarewa I, Turner D, Babu MM, de Bono M. (2010) Genetic changes associated with laboratory domestication of the nematode. PLoS One. 5(11):e13922. PMID: 21085631.
12: Lister A, Charoensawan V, De S, James K, Janga SC, Huppert J. (2009) Interfacing systems biology and synthetic biology. Genome Biol. 10(6):309. PMID: 19591648
11: De S, Teichmann SA, Babu MM. (2009) The impact of genomic neighborhood on the evolution of human and chimpanzee transcriptome. Genome Res. 19(5):785-94. PMID: 19233772.
10: De S. (2009) The effect of a dynamic nuclear environment on gene expression. Nature. 460(7251):15. PMID: 19571840.
9: Watkins NA, Gusnanto A, de Bono B, De S, Miranda-Saavedra D et al. (2009) A HaemAtlas: characterizing gene expression in differentiated human blood cells. Blood. 113(19):e1-9. PMID: 19228925.
8: De S, Lopez-Bigas N, Teichmann SA. (2008) Patterns of evolutionary constraints on genes in humans. BMC Evol Biol. 2008 PMID: 18840274.
7: Miranda-Saavedra D, De S, Trotter MW, Teichmann SA, Göttgens B. (2009) BloodExpress: a database of gene expression in mouse haematopoiesis. Nucleic Acids Res. 37(Database issue):D873-9. PMID: 18987008
6: Loos RJ et al. (2008) Common variants near MC4R are associated with fat mass, weight and risk of obesity.Nat Genet. 40(6):768-75. PMID: 18454148. (more than 30 authors)
5: Lopez-Bigas N, De S, Teichmann SA. (2008) Functional protein divergence in the evolution of Homo sapiens.Genome Biol. 9(2):R33. PMID: 18279504.
4: Kindt KS, Quast KB, Giles AC, De S, Hendrey D, Nicastro I, Rankin CH, Schafer WR. (2007) Dopamine mediates context-dependent modulation of sensory plasticity in C. elegans. Neuron. 55(4):662-76. PMID: 17698017
3: De S, Pal D, Ghosh SK. (2006) Entamoeba histolytica: computational identification of putative microRNA candidates. Exp Parasitol. 113(4):239-43. PMID: 16515787.
2: De S, Krishnadev O, Srinivasan N, Rekha N. (2005) Interaction preferences across protein-protein interfaces of obligatory and non-obligatory components are different. BMC Struct Biol. 5:15. PMID: 16105176.
1: De S, Sur K, Dasgupta S. (2005) Characterization of the nonregular regions of proteins by a contortion index.Biopolymers. 79(2):63-73. PMID: 15962279