Research & Projects

Research in the Ahituv Lab focuses on understanding the role of regulatory sequences in biology and disease. Through a combination of comparative genomic strategies, genomic technologies (ChIP-seq, RNA-seq, ChIA-PET), human patient samples, mouse and fish genetic engineering technologies, and massively parallel reporter assays (MPRA), we are working to elucidate mechanisms whereby genetic variation within these sequences leads to changes in phenotypes. We are focusing on the following phenotypes:

Limb malformations

Limb malformations are the second most common form of human congenital abnormalities (prevalence of 1 in every 500 births), and very few gene mutations leading to non-syndromic/isolated limb malformations have been found. To this end, we are characterizing numerous novel limb enhancers in the human genome and collecting DNA from individuals with various limb malformations to screen them for mutations in these enhancers. More info: Limb Study.

Zebrafish with glowing fins

Zebrafish with glowing fins


A baby’s hand with an extra finger, an example of polydactyly

Bat wing development

The bat wing is one of the most striking examples of morphological variation in vertebrates, characterized by dramatically elongated fingers and retained interdigital webbing, enabling these mammals to fly. In collaboration with Dr. Nicola Illing (University of Cape Town), we are taking advantage of or unique ability to collect staged embryos from the Natal long-fingered bat, Miniopterus natalensis, along with our existing annotated genome for this species and RNA-seq and ChIP-seq datasets for developing forelimb and hindlimb autopods, to decipher the genetic changes that led to the evolution of the bat wing 55 million years ago.

blue-stained bat embryo

Miniopterus natalensis alizarin red/alcian blue stain bat embryo


Bat Accelerated Region

Image credit: bat embryo: Mandy K. Mason, University of Cape Town


By using comparative genomics, ChIP-seq, and zebrafish and mouse enhancer assays, we are analyzing how nucleotide changes in regulatory sequences can contribute to obesity.


SIM1 Candidate Enhancer 2 (SCE2)


Epilepsy is a complex and heterogeneous disease, which makes it difficult to precisely diagnose and provide an effective treatment. Mutations in gene regulatory elements could be a major cause of complex diseases such as epilepsy. In collaboration with the Birnbaum Lab, we are working to identify and characterize gene regulatory elements that could be associated with epilepsy and to screen epilepsy patients for mutations in these elements, thus improving the genetic diagnosis of epilepsy.

forebrain enhancer

A forebrain enhancer near FOXG1


Disruption of the AUTS2 gene and its regulatory elements has been found to be associated with autism, but the function and regulation of this gene is not well known. Using comparative genomics, ChIP-seq, zebrafish morpholinos, and zebrafish and mouse enhancer assays, we are characterizing the function and regulation of this gene.

Zebrafish embryos with GFP expression


We are characterizing how genetic differences in regulatory sequences, with a focus on regions surrounding membrane transport proteins, lead to clinical variation in response to drugs.

graph of rifampin-induced changes

Massively parallel reporter assays

In collaboration with the Shendure Lab we are developing technologies that can test thousands of sequences in parallel for their regulatory activity.

tail vein schematic
Smith RP et al., see below

Gene regulatory code

Using a combination of computational and functional studies, we are increasing our understanding of the gene regulatory code.

relationship diagram
Smith RP et al., see below

Image: Adapted from Smith RP et al., Nature Genetics 2013 45:1021-8