Arthur D. LanderProfessor and Chair, Developmental & Cell Biology |
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Research Interests |
growth factors; morphogenesis; extracellular matrix; transgenic and knockout mice; neural development and regeneration; cancer; systems biology; computational biology | |
| URL | lander-office.bio.uci.edu/landerfacts.html | |
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Academic Distinctions |
David and Lucile Packard Fellowship for Science and Engineering (1988) Javits Neuroscience Investigator Award (1998) American Society for Clinical Investigation (2000) |
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Research Abstract |
The Lander lab is interested in the molecular mechanisms by which cells communicate. We focus on two kinds of pathways--those involving growth factors and their receptors, and those involving molecules of the extracellular matrix and their receptors. We study these pathways in the context of both mammalian (mouse) development and cancer biology, since growth control and cell-matrix interactions are critical to both processes. We also focus on cells of the nervous system, to understand why the growth that occurs during developing often fails to recur after injury (e.g. spinal cord injury). We are able to work in such a wide range of areas by (1) emphasizing fundamental aspects of cellular communication that have broad applications, and (2) utilizing approaches such as transgenic and "knockout" mice, that enable the roles and effects of molecules to be studied in the context of an entire organism. One group of projects in the lab concerns "co-receptors", cell-surface molecules that regulate the interaction between soluble growth factors and their cell-surface receptors. We have identified a novel co-receptor for BMPs (bone morphogenetic proteins) and are studying the roles of Heparan Sulfate Proteoglycans (HSPGs) as co-receptors for a variety of growth factors, including those that drive tumor development and pattern the developing nervous system. We have used "knockout" technology to generate mice that are mutant for particular HSPGs, and are also working with mice that are mutant for some of the biosynthetic enzymes required to make HSPGs. We are also using modeling approaches to understand how HSPGs influences the kinetic parameters of growth factor-receptor interaction. Another area of investigation is the role of Chondroitin Sulfate Proteoglycans as scaffolding molecules that immobilize secreted signaling molecules. We study these in the developing brain, where they appear to play a role in localizing the molecules that \ guide growing axons. Another topic concerns a phenomenon called integrin activation, in which cells regulate the efficacy of their integrins, the major cells surface receptors for the extracellular matrix. We have obtained evidence that a decline in integrin activation accounts for some of the inability of mature central nervous system neurons to re-grow their axons after injury. We are using viral vectors to introduce genes into neurons of adult animals, in an attempt to reverse this decline. Patents: "Affinity Co-Electrophoresis" U.S. Patent No. 5,116,483, issued May 26, 1992. "Viral Inactivation Method and Apparatus" with T.P. Castor. U.S. Patent application filed March 1992. "Glypicans for the Detection and Treatment of Human Carcinoma" with M. Korc. U.S. Patent application filed October 1999. |
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| Publications | Lander, A.D., F.Y.M. Wan, H. Elledge, C. Mizutani, E. Bier and Q. Nie (200X) Diverse paths to morphogen gradient robustness. In revision. | |
| Kawauchi, S., R. Santos, M.E. Lopez-Burks, C.M. Young, M.P. Hoang, A. Chua, T. Lao, M.S. Lechner, L. Kitzes, B. Hallgrimsson, A.L. Calof and A.D. Lander (200X) Multiple organ system defects and transcriptional dysregulation in the Nipbl+/- mouse, a model of Cornelia de Lange Syndrome. Submitted | ||
| White, R.J., Q. Nie, A.D. Lander and T.F. Schilling (2007) Shaping the retinoic acid morphogen gradient in the zebrafish embryo by regulation of degradation. PloS Biology, 5, e304. | ||
| Zhang, Y.T., A.D. Lander and Q. Nie (2007) Computational analysis of BMP gradients in dorsal-vental patterning of the zebrafish embryo. J. Theor. Biol., 248, 579-589. | ||
| Lander, A.D. (2007) Morpheus Unbound: Re-imagining the Morphogen Gradient. Cell, 128, 245-256. | ||
