Imperial College London

DrSantoshAtanur

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Genome Data Scientist
 
 
 
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Contact

 

+44 (0)20 7594 2739santosh.atanur

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

20 results found

Watson S, Duff J, Bardi I, Zabielska M, Atanur S, Jabbour R, Simon A, Tomas A, Smolenski R, Harding S, Terracciano Cet al., 2019, Biomimetic electromechanical stimulation to maintain adult myocardial slices in vitro, Nature Communications, Vol: 10, ISSN: 2041-1723

Adult cardiac tissue undergoes a rapid process of dedifferentiation when cultured outside the body. The in vivo environment, particularly constant electromechanical stimulation, is fundamental to the regulation of cardiac structure and function. We investigated the role of electromechanical stimulation in preventing culture-induced dedifferentiation of adult cardiac tissue using rat, rabbit and human heart failure myocardial slices. Here we report that the application of a preload equivalent to sarcomere length (SL) = 2.2 μm is optimal for the maintenance of rat myocardial slice structural, functional and transcriptional properties at 24 h. Gene sets associated with the preservation of structure and function are activated, while gene sets involved in dedifferentiation are suppressed. The maximum contractility of human heart failure myocardial slices at 24 h is also optimally maintained at SL = 2.2 μm. Rabbit myocardial slices cultured at SL = 2.2 μm remain stable for 5 days. This approach substantially prolongs the culture of adult cardiac tissue in vitro.

Journal article

Rajani RM, Quick S, Ruigrok SR, Graham D, Harris SE, Verhaaren BFJ, Fornage M, Seshadri S, Atanur SS, Dominiczak AF, Smith C, Wardlaw JM, Williams Aet al., 2018, Reversal of endothelial dysfunction reduces white matter vulnerability in cerebral small vessel disease in rats, Science Translational Medicine, Vol: 10, Pages: eaam9507-eaam9507, ISSN: 1946-6234

Journal article

Black HA, Parry D, Atanur SS, Ross D, Rose E, Russell H, Stock S, Warner J, Porteous M, Aitman TJ, Evans MJet al., 2016, De novo mutations in autosomal recessive congenital malformations, GENETICS IN MEDICINE, Vol: 18, Pages: 1325-1326, ISSN: 1098-3600

Journal article

Abdelmagid N, Bereczky-Veress B, Atanur S, Musilova A, Zidek V, Saba L, Warnecke A, Khademi M, Studahl M, Aurelius E, Hjalmarsson A, Garcia-Diaz A, Denis CV, Bergstrom T, Skoldenberg B, Kockum I, Aitman T, Huebner N, Olsson T, Pravenec M, Diez Met al., 2016, Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis, PLOS One, Vol: 11, ISSN: 1932-6203

Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines—generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89–174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11–2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

Journal article

Zhao L, Oliver E, Maratou K, Atanur SS, Dubois OD, Cotroneo E, Chen CN, Wang L, Arce C, Chabosseau PL, Ponsa-Cobas J, Frid MG, Moyon B, Webster Z, Aldashev A, Ferrer J, Rutter GA, Stenmark KR, Aitman TJ, Wilkins MRet al., 2015, The zinc transporter, ZIP12, regulates the pulmonary vascular response to chronic hypoxia, Nature, Vol: 524, Pages: 356-360, ISSN: 0028-0836

