The principal research interests of the Nathans lab center on two areas: (1) the structure and function of the vertebrate visual system and (2) the origins of pattern formation in development. 
 
The Nathans laboratory is approaching questions related to the visual system by studying the retina.  The questions we are asking are: (1)  How are the patterns of cell identity in the retina determined at a molecular level?  (2)  How is the final performance of the system affected by individual molecules and molecular events?  (3)  How is the remarkable structure of photoreceptor cells generated?  (4)  What are the pathologic mechanisms responsible for blinding diseases and how can this knowledge be applied to therapeutic intervention? 
 
Research in the Nathans laboratory on pattern formation focuses on the mechanism of action and biological role of a large family of transmembrane receptors referred to as "Frizzled" proteins, a name that reflects the odd appearance of those Drosophila in which one of the Frizzled genes is mutated.  The Frizzled proteins act as receptors for a family of secreted signaling proteins referred to as Wnts, but at least one non-Wnt ligand activates one of the Frizzleds.  Using knock-out mice, we have shown that a remarkably diverse group of developmental processes relies on Frizzled action, including blood vessel development in the retina, development of the cerebellum, axonal growth and  path finding in the spinal cord and forebrain, and hair patterning on the body surface. We are currently investigating the mechanisms underlying Frizzled action in these various contexts, and searching for additional roles of Frizzled proteins.
 
In both areas of research, the Nathans laboratory uses genetically engineered mice, cell culture approaches, in vitro biochemical experiments with purified proteins, and the analysis of genes and proteins responsible for inherited human diseases.