In multicellular organisms, each cell is programmed to respond to a number of extracellular signals, such as hormones, cytokines, and growth factors. In most cases, these signals are transmitted from “outside” to “inside” of the cell via their specific cell-surface receptors to regulate cell behavior and function. The important cell processes such as cell proliferation, differentiation, and apoptosis (programmed cell death), are profoundly regulated by cell signaling. Dysfunction of cell signaling has been associated with the origin and development of many diseases such as diabetes and cancer. Thus, to gain insights into cell signaling is fundamental to the in-depth understanding of the nature of diseases. This research may eventually lead to the discovery of non-invasive biomarkers for early detection and development of novel, effective therapeutic interventions.
Laboratory Research Goal
Despite extensive studies in the past, the cell signaling pathways, in particular, their crosstalk that integrates and diversifies signaling are still poorly understood. The research goal of our laboratory is to clarify the molecular foundations for cell signaling in regulating cell behavior and function. We are particularly interested in signaling crosstalk mediated by epidermal growth factor (EGF), insulin-like growth factor (IGF-1) and cell adhesion molecules, and the effects of such crosstalk on cell adhesion, migration, differentiation, growth and survival. Our research may have important implications in endocrine-related diseases including gynecologic cancer, endometriosis and diabetes.
The PI has recently received several awards from Science Foundation Arizona (SFAz), American Heart Association (AHA), Arizona Biomedical Research Commission (ABRC), and other national and international research funding agencies. The PI had the following major accomplishments in the field of cell signaling research in the past.
- Discovered the essential roles of a focal adhesion protein, integrin-linked kinase (ILK), in regulating muscle cell differentiation (Huang et al., J Cell Biol 2000, 150: 861);
- Identified a novel focal adhesion protein that interacts with integrin-linked kinase (ILK) and is critically involved in the regulation of cell adhesion and spreading (Tu et al., J Cell Biol 2001, 153: 585);
- Characterized the physical and functional interaction of GH and IGF-1 signaling elements in mouse preadipocytes (Huang et al., Mol Endocrinol 2004, 18: 1471);
- Uncovered a previously unappreciated mechanism by which GH affects the EGF signaling in mouse preadipocytes (Huang et al., J Biol Chem 2003, 278: 18902; Huang et al., Endocrinology 2004, 145: 3297);
- Uncovered the mechanism by which prolactin modulates phosphorylation, signaling, and trafficking of EGFR in human T47D breast cancer cells (Huang et al., Oncogene 2006, 25: 7565).
- Identified a novel endothelial cell-specific molecule, which can localize to cell-cell junctions and modulate actin cytoskeletal remodeling, growth factor receptor signaling, and cell migration (Ma et al., Genes Cells 2009, 14: 281; Shi et al., PLoS ONE 2011, 6(6): e21482).
- Recent discovery of differential roles of ERK and AKT in EGFR-mediated signaling and cell motility in prostate cancer cells (Gan et al., Oncogene 2010, 29: 4947);
- Recent discovery of the critical role of GH and IGF-1 signaling crosstalk in the regulation of pancreatic islet beta-cell function (Ma et al., Mol Endocrinol 2011, 25: 2119).
Research (Basic and Translational Projects)
- Signaling crosstalk between insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF) in breast and prostate cancer
- Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) signaling in pancreatic islet beta-cells: potential roles in obesity-linked type 2 diabetes
- Adiponectin and leptin in human umbilical cord blood: potential roles in fetal growth and development and implications in metabolic diseases (Co-investigators: Drs. J. Balducci, R. Blumrick, and L. Chambliss)
- Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) signaling in endometrial cancer and endometriosis (Co-investigator: Dr. M. Hibner)
- Potential roles of endothelial cell-specific molecules in angiogenesis-related diseases (Co-investigators: Drs. M. Hibner and I. Benjamin)
- Identification of specific protein expression and modification patterns in different forms of endometriosis by proteomic analysis (Co-investigator: Dr. M. Hibner)
- Development of antibodies for non-invasive detection of endometriosis (Co-investigator: Dr. M. Hibner)
- Signal pathway underlies GABAA receptor-mediated excitation in human hypothalamic hamartomas (Co-PI: Dr. J. Wu at Barrow Neurological Institute).
Yao (Joyce) Huang, PhD
Assistant Staff Scientist
Director, Laboratory of Signal Transduction
Division of Obstetrics and Gynecology
St. Joseph’s Hospital and Medical Center
Phoenix, Arizona, USA