Bone morphogenetic protein (BMP) signaling plays a major role in embryonic development and adult tissue homeostasis. Aberrations in BMP signaling lead to congenital anomalies, cardiovascular diseases and certain type of cancers. BMP receptors signal in response to a variety of bound BMP ligands. Our investigations show that endocytosis is pivotal for BMP receptor signaling and dorsoventral axis patterning in developing embryos. But how BMP receptors are internalized and transported through different intracellular compartments, how they interact with effectors and regulators and how it leads to regulation of signaling and ultimately to dorsoventral patterning events remain elusive. In this project, we seek to address these questions by using optically transparent zebrafish embryos. Ultimately, the cues obtained from this study will be used to identify novel therapeutic targets for diseases associated with aberrant BMP signaling.

Cholesterol is a vital nutrient for all cells in our body. Most of the cells in our body internalize cholesterol as low density lipoprotein (LDL) from circulation. LDL is enzymatically dissociated to free cholesterol inside lysosomes which is then transported to other organelles. Recent findings in our lab and other labs reveal that cholesterol facilitates recruitment and activation of mTOR signaling complex on lysosomes leading to cell growth. Currently, we are investigating the molecular mechanisms underpinning cholesterol sensing and mTOR activation on lysosomes. We are also trying to understand how this process goes awry in certain cancers and other cholesterol- associated metabolic, neurological and infectious diseases. Using a variety of cell lines and model organisms, a long term goal is to discover novel approaches to maintain cholesterol homeostasis in various physiological and pathological conditions.