Imperial College London

ProfessorBorisLenhard

Faculty of MedicineInstitute of Clinical Sciences

Professor of Computational Biology
 
 
 
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Contact

 

+44 (0)20 3313 8353b.lenhard Website

 
 
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Assistant

 

Mr Alastair Douglas Ivor Williams +44 (0)20 3313 4318

 
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Location

 

230ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

140 results found

Danks GB, Navratilova P, Lenhard B, Thompson EMet al., 2018, Distinct core promoter codes drive transcription initiation at key developmental transitions in a marine chordate, BMC GENOMICS, Vol: 19, ISSN: 1471-2164

JOURNAL ARTICLE

Hill PWS, Leitch HG, Requena CE, Sun Z, Amouroux R, Roman-Trufero M, Borkowska M, Terragni J, Vaisvila R, Linnett S, Bagci H, Dharmalingham G, Haberle V, Lenhard B, Zheng Y, Pradhan S, Hajkova Pet al., 2018, Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte, NATURE, Vol: 555, Pages: 392-+, ISSN: 0028-0836

JOURNAL ARTICLE

Khan A, Fornes O, Stigliani A, Gheorghe M, Castro-Mondragon JA, van der Lee R, Bessy A, Cheneby J, Kulkarni SR, Tan G, Baranasic D, Arenillas DJ, Sandelin A, Vandepoele K, Lenhard B, Ballester B, Wasserman WW, Parcy F, Mathelier Aet al., 2018, JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework, NUCLEIC ACIDS RESEARCH, Vol: 46, Pages: D260-D266, ISSN: 0305-1048

JOURNAL ARTICLE

Khan A, Fornes O, Stigliani A, Gheorghe M, Castro-Mondragon JA, van der Lee R, Bessy A, Cheneby J, Kulkarni SR, Tan G, Baranasic D, Arenillas DJ, Sandelin A, Vandepoele K, Lenhard B, Ballester B, Wasserman WW, Parcy F, Mathelier Aet al., 2018, JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework (vol 46, pg 260, 2017), Publisher: OXFORD UNIV PRESS

OTHER

Lessel D, Gehbauer C, Bramswig NC, Schluth-Bolard C, Venkataramanappa S, van Gassen KLI, Hempel M, Haack TB, Baresic A, Genetti CA, Funari MFA, Lessel I, Kuhlmann L, Simon R, Liu P, Denecke J, Kuechler A, de Kruijff I, Shoukier M, Lek M, Mullen T, L├╝decke H-J, Lerario AM, Kobbe R, Krieger T, Demeer B, Lebrun M, Keren B, Nava C, Buratti J, Afenjar A, Shinawi M, Guillen Sacoto MJ, Gauthier J, Hamdan FF, Laberge A-M, Campeau PM, Louie RJ, Cathey SS, Prinz I, Jorge AAL, Terhal PA, Lenhard B, Wieczorek D, Strom TM, Agrawal PB, Britsch S, Tolosa E, Kubisch Cet al., 2018, BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells., Brain

The transcription factor BCL11B is essential for development of the nervous and the immune system, and Bcl11b deficiency results in structural brain defects, reduced learning capacity, and impaired immune cell development in mice. However, the precise role of BCL11B in humans is largely unexplored, except for a single patient with a BCL11B missense mutation, affected by multisystem anomalies and profound immune deficiency. Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B. Notably, all of them are affected by global developmental delay with speech impairment and intellectual disability; however, none displayed overt clinical signs of immune deficiency. Six frameshift mutations, two nonsense mutations, one missense mutation, and two chromosomal rearrangements resulting in diminished BCL11B expression, arose de novo. A further frameshift mutation was transmitted from a similarly affected mother. Interestingly, the most severely affected patient harbours a missense mutation within a zinc-finger domain of BCL11B, probably affecting the DNA-binding structural interface, similar to the recently published patient. Furthermore, the most C-terminally located premature termination codon mutation fails to rescue the progenitor cell proliferation defect in hippocampal slice cultures from Bcl11b-deficient mice. Concerning the role of BCL11B in the immune system, extensive immune phenotyping of our patients revealed alterations in the T cell compartment and lack of peripheral type 2 innate lymphoid cells (ILC2s), consistent with the findings described in Bcl11b-deficient mice. Unsupervised analysis of 102 T lymphocyte subpopulations showed that the patients clearly cluster apart from healthy children, further supporting the common aetiology of the disorder. Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodev

JOURNAL ARTICLE

Li C, Lenhard B, Luscombe NM, 2018, Integrated analysis sheds light on evolutionary trajectories of young transcription start sites in the human genome, GENOME RESEARCH, Vol: 28, Pages: 676-688, ISSN: 1088-9051

JOURNAL ARTICLE

Cantone I, Dharmalingam G, Chan Y-W, Kohler A-C, Lenhard B, Merkenschlager M, Fisher AGet al., 2017, Allele-specific analysis of cell fusion-mediated pluripotent reprograming reveals distinct and predictive susceptibilities of human X-linked genes to reactivation, GENOME BIOLOGY, Vol: 18, ISSN: 1474-760X

JOURNAL ARTICLE

Cvetesic N, Lenhard B, 2017, Core promoters across the genome, NATURE BIOTECHNOLOGY, Vol: 35, Pages: 123-124, ISSN: 1087-0156

JOURNAL ARTICLE

Harmston N, Ing-Simmons E, Tan G, Perry M, Merkenschlager M, Lenhard Bet al., 2017, Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723

JOURNAL ARTICLE

Polychronopoulos D, King JWD, Nash AJ, Tan G, Lenhard Bet al., 2017, Conserved non-coding elements: developmental gene regulation meets genome organization, NUCLEIC ACIDS RESEARCH, Vol: 45, ISSN: 0305-1048

JOURNAL ARTICLE

Siriboonpiputtana T, Zeisig BB, Zarowiecki M, Fung TK, Mallardo M, Tsai C-T, Lau PNL, Quoc CH, Veiga P, Barnes J, Lynn C, Wilson A, Lenhard B, So CWEet al., 2017, Transcriptional memory of cells of origin overrides beta-catenin requirement of MLL cancer stem cells, EMBO JOURNAL, Vol: 36, Pages: 3139-3155, ISSN: 0261-4189

JOURNAL ARTICLE

Adlakha A, Armstrong-James D, Lenhard B, 2016, Effect of calcineurin inhibition on phenotypic maturation of dendritic cells in an in-vitro model of invasive aspergillosis in lung transplant recipients, Spring Meeting on Clinician Scientists in Training, Publisher: ELSEVIER SCIENCE INC, Pages: 16-16, ISSN: 0140-6736

CONFERENCE PAPER

Adlakha A, Armstrong-James DAJ, Lenhard B, 2016, CALCINEURIN INHIBITION IMPAIRS THE DENDRITIC CELL TRANSCRIPTIONAL RESPONSE TO ASPERGILLUS FUMIGATUS INFECTION IN LUNG TRANSPLANT RECIPIENTS, THORAX, Vol: 71, Pages: A1-A1, ISSN: 0040-6376

JOURNAL ARTICLE

Cheung N, Fung TK, Zeisig BB, Holmes K, Rane JK, Mowen KA, Finn MG, Lenhard B, Chan LC, So CWEet al., 2016, Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia, CANCER CELL, Vol: 29, Pages: 32-48, ISSN: 1535-6108

JOURNAL ARTICLE

Cvetesic N, Dulic M, Bilus M, Sostaric N, Lenhard B, Gruic-Sovulj Iet al., 2016, Naturally Occurring Isoleucyl-tRNA Synthetase without tRNA-dependent Pre-transfer Editing, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 291, Pages: 8618-8631, ISSN: 0021-9258

JOURNAL ARTICLE

Haberle V, Lenhard B, 2016, Promoter architectures and developmental gene regulation, SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, Vol: 57, Pages: 11-23, ISSN: 1084-9521

JOURNAL ARTICLE

Kolder ICRM, van der Plas-Duivesteijn SJ, Tan G, Wiegertjes GF, Forlenza M, Guler AT, Travin DY, Nakao M, Moritomo T, Irnazarow I, den Dunnen JT, Anvar SY, Jansen HJ, Dirks RP, Palmblad M, Lenhard B, Henkel CV, Spaink HPet al., 2016, A full-body transcriptome and proteome resource for the European common carp, BMC GENOMICS, Vol: 17, ISSN: 1471-2164

JOURNAL ARTICLE

Mathelier A, Fornes O, Arenillas DJ, Chen C-Y, Denay G, Lee J, Shi W, Shyr C, Tan G, Worsley-Hunt R, Zhang AW, Parcy F, Lenhard B, Sandelin A, Wasserman WWet al., 2016, JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles, NUCLEIC ACIDS RESEARCH, Vol: 44, Pages: D110-D115, ISSN: 0305-1048

