Research

The Upadhyai lab focuses on the following major research areas:

I. Understanding primary cilia biogenesis, function and signaling based regulation in skeletal development, differentiation and homeostasis

The primary cilium is an immotile sensory organelle that receives and transduces diverse extracellular cues, such as mechanical signals and developmental morphogens. It is fundamental for cell growth, proliferation, differentiation, patterning and postnatal homeostasis. Defective primary cilia biogenesis and function result in a group of rare genetic disorders termed as ciliopathies. Many ciliopathies include rare skeletal disorders underscoring the pivotal role played by primary cilia in bone and cartilage formation, repair and remodeling.

We are interested in:

dissecting on primary cilia based molecular mechanisms that modulate osteogenic and chondrogenic differentiation programs using in vitro approaches
understanding how defects in ciliary proteins result in skeletal disorders

II. Developing a functional understanding for a wide range of rare genetic disorders

We perform collaborative human genetics research to uncover the pathomechanisms underlying a broad group of rare genetic diseases, such as skeletal and neurodevelopmental disorders.

Projects are initiated by the clinical evaluation of patients by our collaborators at the Department of Medical Genetics, Kasturba Medical College, Manipal. Whole exome or genome sequencing is performed to identify potential genetic cause(s). Following this we perform specific functional analyses using mammalian cell culture and Drosophila melanogaster to interrogate the pathogenicity of the genetic variants. This often provides a preliminary understanding of the disease mechanism and guides further studies.

III. Utilizing human population genetics and ancestry information to understand human disease biology

The genetic contribution to human diseases ranging from monogenic (single gene) to complex multifactorial etiology, as well as other human traits example, behavior is increasingly appreciated. In collaboration with other human geneticists in India we use population genetics tools to facilitate our understanding of human disease biology and evolutionary processes in worldwide human populations.