Arthur D. Lander
Arthur D. Lander, M.D., Ph.D.
Director of Center for Complex Biological Systems & Professor
2638 Biological Sciences III
University of California Irvine
Irvine, CA 92697-2300
Tel: (949) 824-1721
Fax: (949) 824-1083
Website: Lab Homepage
Signaling & morphogenesis – 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.
- Chien, R., D.A. Newkirk, Y.-Y. Chen, W. Zeng, J. Biesinger, E. Flowers, N. Infante, S. Kawauchi, R. Santos, A.L. Calof, A.D. Lander, X. Xie and K. Yokomori (201X). The effect of Nipbl haploinsufficiency on genome-wide cohesin binding and gene expression. In preparation.
- Kunche, S., H. Yan, A.D. Lander, J.S. Lowengrub and A.L. Calof (201X) Feedback, lineages and de novo morphogenesis. In preparation for Physical Biology.
- Lo, W.C., S. Zhou, F.Y.M. Wan, A.D. Lander and Q. Nie (201X) Robust and Precise Morphogen-mediated Patterning: Tradeoffs, Constraints, and Mechanisms. In preparation.
- McHale, P. and A.D. Lander (201X) Role of symmetric stem cell divisions in delaying mutation accumulation. In preparation.
- Srinivasan, S., J.S. Hu, D.S. Currle, W.B. Hayes, A.D. Lander and E.S. Monuki (201X) Cell-intrinsic positive feedback driven by antagonistic extracellular signals as a basis for ultrasensitivity and developmental border formation. In revision.
- English, A.W., Y.-H. Jen, A. Mulligan, M.J. Sabatier, H. Saiyed, G. Schwartz, J. Spector, and A.D. Lander (200X) Axon regeneration after peripheral nerve injury is enhanced in syndecan and glypican knockout mice. In revision.
- Lander, A.D. (2013) How Cells Know Where They Are. Science. 339, 923-927.
- Konstorum, A., Sprowl, S.A., Lander, A.D., Waterman, M.L., Lowengrub, J.S. (2013) Elaboration of a multispecies model of solid tumor growth with tumor-host interactions. Proc. 3rd Int. Conf. Appl. Nonlinear Dynamics, Seattle, WA, Springer Verlag.
- Schilling T.F., Q. Nie and A.D. Lander (2012) Dynamics and precision in retinoic acid morphogen gradients. Curr Opin Genet Dev. doi:pii: S0959-437X(12)00142-6. 10.1016/j.gde.2012.11.012. [Epub ahead of print]. PMID: 23266215
- Palmer, R., J. McGeary, S. Francazio, A. Heath., A.D. Lander, B. Raphael, V. Knopik. (2012) The Genetics of Alcohol Dependence: Advancing Towards Systems-based Approaches. Drug and Alcohol Dependence, July 31. dx.doi.org/10.1016/j.drugalcdep.2012.07.005, Epub ahead of print. PMID:22854292. PMCID: PMC3470479
- Zhang, L., A.D. Lander and Q. Nie (2012) A reaction-diffusion mechanism influences cell lineage progression as a basis for formation, regeneration, and stability of intestinal crypts. BMC Systems Biology 6, 93. doi:10.1186/1752-0509-6-93. PMCID: PMC3434027
- Cai, A.Q., K. Radtke, A. Linville, A.D. Lander, Q. Nie, T.F. Schilling (2012) Cellular retinoic acid binding proteins (Crabps) are essential for hindbrain patterning and signal robustness in zebrafish. Development 139, 2150-2155. doi:10.1242/dev.077065. PMCID: PMC3357909
- Youssefpour, H., X. Li, A.D. Lander, and J. Lowengrub (2012) Multispecies model of cell lineages and feedback control in solid tumors. J. Theor. Biol. 304C:39-59. (Epub ahead of print). PMID: 22554945. PMCID: PMC3436435
- Kim, M.S., J.-R. Kim, D. Kim, A.D. Lander and K.-H. Cho (2012) Spatiotemporal network motif reveals the biological traits of developmental gene regulatory networks in Drosophila melanogaster BMC Systems Biol. 6, 31 doi:10.1186/1752-0509-6-31. PMCID: PMC3434043
