Arthur D. Lander, M.D., Ph.D.

Arthur D. Lander

Research in the Lander lab is focused on the Systems Biology of Development and Disease, and deals with topics in Developmental Biology, Cell Biology, Mathematical/Computational Biology, Glycobiology, Neurobiology, Cancer Biology and Engineering.  The lab is interested in the control of cellular behaviors, with the word control used in its engineering sense: the execution of strategies for achieving useful ends, such as precision, robustness, efficiency and fast response. Biological development and regeneration provide impressive examples of tight control of growth, differentiation and patterning. Numerous developmental processes have been extensively studied from a mechanistic perspective (What happens? What molecules are involved? How do they work?), but only recently have serious efforts been directed toward understanding the logic of control (Why is the system configured the way it is? What purpose does it serve?).

The Lander lab seeks to address control questions in the context of long-standing biological problems in the areas of pattern formation, growth regulation and regeneration.  They using a variety of traditional biology approaches:  model organisms (mice, flies, fish), genetic manipulation, and genomic analysis, but because control problems are inherently systems-level–i.e. they deal with the behavior of an entire system in its environment– the tools of  Systems Biology play a critical role in the lab’s research, including mathematical modeling, computational simulation, large-scale data collection, and high-resolution live cell imaging. To facilitate this,  collaborates with mathematicians, computer scientists, physicists and engineers play an important role in the lab’s research.

Some of the specific focus areas of the lab include:

Morphogen gradients and their role in pattern formation

Proliferative Control in Development and Cancer

“Transcriptomopathies” and the multifactorial origins of birth defects. 

The evolution of combinatorial fragility.

For more information, see the lab website

Recent Publications

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

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

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

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. 304:39-59. PMID: 22554945. PMCID: PMC3436435

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

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

Schilling T.F., Q. Nie and A.D. Lander (2012) Dynamics and precision in retinoic acid morphogen gradients. Curr Opin Genet Dev. 22:562-569. doi:pii: S0959-437X(12)00142-6. 10.1016/j.gde.2012.11.012. PMID: 23266215. NIHMS430584.

Lander, A.D. (2013) How Cells Know Where They Are. Science. 339, 923-927. PMID: 23430648

S. Remeseiro, A. Cuadrado, S. Kawauchi, A.L. Calof, A.D. Lander and A. Losada (2013) Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange Syndrome. Biochim Biophys Acta 1832, 2097-102. doi: 10.1016/j.bbadis.2013.07.020. PMCID: PMC3825806

Visnes, T., F. Giordano, A. Kuznetsova, JA Suja, A.D. Lander, A.L. Calof and L. Stršm (2013) Localization of the SMC-loading complex Nipbl/Mau2 during mammalian meiotic prophase I. Chromosoma, 123, 239-252. PMID: 24287868; PMCID: PMC4031387.

Konstorum A., S.A. Sprowl, M.L. Waterman, A.D. Lander, and J. Lowengrub (2014) Predicting mechanism of biphasic growth factor action on tumor growth using a multi-species model with feedback control. J. Coupled Systems and Multiscale Dynamics, 1, 459-467.

Srinivasan, S., J.S. Hu, D.S. Currle, E.S. Fung, W.B. Hayes, A.D. Lander and E.S. Monuki (2014) A BMP-FGF Morphogen Toggle Switch Drives the Ultrasensitive Expression of Multiple Genes in the Developing Forebrain. PLoS Computational Biol 10, e1003463. doi:10.1371/journal.pcbi.1003463. PMID: 24550718, PMCID: PMC3923663.

McHale, P. and A.D. Lander (2014) The Protective Role of Symmetric Stem Cell Division on the Accumulation of Heritable Damage. PLoS Computational Biology Aug 14;10(8):e1003802. doi: 10.1371/journal.pcbi.1003802. PMID: 25121484, PMCID: PMC4133021

Lander A.D. (2014) Making sense in biology: An appreciation of Julian Lewis. BMC Biology 12, 57. doi:10.1186/s12915-014-0057-5

Muto, A., S. Ikeda, M.E. Lopez-Burks, Y Kikuchi, A.L. Calof, A.D. Lander and T.F. Schilling (2014) Nipbl and Mediator Cooperatively Regulate Gene Expression to Control Limb Development. PLoS Genetics, 10(9):e1004671. doi: 10.1371/journal.pgen.1004671.

