Faculty > Faculty By Appointment > Yina Huang, PhD
|Assistant Professor, Pathology and Immunology|
Office Suite C - 8417, BJCIH Building
Office: (314) 362-4708
Lab: (314) 362-4718
Pub Med Search
|My laboratory’s main interest is in identifying molecular mechanisms of lymphocyte activation and development. Using forward genetics, we have generated several lines of immunocompromised mice. With SNP analysis, these immunologic phenotypes are mapped to their causative genes for the purpose of discovering new genes or gene functions in the immune system.
In this manner, we have identified a mouse line that is deficient in ItpkB, a kinase that converts the Ca2+-regulating second messenger IP3 into IP4. Second messengers are critical for relaying signals that originate at the cell surface into the cell to induce normal cellular activation and differentiation but also transformation into tumor cells. Our studies demonstrate an independent role for IP4 as an important second messenger that is critical for lymphocyte development and activation. Soluble IP4 acts as an analog of the surface lipid, PIP3, which is generated by PI-3 kinase and turned over by the phosphatases PTEN and SHIP. PIP3 acts as a membrane ligand for a subset of Pleckstrin homology domain-containing proteins, thereby regulating their cellular localization and activity. As a PIP3 analog, IP4 potentially regulates any PIP3-binding protein, in either a positive or negative manner. We have previously demonstrated a positive role for IP4 in the activation of the Tec kinase, Itk. Using proteomics, our lab has identified many other IP4 binding proteins. An active area of investigation is determining how IP4 regulates their activity.
Disregulation of PIP3 levels can often lead to tumoriogenesis. As a potential signaling intermediate in the activation of PIP3-binding proteins, IP4 may play a critical role in cellular transformation. This possibility is currently being explored in the lab.
In a second mouse model, WeeT, we are genetically mapping the gene responsible for a different immunodeficiency. These mice have reduced peripheral T lymphocytes due to a migration defect from the thymus, where T cells develop. Detailed mechanistic analysis of these animals will provide insight into how lymphocytes traffic to survey the body for infections and antigenic challenge.
|Huang Y.H., Hoebe K., and K. Sauer.. New therapeutic targets in immune disorders: ItpkB, Orai1 and UNC93B.. Expert Opin Ther Targets. 12:391-413, 2008 Abstract|
|Huang, Y.H., J.A. Grasis, A.T. Miller, R. Xu, S. Soonthornvacharin, A.H. Andreotti, C.D. Tsoukas, M.P. Cooke, and K. Sauer.. Positive Regulation of Itk PH Domain Function by Soluble IP4.. Science 316:886-9, 2007 Abstract|
|Miller, A.T., M. Sandberg, Y.H. Huang, M. Young, S. Sutton, K. Sauer, and M.P. Cooke.. Production of Ins(1,3,4,5)P4 mediated by the kinase Itpkb inhibits store-operated calcium channels and regulates B cell selection and activation.. Nat. Immunol. 8:514-21., 2007 Abstract|
|Huang, Y.H., R. Barouch-Bentov, A. Herman, J. Walker and K. Sauer.. Integrating traditional and postgenomic approaches to investigate lymphocyte development and function.. Adv Exp Med Biol. 584:245-76., 2006 Abstract|
|Huang, Y.H., D. Li, T. Gee, A. Winoto and E.A.Robey.. Distinct transcriptional programs in thymocytes responding to T cell receptor, Notch, and positive selection signals.. Proc Natl Acad Sci USA. 101(14):4936-41., 2004 Abstract|
|DeLaire, S.*, Y.H. Huang*, S.W. Chan, and E.A. Robey.. Dynamic repositioning of CD4 and CD8 genes during T cell development.. J Exp Med. 200(11):1427-35., 2004 Abstract|