- Zhou, S., W.-C. Lo, J. Suhalim, M. A Digman, E. Gratton, Q. Nie, and A. D. Lander (2012) Free extracellular diffusion creates the Dpp morphogen gradient of the Drosophila wing disc. Current Biology, 22, 668-675. DOI: 10.1016/j.cub.2012.02.065. PMCID: PMC3338872
- Lander A.D., J. Kimble, H. Clevers, E. Fuchs, D. Montarras, M. Buckingham, A.L Calof, A. Trumpp and T. Oskarsson (2012) What does the concept of the stem cell niche really mean today? BMC Biology, 10, 19. PMCID: PMC3298504
- Muto, A., A.L.Calof, A.D. Lander and T.F. Schilling (2011) Multifactorial origins of heart and gut defects in nipbl-deficient zebrafish, a model of Cornelia de Lange Syndrome. PLoS Biology, 9, e1001181. PMCID: PMC3201921
- Nahmad, M and A.D. Lander (2011) Spatiotemporal mechanisms of morphogen gradient interpretation. Curr. Opin. Genet. Devel. 21, 726-31. PMCID: PMC3423890
- Gokoffski, K.K., H.-H. Wu, C.L. Beites, J. Kim, E.J. Kim, M.M. Matzuk, J.E. Johnson, A.D. Lander and A.L. Calof (2011) Activin and GDF11 collaborate in feedback control of neuroepithelial stem cell proliferation and fate. Development, 138, 4131-4142. doi:10.1242/dev.065870. PMCID: PMC3171217
- Lei, J., F.Y.M. Wan, A.D. Lander and Q. Nie (2011) Robustness of signaling gradient in Drosophila wing imaginal disc. Discrete & Continuous Dynamical Systems Series B, 16(3), 835 – 866. doi:10.3934/dcdsb.2011.16.835 (Winner, 2011 DCDS-B Best Paper Award).
- Lander, A.D., Q. Nie, B. Vargas and F.Y.M. Wan (2011) Size-normalized robustness of Dpp gradient in Drosophila wing imaginal disc. J. Mechanics of Materials and Structures, 6, 321-350. PMCID: PMC3154743
- Lander, A.D. (2011) The individuality of stem cells. BMC Biol, 9, 40. doi:10.1186/1741-7007-9-40. PMCID: PMC3110137
- Chien, R., W. Zeng, S. Kawauchi, M.A. Bender, R. Santos, H.C. Gregson, J.A. Schmiesing, D. Newkirk, X. Kong, A.R. Ball Jr., A.L. Calof, A.D. Lander, M Groudine and K. Yokomori (2011) Cohesin mediates chromatin interactions that regulate mammalian b-globin expression. J. Biol. Chem., 286, 17870-17878. doi/10.1074/jbc.M110.207365. PMCID: PMC3093862
- Lander, A.D. (2011) Pattern, growth and control. Cell 144, 955-969. PMCID: PMC3128888
- Chou, C.S., W.-C. Lo, K. K. Gokoffski, Y.-T. Zhang, F.Y.M. Wan, A. D. Lander, A. L. Calof, and Q. Nie (2010) Spatial dynamics of multi-stage cell lineages in tissue stratification. Biophys. J., 99, 3145-3154. PMCID: PMC2980753
- Kuo, W.-J., M. Digman and A.D. Lander (2010) Heparan sulfate acts as a BMP co-receptor by facilitating ligand-induced receptor hetero-oligomerization. Mol. Biol. Cell 21, 4028-4041. doi 10.1091/mbc.E10-04-0348. PMCID: PMC2982130
- Potkin, S. G., F. Macciardi, M. Vawter, G. Guffanti, Q. Wang, J.A. Turner, A. Lakatos, M.F. Miles, A. Lander, and X. Xie (2010) Identifying Gene Regulatory Networks in Schizophrenia. Neuroimage 53, 839-847. PMCID: PMC3055795
- Lander, A.D. (2010) The edges of understanding. BMC Biol. 8: 40doi:10.1186/1741-7007-8-40. PMCID: PMC2864098
- Gokoffski, K.K., Kawauchi, S., H.-H. Wu, R. Santos, P.W.L. Hollenbeck, A.D. Lander and A.L. Calof (2009) Feedback regulation of neurogenesis in the mammalian olfactory epithelium: New insights from genetics and systems biology. In: Neurobiology of Olfaction, A. Menini, Ed. CRC press, In press.
