K. H. William Lau, PhD Research Professor
Musculoskeletal Disease Center
Jerry L. Pettis Memorial VA Medical Center
11201 Benton Street
Loma Linda, CA 92357
Phone: (909) 825-7084, extension 2836
Fax: (909) 796-1680
Email: William.Lau@med.va.gov
Our laboratory currently has three areas of research interest. First, we are interested in dissecting the signal transduction pathways in osteoblasts and osteoclasts responsible for the regulation of bone formation and resorption, respectively, particularly those involving protein-tyrosine phosphatases. At the present time, we are focused on signaling pathways mediated by three protein-tyrosine phosphatases: 1) an osteoclastic protein-tyrosine phosphatase, PTP-oc; 2) the protein-tyrosine phosphatase, SHP-1, in osteoclasts; and 3) an osteoblastic fluoride-sensitive, tartrate-resistant, protein-tyrosine phosphatase. Information derived from these studies not only provides mechanistic insights into the regulation of bone formation and resorption by osteoblasts and osteoclasts respectively but also provides novel targets for development of effective drugs for bone wasting diseases such as osteoporosis.
The second area of our current research interest is to dissect the underlying molecular mechanisms of the regulation of bone formation by mechanical loading. Mechanical loading produces strains in the bone that generate interstitial fluid flow through the lacunar-canalicular spaces. It is believed that this fluid flow exerts a shear stress at surfaces of bone cells lining the lacunar-canalicular spaces, and that the shear stress then generates biochemical signals that transduced to the nucleus of bone cells to stimulate osteoblast proliferation and activity. Accordingly, our work uses fluid shear stress created in a flow chamber with osteoblasts as an in vitro model to dissect mechanotransduction pathways.
The third area of research interest our laboratory relates to development of effective gene therapy protocols for the musculoskeletal system. Our current approaches involve the use of viral and plasmid vectors to increase endosteal bone formation and to heal bone fractures.
Koyama H, Nakade O, Takada Y, Kaku T, and Lau K-HW. Melatonin, at pharmacologic doses, increases bone mass in mice by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Miner Res 2002 Jul;17(7):1219-1229.
Harris JW, Strong DD, Amoui M, Baylink DJ, and Lau K-HW . Construction of a Tc1-like transposon Sleeping Beauty-based gene transfer plasmid vector for generation of stable transgenic mammalian cell clones. Anal Biochem 2002 Nov 1;310(1):15-26.
Kapur S, Baylink DJ, and Lau K-HW . Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. Bone 2003 Mar;32(3):241-251.
Rundle CH, Miyakoshi N, Kasukawa Y, Chen S-T, Sheng MH-C, Wergedal JE, Lau K-HW, and Baylink DJ. In vivo bone formation in fracture repair induced by direct retroviral-based gene therapy with BMP-4. Bone2003 Jun;32(6):591-601.
Lau K-HW and Baylink DJ. Osteoblastic tartrate-resistant acid phosphatase: its potential role in the molecular mechanism of osteogenic action of fluoride. J Bone Miner Res 2003 Oct;18(10):1897-1900.
Amoui M, Baylink DJ, Tillman JB, and Lau K-HW . Expression of a structurally unique osteoclastic protein-tyrosine phosphatase is driven by an alternative intronic, cell-type-specific promoter. J Biol Chem 2003 Nov 7;278(45):44273-44280.
Zhang XS, Linkhart TA, Chen S-T, Peng H, Wergedal JE, Guttierez GG, Sheng MH-C, Lau K-HW, and Baylink DJ. Local ex vivo gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in mice. J Gene Med 2004 Jan;6(1):4-15.
Klamut HJ, Chen S-T, Lau K-HW, and Baylink DJ. Crit Rev Eukaryotic Gene Expression 2004;14(1-2):89-136..
Kapur S, Chen S-T, Baylink DJ, and Lau K-HW . Extracellular signal-regulated kinase-1 and -2 are both essential for the shear stress-induced human osteoblast proliferation. Bone 2004 Aug;35(2):525-534.
Amoui M, Suhr SM, Baylink DJ, and Lau K-HW . An osteoclastic protein-tyrosine phosphatase may play a role in the differentiation and activity of human monocytic U-937 cell-derived, osteoclast-like cells. Am J Physiol Cell Physiol 2004 Oct;287(4):C874-C884.
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Last Revised: Tue, Jul 11, 2006