Welcome to the Karpen Laboratory

Our studies are focused on understanding inheritance, chromatin structure, gene expression, and the organization of chromosomes in the nucleus. Most of our studies have focused on the fruit fly Drosophila melanogaster as a model for chromosome function in metazoans, which allows us to address mechanisms in animals by synergistically combining molecular, genetic, cell biological and biochemical approaches. Additionally, we have examined the relevance of our findings to human chromosomes, and have demonstrated surprising similarities between these evolutionarily-distant species.

Current lab projects

Centromere assembly

Centromeres mediate proper chromatid segregation during mitosis and meiosis. Interestingly, the sequence of these DNA-based elements is not conserved; rather their identity is passed on in an epigenetic manner via a histone H3 variant known as CENP-A in humans and CID in Drosophila. We study the process of loading this histone variant into chromatin and how CENP-A and its loading chaperone HJURP affect centromere function in normal and cancerous cells.

Heterochromatin

Nuclear architecture directly regulates nuclear functions. Generally, the nucleus is divided into two large compartments known as euchromatin, which contains most protein-coding genes, and heterochromatin, which mainly contains the 'junk' DNA like transposons and simple repeats. Proper targeting of sequences into each compartment is necessary for genome stability and gene regulation. We study regulation of structural heterochromatic proteins and their effect on nuclear, cellular and physiological phenotypes.

DNA damage repair

Our genomes are constantly under attack by environmental and endogenous factors that leave single and double-stranded DNA breaks all over our chromosomes. Luckily, our cells have many efficient ways of repairing this damage, including Homology Directed Repair, which fixes the DNA without any trace by copying a sister chromatid. This process becomes complicated, however, in highly repetitive heterochromatic sequences. We study the process of repair in context of different epigenetic environments, with the goal of learning how a cell decides which repair pathway to choose.