The typical response of the adult mammalian pulmonary circulation to a low oxygen environment is vasoconstriction and structural remodelling of pulmonary arterioles, leading to chronic elevation of pulmonary artery pressure (pulmonary hypertension) and right ventricular hypertrophy. Some mammals, however, exhibit genetic resistance to hypoxia-induced pulmonary hypertension1, 2, 3. We used a congenic breeding program and comparative genomics to exploit this variation in the rat and identified the gene Slc39a12 as a major regulator of hypoxia-induced pulmonary vascular remodelling. Slc39a12 encodes the zinc transporter ZIP12. Here we report that ZIP12 expression is increased in many cell types, including endothelial, smooth muscle and interstitial cells, in the remodelled pulmonary arterioles of rats, cows and humans susceptible to hypoxia-induced pulmonary hypertension. We show that ZIP12 expression in pulmonary vascular smooth muscle cells is hypoxia dependent and that targeted inhibition of ZIP12 inhibits the rise in intracellular labile zinc in hypoxia-exposed pulmonary vascular smooth muscle cells and their proliferation in culture. We demonstrate that genetic disruption of ZIP12 expression attenuates the development of pulmonary hypertension in rats housed in a hypoxic atmosphere. This new and unexpected insight into the fundamental role of a zinc transporter in mammalian pulmonary vascular homeostasis suggests a new drug target for the pharmacological management of pulmonary hypertension.

Journal article

Wang J, Ma MCJ, Mennie AK, Pettus JM, Xu Y, Lin L, Traxler MG, Jakoubek J, Atanur SS, Aitman TJ, Xing Y, Kwitek AEet al., 2015, Systems Biology With High-Throughput Sequencing Reveals Genetic Mechanisms Underlying the Metabolic Syndrome in the Lyon Hypertensive Rat, CIRCULATION-CARDIOVASCULAR GENETICS, Vol: 8, Pages: 316-326, ISSN: 1942-325X

Journal article

Johnson MD, Mueller M, Adamowicz-Brice M, Collins MJ, Gellert P, Maratou K, Srivastava PK, Rotival M, Butt S, Game L, Atanur SS, Silver N, Norsworthy PJ, Langley SR, Petretto E, Pravenec M, Aitman TJet al., 2014, Genetic Analysis of the Cardiac Methylome at Single Nucleotide Resolution in a Model of Human Cardiovascular Disease, PLOS GENETICS, Vol: 10, ISSN: 1553-7404

Journal article

Baud A, Guryev V, Hummel O, Johannesson M, Flint J, Hermsen R, Stridh P, Graham D, McBride MW, Foroud T, Calderari S, Diez M, Ockinger J, Beyeen AD, Gillett A, Abdelmagid N, Guerreiro-Cacais AO, Jagodic M, Tuncel J, Norin U, Beattie E, Huynh N, Miller WH, Koller DL, Alam I, Falak S, Osborne-Pellegrin M, Martinez-Membrives E, Canete T, Blazquez G, Vicens-Costa E, Mont-Cardona C, Diaz-Moran S, Tobena A, Zelenika D, Saar K, Patone G, Bauerfeind A, Bihoreau MT, Heinig M, Lee YA, Rintisch C, Schulz H, Wheeler DA, Worley KC, Muzny DM, Gibbs RA, Lathrop M, Lansu N, Toonen P, Ruzius FP, De Bruijn E, Hauser H, Adams DJ, Keane T, Atanur SS, Aitman TJ, Flicek P, Malinauskas T, Jones EY, Ekman D, Lopez-Aumatell R, Dominiczak AF, Holmdahl R, Olsson T, Gauguier D, Hubner N, Fernandez-Teruel A, Cuppen E, Mott Ret al., 2014, Genomes and phenomes of a population of outbred rats and its progenitors, Scientific Data, Vol: 1

Finding genetic variants that contribute to phenotypic variation is one of the main challenges of modern genetics. We used an outbred population of rats (Heterogeneous Stock, HS) in a combined sequence-based and genetic mapping analysis to identify sequence variants and genes contributing to complex traits of biomedical relevance. Here we describe the sequences of the eight inbred progenitors of the HS and the variants that segregate between them. We report the genotyping of 1,407 HS rats, and the collection from 2,006 rats of 195 phenotypic measures that are relevant to models of anxiety, type 2 diabetes, hypertension and osteoporosis. We make available haplotype dosages for the 1,407 genotyped rats, since genetic mapping in the HS is best carried out by reconstructing each HS chromosome as a mosaic of the progenitor genomes. Finally, we have deposited an R object that makes it easy to incorporate our sequence data into any genetic study of HS rats. Our genetic data are available for both Rnor3.4 and Rnor5.0 rat assemblies.

