Calof, Anne - University of California, Irvine - Department of Developmental and Cell Biology

研究领域

Systems Biology of Stem Cells and Human Developmental Disorders–The Calof lab uses genetics, molecular biology and systems biology approaches to address questions in development, regeneration, and tissue homeostasis. We also work on vertebrate animal model systems to try to understand the etiology of certain human genetic diseases that affect development and function, especially of the nervous system. Among the questions we are addressing are: How can we use molecular, cellular, and computational approaches together to gain insights into the behaviors of endogenous stem cells during development and regeneration of epithelia, particularly neural (sensory) epithelia? In particular, we are interested in understanding how interacting feedback loops mediated by different molecular signals interact to achieve the performance objectives of developing and regenerating epithelia. We move between wet-lab experimental approaches, to modeling and back again to experimental approaches, to test these ideas. Calof Lab WebsiteCan mouse and zebrafish models of Cornelia de Lange Syndrome provide insights into the many structural and physiological disorders, also common in non-syndromic birth defects, which are associated with this human genetic disease? Of particular interest are heart defects, limb reduction defects, and neural pathologies. Are the developmental phenotypes observed in birth defects disorders (e.g. heart defects, autism) the result of the combinatorial actions of small changes in activities of many genes, rather than major changes in the activity of any one single gene? We use conditional/invertible alleles (FLEX alleles) of genes, in combination with unbiased transcriptome screens, to help us understand how small changes in gene expression that take place in particular locations and/or at particular developmental epochs, lead to widespread structural birth defects.

近期论文

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Kawauchi, S., Kim, J., Santos, R., Wu, H. H., Lander, A. D. and Calof, A. L. (2009). Foxg1 promotes olfactory neurogenesis by antagonizing Gdf11. Development 136, 1453-64. Beites, CL, Hollenbeck, PLW, Kim, J, Lovell-Badge, R, Lander, AD, and Calof, AL (2009) Follistatin modulates a BMP autoregulatory loop to control size and patterning of sensory domains in the developing tongue. Development, 136: 2187-2197. Kawauchi, S*, Calof, AL*, Santos, R., Lopez-Burks, ME, Young, CM, Hoang, MP, Chua, A., Lao, T., Lechner, MS, Daniel, JA, Nussenzweig, A., Kitzes, L., Yokomori, K., Hallgrimsson, B. and Lander, A.D. (2009) Multiple organ system defects and transcriptional dysregulation in a mouse model of Cornelia de Lange Syndrome. PLoS Genetics 5(9): e1000650. Doi:10.1371/journal.pgen.1000650. (* = Co-first authors) Gokoffski, K.K., Kawauchi, S., H.-H. Wu, R. Santos, P.W.L. Hollenbeck, A.D. Lander and A.L. Calof (2010) “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, pp. 241-265. PMID:21882434 Chou, C.-S., Lo, W.-C., Gokoffski, K.K., Zhang, Y.-T., Wan, F.Y.M., Lander, A.D., Calof, A.L., and NI, Q. (2010) Spatial dynamics of multistage cell lineages in tissue stratification. Biophys. J. 99 (10): 3145-3154. Chien R, Zeng W, Kawauchi S, Santos R, Gregson HC, Schmiesing JA, Newkirk D, Kong X, Ball AR J, Calof AL, Lander AD, Groudine M & Yokomori K (2011) Cohesin mediates chromatin interactions that regulate mammalian b-globin expression. J. Biol. Chem. 286: DOI 10.1074 Gokoffski K, Wu H-H, Beites CL, Kim J, Kim E, Matzuk MM, Johnson JE, Lander AD & Calof AL (2011) Activin and GDF11 collaborate in feedback control of neuroepithelial stem cell proliferation and fate. Development, 138: pp. 4131-4142. Muto A, Calof AL, Lander AD, and Schilling, T.F. (2011) Multifactoral origins of heart and gut defects in nipbl-deficient zebrafish, a model of Cornelia de Lange Syndrome. PLoS Biology Oct;9(10):e1001181. Epub 2011 Oct 25. (comment: PLoS Biol. 2011 Oct;9(10):e1001180) PMCID: PMC3201921 Santos R, Wu H-H, Hamilton J, Pinter R, Hindges R & Calof, AL (2012) Restoration of retinal development in Vsx2 deficient mice by reduction of Gdf11 activity. Adv. Exp. Med. Biol. 723: 671-677. PMID 22183392