Lo, W-C, S. Zhou, F.Y.M. Wan, A.D. Lander and Q. Nie (2015) Robust and Precise Morphogen-mediated Patterning: Tradeoffs, Constraints, and Mechanisms. J. Royal Soc. Interface. 12, 20141041. DOI: 10.1098/rsif.2014.1041.

Buzi, G., Lander, A.D., and Khammash, M. (2015). Cell lineage branching as a strategy for proliferative control. BMC Biology, 13, 13. doi:10.1186/s12915-015-0122-8.

Chen C.C., Wang L., Murray P.J., Jiang T.X., Plkus M.V., Lee O., Shi S., Widelitz R.B., Lander A.D. and Chuong C.M. (2015) Organ-level quorum sensing directs regeneration in hair stem cell populations. Cell 161, 277-290. dos: 10.1016/j.cell.2015.02.016.

Kunche, S., H. Yan, A.L. Calof, J.S. Lowengrub and A.D. Lander (2016) Feedback, lineages and self-organized morphogenesis. PLoS Computational Biol, 12, e1004814. doi:10.1371/journal.pcbi.1004814.

Wilkins, J.F., P.T. McHale, J. Gervin and A.D. Lander (2016) Survival of the Curviest: Noise-Driven Selection for Synergistic Epistasis. PLoS Genetics 12(4): e1006003. doi:10.1371/journal.pgen.1006003

Lopez-Burks, M.E., R. Santos, S. Kawauchi, A.L. Calof and A.D. Lander (2016) Genetic enhancement of limb defects in a mouse model of Cornelia de Lange Syndrome. Am J Med Genet C Semin Med Genet. 2016 Jun;172(2):146-54. doi: 10.1002/ajmg.c.31491.

Kawauchi, S., R. Santos, A. Muto, M.E. Lopez-Burks, T.F. Schilling, A.D. Lander and A.L. Calof (2016) Using Mouse and Zebrafish Models to Understand the Etiology of Developmental Defects in Cornelia de Lange Syndrome. Am J Med Genet C Semin Med Genet. 2016 Jun;172(2):138-45. doi: 10.1002/ajmg.c.31484. PMID: 27120001.

Santos R., S. Kawauchi, R.E. Jacobs, M.E. Lopez-Burks, H. Choi, J. Wikenheiser, B. Hallgrimsson, H.A. Jamniczky, S.E. Fraser, A.D. Lander, and A.L. Calof (201X) Conditional creation and rescue of Nipbl-deficiency in mice reveals multiple determinants of risk for congenital heart defects.  PLOS Biology, 14, e2000197. doi: 10.1371/journal.pbio.2000197.  PMID: 27606604.

Hsia, K., M.-J. Yang, W.-M. Chen, C.-L. Yao, C.-H. Lin, C.-C. Loong, Y.-L. Huang, Y.-T. Lin, A.D. Lander, H. Lee and J.H. Lu (2017). Sphingosine-1-Phosphate Improves Endothelialization with Reduction of Thrombosis in Recellularized Human Umbilical Vein Graft by Inhibiting Syndecan-1 Shedding. Acta Biomaterialia, Mar 15;51:341-350. doi: 10.1016/j.actbio.2017.01.050. Epub 2017 Jan 18. PubMed PMID: 28110073

Wortman J.C., M. Nahmad, P.C. Zhang, A.D. Lander and C.C. Yu (2017) Expanding signaling-molecule wavefront model of uniform growth and cell polarization in the Drosophila wing primordium. PLoS Computational Biol, 13, e1005610. doi: 10.1371/journal.pcbi.1005610. PMID: 28671940.

