Scientific image of MCWH

A hallmark of many diseases and cancers is a dysfunctional cytoskeleton. A properly functioning cytoskeleton is needed for a wide variety of cellular events ranging from cell shape to cell signaling and migration/metastasis. We use multidisciplinary approaches to study these dynamic structural elements in various processes including wound repair and nuclear architecture/organization. Our goal is to understand the role of these elements in regulating normal developmental events and how this regulation goes awry in diseases/cancers, thereby providing new avenues for possible therapeutic targets or to enhance the effectiveness of existing treatment modalities.

Current research efforts

Wound Healing

We are investigating the cellular and molecular mechanisms of single cell and multicellular (tissue) wound repair and their ensuing biological manifestations, in the embryo. We are particularly interested in the regulation of the actin cytoskeleton and in the role of the Rho family of small GTPases in these processes.

Nuclear Architecture/Organization

We recently identified Wash, a new subfamily of WAS proteins, that functions downstream of the Rho1 GTPase, exhibits Arp2/3 dependent branched actin nucleation activity, exhibits actin and microtubule bundling and crosslinking activities, and interacts with the actin nucleation factors Capu (formin) and Spire. In addition to its cytoplasmic localization and roles, we find that Wash is expressed in the nucleus.

Rho GTPases

We are currently investigating the molecular mechanisms associated with Rho1 and three of its downstream effectors: the de novo linear actin nucleation factors Capu (a formin-homology protein) and Spire (a WH2 domain protein), which act downstream of Rho1 to regulate the onset of ooplasmic streaming during oogenesis, and Wash, a new subfamily of Wiskott-Aldrich Syndrome family proteins, that activates the Arp2/3 complex to nucleate branched actin filaments and functions to remodel actin structures and elicit changes in cell shape and movement.