Research & Publications
The research in my laboratory focuses on the biology of signal transduction mediated by the intracellular protein kinase network such as the mitogen-activated protein kinase (MAPK) cascades and the mammalian target of rapamycine (mTOR) pathway in immune responses and in blood vessel function/development. We study the genes that encode either the serine/threonine kinases or their regulators in the kinase pathways. Our studies have revealed the roles of these kinase pathways in transducing various receptor signals and in regulating cell growth, differentiation, and apoptosis.
Extensive Research Description
The research in my laboratory focuses on the biology of signal transduction mediated by the intracellular protein kinase networks. We study the mitogen-activated protein kinase (MAPK) pathway and the mammalian target of rapamycine (mTOR) pathway. We wish to understand how these intracellular kinase pathways are utilized and regulated by immune system and cardiovascular system. Specifically, we want to reveal their specificity and physiological function in immune responses and in cardiovascular development and function.
We are also working to elucidate the underlying molecular mechanisms by which the kinase pathway-mediated receptor signaling regulates immune cell development, differentiation and effector function, as well as angiogenic signaling for cardiovascular development. Furthermore, we want to study the immune and inflammatory responses in the cardiovascular system and to determine how the MAPK pathway and the mTOR pathway are involved in these processes in physiological and pathological conditions.
To address the questions describe above, we have studied two Ser/Thr protein kinase molecules called MEKK2 and MEKK3 belonging to the MAP3K family in the MAPK pathway, and an adaptor molecule called Sin1, in the mTOR pathway. Thus far, my laboratory has generated knockout mice (both germline and conditional knockout) for these molecules to study their roles in the immune and cardiovascular systems. We have found that both MEKK2 and MEKK3 are key signaling molecules in the immune cells and endothelial cells, are required for multiple receptor-generated signals, and are also required for cellular stress responses.
We also demonstrated that Sin1 is a key regulator of the mTOR complex 2 (mTORC2) and is essential for Akt HM and TM site phosphorylation. Sin1-mTORC2 may also modify many other members of the AGC kinase family such as PKCs and SGK. We will continue to utilize a combination of biochemical and genetic approaches to study the regulation and physiological roles of MEKK2, MEKK3, and Sin1-mTOR signaling in immune and cardiovascular system.