Research

Our current research focuses on birth of the hair follicle niche, growth control and regeneration, and tissue regression and reorganization.

Dynamics Underlying Tissue Integrity [R01 DK087650]

We hypothesize that tissue integrity results from the integration of information that arises from the dynamic interactions between the different cell types and the matrices that bind these cells together. To test this hypothesis we will focus on the kidney glomerular filtration barrier. In this system we predict that continuous information flow between a three-node loop consisting of podocytes cells, glomerular basement membrane and endothelial cells results in integrating the three entities into a single cohesive functional structure: the filtration barrier. Such information is both chemical (secreted autocrine /paracrine factors and cell/cell and cell/matrix contacts) and physical (forces arising from cell/cell and cell/matrix contacts). The information from physical and chemical sources is seamlessly integrated by intracellular signaling networks in the podocytes and endothelial cells to evoke responses that dynamically sustain the three-node loop, resulting in tissue integrity and functionality. This is a multi-investigator grant involving investigators from Icahn School of Medicine, Columbia University and the University of Connecticut.

Mechanisms of Interactions Between Signaling Pathways [R01 GM54508]

This grant supports the research on the organization and topology of signaling networks and information flow within the cell. Key discoveries from these studies have included the identification of pathway gating by the cAMP pathways, computational modeling of signaling networks to identify emergent properties and understanding the molecular mechanisms underlying the flexible design of positive feedback loops in biological systems.

Structure and Function of Signal Transducing Components [R01 DK038761]

The major goals of this project are to study the molecular interactions for signal transfer from G protein subunits to effectors. We are especially interested in understanding how high specificity is achieved in low to moderate affinity interactions during signal transfer through G alpha o subunits.

Modeling Cell Regulatory Networks [R01 GM072853]

This is a research project focused on systems biology at the cellular level. The overall goal of this project is to develop detailed spatial models of cell signaling networks to understand the origins and dynamics of microdomains of signaling components.