| Lander, A.D., Q. Nie and F.Y.M. Wan (2006) Membrane associated non-receptors and morphogen gradients. Bulletin of Math Biology. 69, 33-54. | ||
| Lander, A.D., Q. Nie and F.Y.M. Wan (2006) Internalization and End Flux in Morphogen Gradient Formation. J. Computat. Appl. Math. 190, 232-251. | ||
| Ding, K., J. A., Sánchez-Duran, M. Korc, and A.D. Lander (2004) Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells. J. Cell Biol., submitted. | ||
| Murray, R.C., D. Navi, J. Fesenko, A.D. Lander, and A.L. Calof (2003) Widespread defects in the primary olfactory pathway caused by loss of MASH1 function. J. Neurosci. 23, 1769-1780 | ||
| Tsai, E.S., S. J. Haraldson, J. Baratta, A.D. Lander, J. Yu and R. T. Robertson (2002) Basal forebrain cholinergic cell attachment and neurite outgrowth on organotypic slice cultures of hippocampal formation, Neuroscience 115, 815-827. | ||
| Lander, A.D., Q. Nie and F.Y.-M. Wan (2002) Do morphogen gradients arise by diffusion? Developmental Cell 2, 785-796. | ||
| Matsuda, K., H. Maruyama, F. Guo, J. Kleeff, J. Itakura, Y. Matsumoto, A.D. Lander and M. Korc (2001) Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells. Cancer Research, 61, 5562-5569. | ||
| Karumanchi S.A., V. Jha , R. Ramchandran , A. Karihaloo , L. Tsiokas , B. Chan, M. Dhanabal, J.-i. Hanai, G. Venkataraman, Z. Shriver, N. Keiser, R. Kalluri, H. Zeng, D. Mukhopadhyay, R.L. Chen, A.D. Lander, K. Hagihara, Y. Yamaguchi, R. Sasisekharan, L. Cantley, and V. P. Sukhatme (2001) Cell Surface Glypicans Are Low-Affinity Endostatin Receptors. Molecular Cell 7, 811-822. | ||
| Chen, R.L. and A.D. Lander (2001) Mechanisms underlying preferential assembly of heparan sulfate on glypican-1. J. Biol. Chem. 276, 7507-7517. | ||
| Zhu, Z.-w., H. Friess, L. Wang, M. Abou-Shady, A. Zimmermann, A.D. Lander, M. Korc, J. Kleeff and M. Büchler (2001) Enhanced glypican-3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders. Gut 48, 558-64. | ||
| Emerling D.E., and A.D. Lander (2000) Using organotypic tissue slices as substrata for the culture of dissociated cells. Methods Mol Biol 139, 245-256. | ||
| Ivins J.K., P.D. Yurchenco, and A.D. Lander (2000) Regulation of neurite outgrowth by integrin activation. J. Neurosci. 20, 6551–6560. | ||
| Lander, A.D. and S. Selleck (2000) The elusive functions of proteoglycans: In vivo veritas. J. Cell Biol. 148, 227-232. | ||
| Kleef, J, T. Ishiwata, A. Kumbasar, H. Friess, M.W. Büchler, A.D. Lander and M. Korc (1998) The cell surface heparan sulfate proteoglycan glypican-1 is an essential regulator of growth factor action in pancreatic carcinoma cells, and is overexpressed in human pancreatic cancer. J. Clin. Invest. 102, 1662-1673. | ||
| Lander, A.D. (1998) Proteoglycans: Master regulators of molecular encounter? Matrix Biology 17, 465-472. | ||
| Emerling, D.E. and A.D. Lander (1996) Inhibitors and promoters of thalamic neuron adhesion and outgrowth in embryonic neocortex: functional association with chondroitin sulfate. Neuron, 17, 1089-1100. | ||
| Grants | NIH (NINDS) Analysis of Proteoglycans Involved in Brain Development | |
| NIH (NICHD) Co-Receptor Mechanisms in BMP Signaling | ||
| NIH (NIGMS) Morphogen Systems: A Joint Math and Experimental Initiative | ||
| NIH (NCI) Role of Glypicans in Pancreatic Cancer | ||
| Human Frontiers Science Program: Heparan sulfate proteoglycans in morphogen gradient formation | ||
| P50 - Systems Biology of Morphogenesis and Spatial Information Flow | ||
| HHMI - Howard Hughes Medical Institute through the HHMI-NIBIB Interfaces initiative - Mathematical, Computational, and Systems Biology | ||
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Professional Societies |
American Society for Cell Biology Society for Neuroscience Society for Developmental Biology American Society for Clinical Investigation American Society for Matrix Biology |
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| Other Experience |
Clinical Advisory Board Cornelia de Lange Syndrome Foundation 2002 |
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| Graduate Programs |
Cell Biology Cancer Biology Developmental Biology and Genetics Neurobiology |
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| Research Centers | Developmental Biology Center | |
| Cancer Research Institute | ||
| Center for Complex Biological Systems | ||
| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=2682 | |
| Last updated | 05/09/2008 | |