Epigenetic gene regulation plays crucial and indispensable roles by control of spatiotemporal gene expression essential for progenitor cell self-renewal, differentiation, key processes for patterning and morphogenesis during organismal development and their misregulation in disease. Research in Kota Lab is focused on elucidation of epigenetic players and their targets in progenitor cells during embryonic and postnatal development using ES cells, primary cultures of progenitor cells and mouse models.

Current Projects
We are investigating

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Funder(s): NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

In this study, we pursue our research on the molecular mechanisms of the differentiation of osteoclasts and bone resorption. The understanding osteoclast (OC) differentiation and activity has been revolutionized by the discovery that (1) the activation of RANK by RANK ligand is absolutely required for osteoclast formation and activity, and (2) stimulation of myelomonocytic precursors with M-CSF and RANK ligand is sufficient to induce the formation of OCs. Less publicized, but...

Funder(s): NIH/NIAMS

Bone morphogenetic proteins (BMPs) were identified as potent bone forming agents based on their ability to induce de novo bone formation in adult animals and this unique feature of BMP activity has led to use of BMPs as therapeutic agents in bone repair. It has also generated intense interest in defining the role endogenous BMPs play in the skeleton. Removal of individual osteogenic BMPs (BMPs 2, 4, 5, 6, 7) during embryonic development shows that loss of any individual BMP can be compensated for by the other BMPs present. Mice in which...

Funder(s): NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Bone resorption is performed by the mature osteoclast. To resorb bone, osteoclasts require both the presence of dynamic actin adhesion structures in the sealing zone (podosomes) and very efficient endocytosis in the ruffled-border domain. Data generated in our laboratory within the last five years has clearly established that two signaling enzyme activities are directly involved in the regulation of both bone resorption and actin dynamics in the osteoclast. On the one hand, we have shown...

Funder(s): NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Calcitonin (CT) is the most potent and rapidly acting known inhibitor of bone resorption that targets the osteoclast (OC) directly. CT was the first therapeutic agent used to inhibit excessive bone resorption in osteoporosis and other conditions. It is still used, and new formulations for treating osteoarthritis and osteoporosis are currently in development, despite the fact that a reported loss of efficacy with time has somewhat limited clinical use. Thus, new information about the...