JOURNAL ARTICLE

Nepal C, Coolen M, Hadzhiev Y, Cussigh D, Mydel P, Steen VM, Carninci P, Andersen JB, Bally-Cuif L, Muller F, Lenhard Bet al., 2016, Transcriptional, post-transcriptional and chromatin-associated regulation of pri-miRNAs, pre-miRNAs and moRNAs, NUCLEIC ACIDS RESEARCH, Vol: 44, Pages: 3070-3081, ISSN: 0305-1048

JOURNAL ARTICLE

Tan G, Lenhard B, 2016, TFBSTools: an R/bioconductor package for transcription factor binding site analysis, BIOINFORMATICS, Vol: 32, Pages: 1555-1556, ISSN: 1367-4803

JOURNAL ARTICLE

Adlakha AG, Armstrong-James DPH, Lenhard B, 2015, CALCINEURIN INHIBITION IMPAIRS PHENOTYPIC MATURATION OF DENDRITIC CELLS IN A IN VITRO MODEL OF INVASIVE ASPERGILLOSIS IN LUNG TRANSPLANT RECIPIENTS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A48-A49, ISSN: 0040-6376

CONFERENCE PAPER

Danks GB, Raasholm M, Campsteijn C, Long AM, Manak JR, Lenhard B, Thompson EMet al., 2015, Trans-Splicing and Operons in Metazoans: Translational Control in Maternally Regulated Development and Recovery from Growth Arrest, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 32, Pages: 585-599, ISSN: 0737-4038

JOURNAL ARTICLE

Haberle V, Forrest ARR, Hayashizaki Y, Carninci P, Lenhard Bet al., 2015, CAGEr: precise TSS data retrieval and high-resolution promoterome mining for integrative analyses, NUCLEIC ACIDS RESEARCH, Vol: 43, ISSN: 0305-1048

JOURNAL ARTICLE

Harmston N, Baresic A, Lenhard B, 2015, The mystery of extreme non-coding conservation (vol 368, 20130021, 2013), Publisher: ROYAL SOC

OTHER

Harmston N, Ing-Simmons E, Perry M, Baresic A, Lenhard Bet al., 2015, GenomicInteractions: An R/Bioconductor package for manipulating and investigating chromatin interaction data, BMC GENOMICS, Vol: 16, ISSN: 1471-2164

JOURNAL ARTICLE

Hurst LD, Ghanbarian AT, Forrest ARR, FANTOM consortium, Huminiecki Let al., 2015, The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome., PLoS Biol, Vol: 13

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression

JOURNAL ARTICLE

Ing-Simmons E, Seitan VC, Faure AJ, Flicek P, Carroll T, Dekker J, Fisher AG, Lenhard B, Merkenschlager Met al., 2015, Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin, GENOME RESEARCH, Vol: 25, Pages: 504-513, ISSN: 1088-9051

JOURNAL ARTICLE

Ishibashi M, Manning E, Shoubridge C, Krecsmarik M, Hawkins TA, Giacomotto J, Zhao T, Mueller T, Bader PI, Cheung SW, Stankiewicz P, Bain NL, Hackett A, Reddy CCS, Mechaly AS, Peers B, Wilson SW, Lenhard B, Bally-Cuif L, Gecz J, Becker TS, Rinkwitz Set al., 2015, Copy number variants in patients with intellectual disability affect the regulation of ARX transcription factor gene, HUMAN GENETICS, Vol: 134, Pages: 1163-1182, ISSN: 0340-6717

JOURNAL ARTICLE

Naville M, Ishibashi M, Ferg M, Bengani H, Rinkwitz S, Krecsmarik M, Hawkins TA, Wilson SW, Manning E, Chilamakuri CSR, Wilson DI, Louis A, Raymond FL, Rastegar S, Straehle U, Lenhard B, Bally-Cuif L, van Heyningen V, FitzPatrick DR, Becker TS, Roest Crollius Het al., 2015, Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome, NATURE COMMUNICATIONS, Vol: 6, ISSN: 2041-1723

JOURNAL ARTICLE

Stadhouders R, Cico A, Stephen T, Thongjuea S, Kolovos P, Baymaz HI, Yu X, Demmers J, Bezstarosti K, Maas A, Barroca V, Kockx C, Ozgur Z, van Ijcken W, Arcangeli M-L, Andrieu-Soler C, Lenhard B, Grosveld F, Soler Eet al., 2015, Control of developmentally primed erythroid genes by combinatorial co-repressor actions, NATURE COMMUNICATIONS, Vol: 6, ISSN: 2041-1723

JOURNAL ARTICLE

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