Newkirk, D.A., Y.-Y. Chen, R. Chien, W. Zeng, J. Biesinger, E. Flowers, S. Kawauchi, R. Santos, A.L. Calof, A.D. Lander, X. Xie, K. Yokomori (2017) The effect of Nipped-B-like (Nipbl) haploinsufficiency on genome-wide cohesin binding and target gene expression: modeling Cornelia de Lange Syndrome. Clin Epigenetics 9, 89. doi: 10.1186/s13148-017-0391-x. eCollection 2017. PMID: 28855971; PMCID: PMC5574093.

Calof, A.L., R. Santos, L. Groves, C. Oliver, and A.D. Lander (2020) Cornelia de Lange Syndrome: Insights into Neural Development from Clinical Studies and Animal Models.  In:  Comprehensive Developmental Neurosciences Series, 2nd Edition, Neural Developmental Disorders Section (Anthony Winshaw-Boris, Section Editor; John Rubenstein and Pasko Rakic, Senior Editors-in-Chief), Academic Press. 426 pages. ISBN 9780128144107. doi: 10.1016/B978-0-12-814409-1.00006-9; pp.129-156.

Lander A.D., Q. Nie, C. Sanchez-Tapia, A. Simonyan and F.Y.M. Wan (2020) Regulatory Feedback on Receptor and Non-receptor Synthesis for Robust Signaling.  Developmental Dynamics, Mar;249(3):383-409. doi: 10.1002/dvdy.160. Epub 2020 Feb 24. PubMed PMID:32034817

Zhu Y, Y. Qiu, W. Chen, Q. Nie and A.D. Lander (2020) Scaling a Dpp morphogen gradient through feedback control of receptors and co-receptors.  Developmental Cell, 53, 724–739.  doi: 10.1016/j.devcel.2020.05.029

R. Ruiz-Vega, C.-F. Chen, E. Razzak, P. Vasudeva, T.B. Krasieva, J. Shiu, M.G. Caldwell, H. Yan, J. Lowengrub, A.K. Ganesan and A.D. Lander. (2020) Dynamics of nevus development implicate cell cooperation in the growth arrest of transformed melanocytes.  ELife, Oct 13;9:e61026. doi: 10.7554/eLife.61026. PMID: 33047672; PMCID: PMC7553774.

Lomeli L.M., A. Iniguez, P. Tata, N. Jena, Z.Y. Liu, R. Van Etten, A.D. Lander, B. Shahbaba, J.S. Lowengrub, V.N. Minin (2021) Optimal experimental design for mathematical models of haematopoiesis. J R Soc Interface. Jan;18(174):20200729. doi: 10.1098/rsif.2020.0729. Epub 2021 Jan 27. PMID: 33499768.

Kong, X., Y.Y. Chen, J. Lin, E. Flowers, E. Van Nostrand, S.M. Blue, J. Chau, C. I. Ma, I. Mohr, R. Thai, C. Yao, A. R. Ball, Jr., R. Chien, S. Kawauchi, R. Santos, A. L. Calof, A. D. Lander, Y, Shi, M. Okuwaki, G. W. Yeo, and K. Yokomori (202X).  The cohesin loader NIPBL interacts with pre-ribosomal RNA and treacle to regulate ribosomal RNA synthesis.  Submitted to ELife.

Sharrock, A.V., T.S. Mulligan, K.R. Hall, E.M. Williams, D.T. White, L. Zhang, F. Matthews, S. Nimmagadda, S. Washington, K. Le, D. Meir-Levi, O.L. Cox, M.T. Saxena, A.L. Calof, M.E. Lopez-Burks, A.D. Lander, D. Ding, H. Ji, D.F. Ackerley, J.S. Mumm (202X) NTR 2.0: a rationally engineered nitroreductase prodrug converting enzyme that substantially enhances targeted cell ablation efficacy.  bioRxiv 2020.05.22.111427;doi:; also submitted to Nature Methods.

Wang, M.X., Lander A.D. and Lai, P.Y. (202X) Regulatory Feedback Effects on Tissue Growth Dynamics in a Two-Stage Cell Lineage Model.  Submitted to J. Theoretical Biol.

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