- Lander, A.D. (2009) The “stem cell” concept: is it holding us back? J. Biol. 8, 70. doi:10.1186/jbiol177
- Liu, J., M.B. Dillencourt, L.F. Bic, D. Gillen and A.D. Lander (2009) Distributed Individual-Based Simulation. In: Euro-Par 2009—Parallel Processing: Proceedings of the 15th International European Conference on Parallel and Distributed Computing, Lecture Notes in Computer Science, vol. 5704. H. Sips, D. Epema and H-X. Lin, Eds. Springer, Heidelberg. pp590-601. doi:10.1007/978-3-642-03869-3_56
- Jen, Y-H, M. Musacchio and A.D. Lander (2009) Glypican-1 controls brain size through regulation of FGF signaling in early neurogenesis. Neural Development, 4:33, doi:10.1186/1749-8104-4-33
- Lander, A.D., W.-C. Lo, Q. Nie and F.Y.M. Wan (2009) The measure of success: constraints, objectives and tradeoffs in morphogen-mediated patterning. Cold Spring Harbor Perspectives in Biology 1, a002022: doi: 10.1101/cshperspect.a002022.
- Lander, A.D., Q. Nie, F.Y.M. Wan, and Y.-T. Zhang (2009) Localized Ectopic Expression of Dpp Receptors in a Drosophila Embryo. Studies in Applied Mathematics, 123, doi: 10.1111/j.1467-9590.2009.00450.x.
- Beites, C.L., P.L.W. Hollenbeck, J. Kim1, R. Lovell-Badge, A.D. Lander and A.L. Calof 1 (2009) Follistatin modulates a BMP autoregulatory loop to control size and patterning of sensory domains in developing tongue. Development,136 (13):2187-2197
- Kawauchi, S., J. Kim, R. Santos, H.-H. Wu, A.D. Lander and A.L. Calof (2009) Foxg1 promotes olfactory neurogenesis by antagonizing Gdf11. Development 136, 1453-1464.
- Lander, A.D., K. K. Gokoffski, Frederic Y. M. Wan, Qing Nie and Anne L. Calof (2009) Cell Lineages and the Logic of Proliferative Control. PLoS Biology 7, e15:doi:10.1371/journal.pbio.1000015.
- Lo, W.-C., C.S. Chou, K.K. Gokoffski, F.Y.M. Wan, A.D. Lander, A.L. Calof and Q. Nie (2009) Feedback regulation in multistage cell lineages. Math Biosci Eng., 6, 59-82.
- Whipple C.A., A.D. Lander and M. Korc (2008) Discovery of a novel molecule that regulates tumor growth and metastasis. ScientificWorldJournal 8,1250-1253.
- Aikawa, T, C. Whipple, M.E. Lopez, J. Gunn, A. Young, A.D. Lander and M. Korc (2007) Glypican-1 modulates the angiogenic and metastatic potential of human and mouse cancer cells. J Clin. Invest. 118, 89-99.
- White, R.J., Q. Nie, A.D. Lander and T.F. Schilling (2007) Complex regulation of cyp26a1 creates a robust retinoic acid gradient in the zebrafish embryo. PLoS Biology, 5, e304.
- Lander, A.D., Q. Nie and F.Y.M. Wan (2007) Membrane associated non-receptors and morphogen gradients. Bulletin of Math. Biol. 69, 33-54. DOI: 10.1007/s11538-006-9152-2.
- Lander, A.D. (2007) Morpheus Unbound: Re-imagining the Morphogen Gradient. Cell, 128, 245-256.
- 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
- 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.
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