Yingqun Huang PhD, MD
Associate Professor of Obstetrics, Gynecology, and Reproductive Sciences
RNA biology; Stem cells; Post-transcriptional regulation of gene expression; Cancer biology
Dr. Huang’s most significant research contributions are related to identification and elucidation of the role of antigen-presenting cells (APCs), including macrophages (Mfs) and dendritic cells (DCs), in the pathogenesis of preeclampsia (PE). APCs of innate immunity act as the first line defense, which in turn present antigens to adaptive immunity in response to pathogens. PE is suggested to result from immune maladaptation.
Dr. Huang’s early studies were first to identify an elevation of Mfs, immature and mature DCs as well as their recruiting-chemokines in preeclamptic decidua. To elucidate the mechanism of APC recruitment and its role during the pathogenesis of PE, Dr. Huang conducted in vitro studies using inflammatory cytokine-treated first trimester decidua cells. Dr. Huang demonstrated that an array of colony stimulating factors and APC-recruiting chemokines were up-regulated by IL-1b or TNF-a in first trimester decidual cells that led to an enhancement of Mf and DC chemotaxis.
Extensive Research Description
My laboratory is interested in the molecular function of Lin28 in mouse and human embyronic stem (ES) cells. Lin28 is an evolutionarily conserved RNA-binding protein originally identified as a key regulator of developmental timing in the nematodes C. elegans. As a well-accepted ES cell marker, Lin28 is among four factors (including Oct4, Sox2 and Nanog) that together reprogram human fibroblasts to pluripo-tency. Despite its apparent critical role in ES cells, the molecular function and mode of action of Lin28 are just beginning to be elucidated. Multiple studies have demonstrated that Lin28 functions to block the pro-duction of mature let-7 microRNAs implicated in the regulation of cell growth and differentiation. In addi-tion, let-7 microRNAs repress the expression of Lin28, creating a feedback loop.
However, other evidence exists that Lin28 may regulate gene expression through multiple mechanisms. Indeed, Lin28 has been re-ported to be associated with ribonucleoprotein particles (RNPs) containing IGF-2 mRNA and to stimulate its translation in muscle cells. Similarly, recent studies from my group suggest that Lin28 acts to modulate mouse ES cell growth likely in part by effecting the expression of cell cycle genes at the translational level. Thus, a major role Lin28 may play in ES cells is to regulate the expression of genes involved in cell cycle progression. This is conceivable given that pluripotency is believed to be mechanistically linked to the unique proliferative properties of ES cells.
Our current studies focus on the further dissection of the molecular mechanisms and pathways involved in Lin28-mediated regulation. First, we will analyze Lin28 expression in mouse and human ES cells to determine whether its expression is regulated during the cell cy-cle. Then, we will characterize the interactions between Lin28 and its associated mRNAs to gain molecular insights into their assembly, function and regulation in the cellular milieu. Finally, we will strive to identify Lin28-interacting protein partners and new target mRNAs to establish a comprehensive and global under-standing of Lin28 function.