Journal article

Ma MCJ, Atanur SS, Aitman TJ, Kwitek AEet al., 2014, Genomic structure of nucleotide diversity among Lyon rat models of metabolic syndrome, BMC GENOMICS, Vol: 15, ISSN: 1471-2164

Journal article

Vandrovcova J, Thomas ERA, Atanur SS, Norsworthy PJ, Neuwirth C, Tan Y, Kasperaviciute D, Biggs J, Game L, Mueller M, Soutar AK, Aitman TJet al., 2013, The use of next-generation sequencing in clinical diagnosis of familial hypercholesterolemia, GENETICS IN MEDICINE, Vol: 15, Pages: 948-957, ISSN: 1098-3600

Journal article

Thomas ERA, Atanur SS, Norsworthy PJ, Encheva V, Snijders AP, Game L, Vandrovcova J, Siddiq A, Seed M, Soutar AK, Aitman TJet al., 2013, Identification and biochemical analysis of a novel APOB mutation that causes autosomal dominant hypercholesterolemia., Mol Genet Genomic Med, Vol: 1, Pages: 155-161, ISSN: 2324-9269

Patients with autosomal dominant hypercholesterolemia (ADH) have a high risk of developing cardiovascular disease that can be effectively treated using statin drugs. Molecular diagnosis and family cascade screening is recommended for early identification of individuals at risk, but up to 40% of families have no mutation detected in known genes. This study combined linkage analysis and exome sequencing to identify a novel variant in exon 3 of APOB (Arg50Trp). Mass spectrometry established that low-density lipoprotein (LDL) containing Arg50Trp APOB accumulates in the circulation of affected individuals, suggesting defective hepatic uptake. Previously reported mutations in APOB causing ADH have been located in exon 26. This is the first report of a mutation outside this region causing this phenotype, therefore, more extensive screening of this large and highly polymorphic gene may be necessary in ADH families. This is now feasible due to the high capacity of recently available sequencing platforms.

Journal article

Atanur SS, Garcia-Diaz A, Maratou K, Sarkis A, Rotival M, Game L, Tschannen MR, Kaisaki PJ, Otto GW, Ma MCJ, Keane TM, Hummel O, Saar K, Chen W, Guryev V, Gopalakrishnan K, Garrett MR, Joe B, Citterio L, Bianchi G, McBride M, Dominiczak A, Adams DJ, Serikawa T, Flicek P, Cuppen E, Hubner N, Petretto E, Gaugier D, Kwitek A, Jacob H, Aitman TJet al., 2013, Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat., Cell

Journal article

Pillai R, Waghulde H, Nie Y, Gopalakrishnan K, Kumarasamy S, Farms P, Garrett MR, Atanur SS, Maratou K, Aitman TJ, Joe Bet al., 2013, Isolation and high-throughput sequencing of two closely linked epistatic hypertension susceptibility loci with a panel of bicongenic strains, PHYSIOLOGICAL GENOMICS, Vol: 45, Pages: 729-736, ISSN: 1094-8341

