Research
Interests
My
laboratory is interested in understanding how blood vessels
develop during embryogenesis and repair themselves following
vascular injury. We have recently focused on the family of
Notch receptors, which have been shown to be highly expressed
in large vessels during remodeling. Our goals are to understand
the pathways by which Notch receptor signaling controls smooth
muscle cell and endothelial cell behavior. These studies apply
to human diseases including restenosis, atherosclerosis, and
other vascular obstructive diseases. In addition, blood vessel
recruitment and growth is a hallmark of successful tumors,
and we are interested in signals that increase tumor cell growth
and survival.
One
of our major strategies is to create murine genetic transgenic
models in which we can activate or inhibit Notch receptor signaling
in a vascular-specific manner. These models will allow us to
develop in vivo systems to understand blood vessel remodeling
and tumor growth.
I also direct the Mouse Transgenic Core Facility, which is a resource for the generation of mouse transgenics and gene targeted models. This service allows
investigators to submit transgenes of interest for pronuclear
injection to obtain transgenic animals, or target specific
genes in embryonic stem cells. Other resources available through
this Core Facility are cryoprotection of mouse lines, re-derivation,
embryo staging and collection, and maintenance of shared strains
for investigator use. |
Selected
Publications
Venatesh DA, Park S-K, Harrington A, Miceli-Libby L, Yoon JE, Liaw L. Cardiovascular and hematopoietic defects associated with Notch1 activation in embryonic Tie2 expressing populations. Circ. Res. 2008, in press, ePub July 2008.
Urs S, Roudabush A, O’Neill CF, Pinz I, Prudovsky I, Kacer D, Liaw L, Small D. Soluble forms of the Notch ligands Delta1 and Jagged1 promote in vivo tumorigenicity in NIH3T3 fibroblasts with distinct phenotypes. Am. J. Pathol. 2008, in press.
Tang Y, Urs S, Liaw L: Hairy-related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by interfering with Notch intracellular domain/CBF-1 complex interaction with the CBF-1 binding site. Circ. Res. 2008 102:661-668.
Plumer A, Duan H, Subramaniam S, Lucas FL, Miesfeldt S, Ng AK, Liaw L: Development of fragment-specific osteopontin antibodies and ELISA for quantification in human metastatic breast cancer. BMC Cancer 2008, 8:38.
Miceli-Libby L, Johnson MJ, Harrington A, Hara-Kaonga B, Ng A-K, Liaw L: Widespread Delta-like-1 expression in normal adult mouse tissue and injured endothelium is reflected by expression of the Dll1LacZ locus. J. Vasc. Res. 2007, 45:1-9.
O’Neill CF, Urs S, Cinelli C, Lincoln A, Nadeau RJ, Leon R, Toher J, Mouta-Bellum C, Friesel RE, Liaw L: Notch2 signaling induces apoptosis and inhibits human MDA-MB-231 xenograft growth. Am. J. Pathol 2007;171:1023-1036.
Urs S, Harrington A, Liaw L*, Small D*: Selective expression of an aP2/fatty acid binding protein4-Cre transgene in non-adipogenic tissues during embryonic development. Transgenic Research 2006;15:647-653. *equal contribution from these authors
Havrda MC, Johnson MJ, O’Neill CF, Liaw L: A novel mechanism of transcriptional repression of p27kip1 through Notch/HRT2 signaling in vascular smooth muscle cells. Thrombosis and Haemostasis 2006;96:361-370.
Hara-Kaonga B, Gao YA, Havrda M, Harrington A, Bergquist I, Liaw L: Variable recombination efficiency in responder transgenes activated by Cre recombinase in the vasculature. Transgenic Res 2006; 15:101-106. |
