Faculty

Biochemistry and Molecular Genetics Faculty

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Contact Information

University Of Illinois at Chicago

Dept. Of Biochemistry and

Molecular Genetics

900 S. Ashland (M/C 669)
Chicago, IL 60607
tel: 312-996-7670
fax: 312-413-0353

Dr. Lester F. Lau

lflau@uic.edu

Major Interests:

Extracellular Matrix Signaling in Inflammation, Cancer, and Cardiovascular Development

The extracellular matrix plays critical roles in regulating diverse biological and pathological processes, including developmental morphogenesis, tissue repair and remodeling, inflammation and host defense, and progression of diseases such as cancer. Our laboratory is interested in the biological functions of CCNs, a family of cysteine-rich, dynamically expressed matricellular proteins that regulates a broad range of cellular activities through direct binding to cell surface integrin receptors and heparan sulfate proteoglycans. Ccn1- and Ccn2-null mice are embryonic and perinatal lethal due to cardiovascular and skeletal defects, respectively. Aberrant expression of Ccn1 is associated with pathological conditions including wound healing, atherosclerosis, restenosis, rheumatoid arthritis, and cancer. We are using biochemical and cell biological approaches to elucidate the functions of CCN1, complemented by in vivo studies using mouse models that genetically alter Ccn1 by targeted and conditional knockouts, allelic replacements, and transgenic expression.


	Dr. Lester. F. Lau, Professor PhD, Cornell University Postdoctoral Fellow, Johns Hopkins University School of Medicine

Inflammation and wound healing
We have shown that CCN1 can profoundly alter the activities of the tumor necrosis factor (TNF) family of cytokines, and polarize macrophages towards the classically activated M1 pathway that participates in Th1 responses. In addition, CCN1 is dynamically expressed at sites of inflammation and wound healing, suggesting a role in these contexts. Our recent studies showed that CCN1 can directly induce cellular senescence in fibroblasts, thereby triggering the expression of an anti-fibrotic genetic program. Furthermore, we showed that senescent cells accumulate as a healing response in murine cutaneous wounds and function to limit fibrosis, and these processes are dependent on CCN1. We are currently investigating the role and therapeutic potential of CCN1-induced senescence in the control of fibrosis and wound healing in animal models.

Cancer
Our laboratory has established that CCN proteins (CCN1, CCN2, and CCN3) are potent angiogenic inducers in vivo. The angiogenic activity of CCNs may play a critical role in the observed association of CCN expression in cancers of several tissues, including the breast, glia, and pancreas. We are analyzing the contribution of CCN1-regulated angiogenesis in tumor growth and metastasis

Cardiovascular Development
The significance of Ccn1 in cardiovascular development is demonstrated by the phenotypes of Ccn1-null mice, which suffer embryonic lethality due to impaired vessel bifurcation, loss of vessel integrity, and defective cardiac atrioventricular valvuoseptal morphogenesis. Heterozygous Ccn1 mice are largely viable, but exhibit ostium primum atrial septal defects. We are currently studying the roles of Ccn1 in cardiovascular development and cardiovascular diseases.

Recent Representative Publications:

Jun, J.I. and Lau, L.F. (2011) Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat. Rev. Drug Discov. 10:945-963. Abstract

Lau, L.F. (2011) CCN1/CYR61: the very model of a modern matricellular protein. Cell. Mol. Life Sci. 68:3149-3163. Abstract.

Jun, J.I. and Lau, L.F. (2010) The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat. Cell Biol. 12: 676-685. Abstract

Jun, J.I. and Lau, L.F. (2010) Cellular senescence controls fibrosis in wound healing. Aging (Albany NY) 2:627-631. Abstract

Bai, T., Chen, C.-C., and Lau, L.F. (2010) Matricellular protein CCN1 activates a proinflammatory genetic program in murine macrophages. J. Immunol. 184: 3223-3232. Abstract.

Franzen, C.A., Chen, C.-C., Todorovic, V., Juric, V., Monzon, R.I., and Lau, L.F. (2009) Matrix protein CCN1 is critical for prostate carcinoma cell proliferation and TRAIL-induced apoptosis. Mol. Cancer Res. 7: 1045-1055. Abstract

Juric, V., Chen, C.-C., and Lau, L.F. (2009) Fas-mediated apoptosis is regulated by the extracellular matrix protein CCN1 in vitro and in vivo. Mol. Cell. Biol. 29: 3266-3279. Abstract

List of Publications on PubMed

Laboratory Alumni:

Aleksandar M. Babic, M.D., Ph.D., Whitehead Institute

Ian J. Davis, M.D. Ph.D., University of North Carolina at Chapel Hill

Carrie Franzen, Ph.D., Northwestern University

Tatiana M. Grzeszkiewicz, M.D., Ph.D.,Palo Alto Medical Foundation

Thomas H. Hazel, Ph.D., Neuralstem, Inc.

Vladislava Juric, Ph.D., University of California at San Francisco

Maria L. Kireeva, Ph.D., National Cancer Institute

Branko V. Latinkic, Ph.D., Cardiff University, UK.

Shr-Jeng Leu, Ph.D., National Yang Ming University, Taiwan

Fan-E Mo, Ph.D., National Cheng Kung University, Taiwan