Honoratus Van Bakel
- ASSISTANT PROFESSOR Genetics and Genomic Sciences
M.S., University of Utrecht
Ph.D., University of Utrecht
Bioinformatics and Molecular Biology
- Harm van Bakel's research is focused on understanding genome architecture, transcription regulation and coding- and non-coding RNA biology, with an emphasis on their relationship to disease. He uses a combination of Molecular Biology and Bioinformatics approaches to tackle these questions.
De novo reconstruction of transcriptomesWhole-genome transcriptome profiling has been widely used to assess the cellular state, but the need for reference genome and transcriptome sequences has restricted many of these analyses to well-studied model organisms. More recently, NGS technologies coupled with de novo assembly have made it possible to obtain transcriptome data for organisms that are not experimentally tractable, as well as from complex environments such as the microbial communities that inhabit our skin and gastrointestinal tract. We are using de novo assembly approaches to reconstruct the metabolic state of human microbial communities and how changes in this metabolism affect the host. In addition, we are reconstructing transcriptional regulatory networks in medicinal plants with the aim of increasing the production of medicinal compounds and enhancing their potential to treat disease.
Regulation of alternative splicingAlternative splicing (AS) is one of the mechanisms by which differentiated, non-dividing, cells can change their proteome composition. Over the past years, rapid developments in NGS have led to the identification of large numbers of AS events for protein coding transcripts in humans and other higher eukaryotes, however, comparatively little is known of how these events are regulated. Errors in RNA splicing, for example through mutations that alter existing splice sites or through the creation of cryptic sites, have been linked to a variety of human diseases. Our lab is developing novel sequencing approaches to identify the key RNA elements and sequence motifs involved in splicing and the regulation of alternative splicing. We also plan to evaluate the functional effects of mutations in these motifs and their implication for disease.
The role of long non-coding RNAs in gene regulatory networksThe RNA ecosystem has significantly expanded in recent years, with the identification of new transcript categories in humans and other eukaryotes that thus far remain largely uncharacterized. These include a class of large intergenic non-coding RNAs (lincRNAs) that can be differentiated from other non-coding RNAs based on their length (~1 kb on average), separation from protein-coding genes, and degree of conservation. Like mRNAs, lincRNAs can undergo splicing and are expressed in tissue-specific patterns. While the vast majority of lincRNAs remain poorly characterized, recent studies of individual cases have implicated them in a variety of cellular functions such as the regulation of chromatin state and gene expression, and highlighted their relevance for disease. Previously, we have identified hundreds of new lincRNA candidates that are transcribed in evolutionary conserved regions in the genome. Current research in the lab is focused on using next-generation sequencing (NGS) technologies such as RNA-Seq, ChIP-Seq and RIP-Seq to elucidate the role of these and other lincRNAs in epigenetic and gene regulatory networks. The results of this research will help guide development of new methodologies to rewire these networks for future therapeutic interventions.
van Bakel H, Tsui K, Gebbia M, Mnaimneh S, Hughes TR, Nislow C. A compendium of nucleosome and transcript profiles reveals determinants of chromatin architecture and transcription. PLoS Genetics 2013;: in press.
Drogat J, Migeot V, Mommaerts E, Mullier C, Dieu M, van Bakel H, Hermand D. Cdk11-CyclinL Controls the Assembly of the RNA Polymerase II Mediator Complex. Cell reports 2012 Oct;.
van Bakel H, Stout JM, Cote AG, Tallon CM, Sharpe AG, Hughes TR, Page JE. The draft genome and transcriptome of Cannabis sativa. Genome biology 2011; 12(10).
van Bakel H. Interactions of transcription factors with chromatin. Sub-cellular biochemistry 2011; 52.
Lam KN, van Bakel H, Cote AG, van der Ven A, Hughes TR. Sequence specificity is obtained from the majority of modular C2H2 zinc-finger arrays. Nucleic acids research 2011 Jun; 39(11).
Coudreuse D, van Bakel H, Dewez M, Soutourina J, Parnell T, Vandenhaute J, Cairns B, Werner M, Hermand D. A gene-specific requirement of RNA polymerase II CTD phosphorylation for sexual differentiation in S. pombe. Current biology : CB 2010 Jun; 20(12).
van Bakel H, Nislow C, Blencowe BJ, Hughes TR. Most dark matter transcripts are associated with known genes.. PLoS biology 2010 May; 8(5).
van Bakel H, Hughes TR. Establishing legitimacy and function in the new transcriptome. Briefings in functional genomics & proteomics 2009 Nov; 8(6).
Khanna M, Van Bakel H, Tang X, Calarco JA, Babak T, Guo G, Emili A, Greenblatt JF, Hughes TR, Krogan NJ, Blencowe BJ. A systematic characterization of Cwc21, the yeast ortholog of the human spliceosomal protein SRm300. RNA (New York, N.Y.) 2009 Dec; 15(12).
Badis G, Chan ET, van Bakel H, Pena-Castillo L, Tillo D, Tsui K, Carlson CD, Gossett AJ, Hasinoff MJ, Warren CL, Gebbia M, Talukder S, Yang A, Mnaimneh S, Terterov D, Coburn D, Li Yeo A, Yeo ZX, Clarke ND, Lieb JD, Ansari AZ, Nislow C, Hughes TR. A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Molecular cell 2008 Dec; 32(6).
van Werven FJ, van Bakel H, van Teeffelen HA, Altelaar AF, Koerkamp MG, Heck AJ, Holstege FC, Timmers HT. Cooperative action of NC2 and Mot1p to regulate TATA-binding protein function across the genome. Genes & development 2008 Sep; 22(17).
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Van Bakel did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
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