Regulation of gene expression by KDM5 family proteins
What we do
The Secombe Lab is part of the Department of Genetics and the Department of Neuroscience at Albert Einstein College of Medicine. We are interested in understanding the function of the KDM5 family of transcriptional regulators. KDM5 proteins have a unique combination of chromatin modifying and recognition domains that regulate gene expression through distinct mechanisms. In addition, an ever-growing body of evidence links their dysregulation to human pathologies. Of the four human KDM5 paralogs (KDM5A-D), three are clinically significant. KDM5A or KDM5B are overexpressed in a large number of cancers, and loss of function mutations in KDM5A, KDM5B and KDM5C are found in patients with X-linked intellectual disability. We use Drosophila and human organoid models to understand KDM5 function.
We use Drosophila and human organoid models to understand how KDM5 family proteins function in vivo. Drosophila are an animal model with a single kdm5 gene and an excellent genetic toolkit available to dissect KDM5 function. Human cells encode either three (XX individuals) or four (XY individuals) KDM5 genes - KDM5A, KDM5B, KDM5C and KDM5D.
KDM5 function in neurons (Drosophila)
To understand the link between KDM5 and neuronal development, we use fly strains genetically lacking kdm5, or harboring alleles analogous to those found in individuals with intellectual disability.
KDM5 function during development
KDM5 is essential for viability in Drosophila. This project aims to understand the mechanisms and transcriptional programs regulated by KDM5 needed for development.
KDM5C function in human cerebral organoids
Genetic variants in the X-linked gene KDM5C are associated with intellectual disability. To understand the transcriptional and cellular consequences of loss of KDM5C in a human cell context, we use iPSCs to generate cerebral organoids.