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Harmen Bussemaker

Abstract

Harmen Bussemaker

Title:
Dissecting transcription factor networks using high-throughput sequencing and quantitative genetics

Abstract:
In this talk I will describe our recent efforts to elucidate the molecular interactions underlying the behavior of gene regulatory networks. I will first demonstrate how deep sequencing of interactions between DNaseI and naked DNA uncovers a strong dependence of cleavage rate on nucleotide sequence, which can be related to the width of the minor groove; an additional, equally striking dependence on CpG methylation status exists, allowing us to predict methylation status from in vivo DNaseI profiles. Next, I will show how SELEX-seq, a novel methodology for quantifying in vitro interactions between transcription factor complexes and DNA, allowed us to discover that heterodimerization with the cofactor Extradenticle gives rise to large differences in DNA binding specificity between Hox proteins that are absent when these proteins bind as monomers. Finally, I will demonstrate how linear modeling of genetic variation in mRNA expression levels combined with prior information about the DNA binding specificity of transcription factors can be used to map the loci ("aQTLs") whose allelic variation modulates their regulatory activity.

Professional carreer

Biography:
Harmen Bussemaker is a tenured Associate Professor in the Department of Biological Sciences at Columbia University, and a core faculty member of Columbia’s Center for Computational Biology and Bioinformatics (C2B2). His credentials include a Lenfest Distinguished Columbia Faculty Award and a John Simon Guggenheim Foundation Fellowship. Dr. Bussemaker is known for his pioneering work aimed at understanding gene regulatory networks based on the integration of genome sequence, transcription factor binding, and gene expression data. Ongoing research in the Bussemaker lab aims to quantify the DNA binding specificity of transcription factors at unprecedented resolution using high-throughput sequencing coupled with affinity-based selection; infer cell-state specific changes in the regulatory activity of transcription factors from genomewide mRNA expression levels using biophysical models; exploit natural genetic variation to dissect complex cis-regulatory logic; and understand how local chromatin context modulates the influence of transcription factor on its target genes.

Education:

  • 2010 - Summer Course on Yeast Genetics and Genomics, Cold Spring Harbor Laboratories
  • 1991-1995 - Ph.D. in Theoretical Physics, Utrecht University, The Netherlands
  • 1986-1991 - M.Sc. in Theoretical Physics, Utrecht University, The Netherlands
  • 1987-1989 - B.A. in Musicology, Utrecht University, The Netherlands

Employment:

  • 2007 - present Associate Professor (tenured), Department of Biological Sciences Columbia University, New York, NY, USA
  • 2010-2011  - Sabbatical Visitor, Lewis-Sigler Institute, Princeton University
  • 2009 - Visiting Professor, Netherlands Cancer Institute, Amsterdam
  • 2001 - Member, Center for Computational Biology and Bioinformatics Columbia University Medical Center, New York, NY, USA
  • 2001-2007 - Assistant Professor, Department of Biological Sciences Columbia University, New York, NY, USA
  • 1999-2001 - Lecturer (“Universitair Docent”), Swammerdam Institute for Life Sciences University of Amsterdam, The Netherlands
  • 1997-1999 - Postdoctoral Associate, Center for Studies in Physics and Biology
    The Rockefeller University, New York, NY, USA
  • 1995-1997 - Research Associate, Institute for Physical Science and Technology
    University of Maryland, College Park, MD, USA