What We Do.

Organ Size Regulation

Despite fantastic progress in developmental biology research over the past decade, one aspect of development and tissue homeostasis for which very little is understood is how individual tissues reach and then maintain their appropriate size. Classic studies have demonstrated that tissues are able to “sense” their size and expand or shrink until a correct dimension has been reached. Nevertheless, the nature of the molecules and pathways involved in this process remains mysterious. Our laboratory utilizes a variety of genetic, biochemical, and high throughput technologies to identify molecules and mechanisms that regulate this fascinating process in mammals.

We are particularly interested in studying the function of an emerging highly-conserved developmental signaling cascade, the Hippo pathway, and its effects on tissue size, homeostasis and cancer. Our previous work has demonstrated that Hippo signaling can be a very potent regulator of organ size in mice and has also provided a conceptual link between organ size regulation and stem cell activity through Hippo signals. Our studies are now aimed at fully dissecting the components and the role of this cascade in somatic stem cells. For instance, we are currently performing genome-wide gain- and loss-of-function genetic screens to identify new regulators of Hippo signaling in mammals. Additionally, we have generated several animal models with mutations that can conditionally activate or deactivate Hippo signaling in our tissue of interest. These models will allow us to gain an understanding of the plethora of roles Hippo signaling plays during development, tissue regeneration, and malignancy. Insight into these processes will shed light on fundamental aspects of tissue regeneration and facilitate the development of therapeutic approaches based on cellular transplantation.

Characterization of hematopoietic stem cells in vivo

Our laboratory also has a strong interest in studying the cellular and molecular biology of hematopoietic stem cells. Our studies focus primarily on the in vivo roles of transcription factors and microRNAs in stem cell fate decisions, differentiation, and malignancy. Additionally, we have recently developed a novel methodology for the tracking and monitoring of individual hematopoietic stem cells and their progeny, which we think will evolve into an entirely novel experimental paradigm to study complex populations of stem cells in situ. This model will be an invaluable resource in the years to come to understand the behavior, dynamics and heterogeneity of stem cells in an array of disease conditions.