Journal article

Baud A, Hermsen R, Guryev V, Stridh P, Graham D, McBride MW, Foroud T, Calderari S, Diez M, Ockinger J, Beyeen AD, Gillett A, Abdelmagid N, Guerreiro-Cacais AO, Jagodic M, Tuncel J, Norin U, Beattie E, Ngan H, Miller WH, Koller DL, Alam I, Falak S, Osborne-Pellegrin M, Martinez-Membrives E, Canete T, Blazquez G, Vicens-Costa E, Mont-Cardona C, Diaz-Moran S, Tobena A, Hummel O, Zelenika D, Saar K, Patone G, Bauerfeind A, Bihoreau M-T, Heinig M, Lee Y-A, Rintisch C, Schulz H, Wheeler DA, Worley KC, Muzny DM, Gibbs RA, Lathrop M, Lansu N, Toonen P, Ruzius FP, de Bruijn E, Hauser H, Adams DJ, Keane T, Atanur SS, Aitman TJ, Flicek P, Malinauskas T, Jones EY, Ekman D, Lopez-Aumatell R, Dominiczak AF, Johannesson M, Holmdahl R, Olsson T, Gauguier D, Hubner N, Fernandez-Teruel A, Cuppen E, Mott R, Flint Jet al., 2013, Combined sequence-based and genetic mapping analysis of complex traits in outbred rats, NATURE GENETICS, Vol: 45, Pages: 767-+, ISSN: 1061-4036

Journal article

Hull RP, Srivastava PK, D'Souza Z, Atanur SS, Mechta-Grigoriou F, Game L, Petretto E, Cook HT, Aitman TJ, Behmoaras Jet al., 2013, Combined ChIP-Seq and transcriptome analysis identifies AP-1/JunD as a primary regulator of oxidative stress and IL-1 beta synthesis in macrophages, BMC GENOMICS, Vol: 14, ISSN: 1471-2164

Journal article

Johnson MD, Mueller M, Game L, Aitman TJet al., 2012, Single Nucleotide Analysis of Cytosine Methylation by Whole-Genome Shotgun Bisulfite Sequencing

Unlike other methods to assess methylation, whole-genome shotgun bisulfite sequencing is used to generate quantitative genome-wide methylation profiles at single-nucleotide resolution. As described in this unit, this method allows for the quantitative measurement of methylation at each cytosine base by treatment of genomic DNA with sodium bisulfite followed by sequencing and alignment of the reads to a reference genome. Curr. Protoc. Mol. Biol. 99:21.23.1-21.23.28. © 2012 by John Wiley & Sons, Inc.

Journal article

Morrissey C, Grieve IC, Heinig M, Atanur S, Petretto E, Pravenec M, Hubner N, Aitman TJet al., 2011, Integrated genomic approaches to identification of candidate genes underlying metabolic and cardiovascular phenotypes in the spontaneously hypertensive rat, PHYSIOLOGICAL GENOMICS, Vol: 43, Pages: 1207-1218, ISSN: 1094-8341

Journal article

Atanur SS, Birol I, Guryev V, Hirst M, Hummel O, Morrissey C, Behmoaras J, Fernandez-Suarez XM, Johnson MD, McLaren WM, Patone G, Petretto E, Plessy C, Rockland KS, Rockland C, Saar K, Zhao Y, Carninci P, Flicek P, Kurtz T, Cuppen E, Pravenec M, Hubner N, Jones SJM, Birney E, Aitman TJet al., 2010, The genome sequence of the spontaneously hypertensive rat: Analysis and functional significance, GENOME RESEARCH, Vol: 20, Pages: 791-803, ISSN: 1088-9051

Journal article

Patil DP, Atanur S, Dhotre DP, Anantharam D, Mahajan VS, Walujkar SA, Chandode RK, Kulkarni GJ, Ghate PS, Srivastav A, Dayananda KM, Gupta N, Bhagwat B, Joshi RR, Mourya DT, Patole MS, Shouche YSet al., 2009, Generation, annotation, and analysis of ESTs from midgut tissue of adult female Anopheles stephensi mosquitoes, BMC Genomics, Vol: 10, Pages: 386-386, ISSN: 1471-2164

Journal article

Rangrez AY, Dayananda KM, Atanur S, Joshi R, Patole MS, Shouche YSet al., 2006, Detection of Conjugation Related Type Four Secretion Machinery in Aeromonas culicicola, PLoS ONE, Vol: 1, Pages: e115-e115

Journal article

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