Xiaozhu Huang received her medical degree from the Tongji Medical University in Wuhan, China. She came to UCSF in 1992 as a post-doctoral fellow and joined the faculty of the school of medicine in 1999. She is the director of the animal airway physiology and microscopy core facility, UCSF Sandler Certer for Basic Research in Asthma. Her major academic interests are in the areas of biological functions of integrins and genetic contributions of asthma.
My major research interest concerns biological functions
of integrins and molecular mechanisms of common lung diseases,
asthma, and pulmonary fibrosis. We have studied in vivo
functions of integrin avb6, avb5 and a9b1 using mice that
express null mutations of the molecules. b6 subunit knockout
mice develop exaggerated inflammatory responses to injury
in the lungs and skin, but are protected from bleomycin-induced
pulmonary fibrosis. Further study demonstrates the involvement
of b6 in the development of pulmonary emphysema. More
importantly, the phenotypes developed in b6 knockout mice
are mediated through binding and activating TGF-b pathway,
suggesting that our findings provide the possibility of
blocking TGF-b activation and thus of treating these diseases.
The studies on integrin subunit b5 using knockout mice
revealed important roles of this integrin in VEGF-mediated
vascular permeability and neovascularization. The studies
on a9 knockout mice provide evidence that this integrin
is important in lymphangiogenesis and angiogenesis.
I have been focusing on identifying new genes and gene
pathways that are involved in the pathogenesis of asthma.
Previous studies have shown that the development of asthma
is largely attributed to the interaction of genetic and
environmental factors. To better understand the genetic
factors that underlie the phenotypic features of asthma,
we have combined the strategy of genetic linkage analysis
and global analysis of gene expression in 11 different
inbred strains of mice in model of allergic asthma (ovalbumin
sensitization and challenge). Several candidate genes
have been shown to be associated with asthma-related features.
Of those, FcgammaRIIb is particular interesting to us
because this gene may be involved in regulating the function
of B lymphocyte and thus affects the serum IgE level at
least in mice. Further study of using transgenic and/or
knockout mice would help us to understand the specific
role(s) of each molecule in the model we have analyzed.
XZ Huang, JF Wu, D Cass, DJ Erle, D Corry, SG Young, RV Farese, Jr., and D Sheppard. Inactivation of the integrin b6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lungs and skin. J. Cell Biol. 1996; 133:921-928.
Huang XZ, Wu JF, Spong S, Sheppard D. The integrin avb6 is critical for keratinocyte migration on both its known ligand, fibronectin, and on vitronectin. J. Cell Sci. 1998; 111:2189-2195.
JS Munger, XZ Huang, H Kawakatsu, MJD Griffiths, SL Dalton, JF Wu, JF Pittet, N Kaminiski, C Garat, MA Matthay, DB Rifkin, D Sheppard. The integrin avb6 binds and activates latent TGFb1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 1999; 96:319-328.
Douglas a. Kuperman, Xiaozhu Huang, Laura l. Koth, Grace h. Chang, Gregory m. Dolganov, Zhou Zhu, Jack a. Elias, Dean Sheppard & David j. Erle Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nat Med. 2002 Aug; 8(8):885-9.
David G. Morris, Xiaozhu Huang, Naftali Kaminski, Yanli Wang, Steven D. Shapiro, Gregory Dolganov, Adam Glick, Dean Sheppard. Loss of integrin-mediated TGF activation causes Mmp12-dependent pulmonary emphysema. Nature. 2003, Mar; 13;422(6928):169-73