Jarema Malicki, Ph.D.
Assistant Professor of Ophthalmology (Genetics)
jarema_malicki@meei.harvard.edu
Click here to link to: The Malicki Lab Page
Predocs: 1 Postdocs: 4 Completed PhD's: 0
Our research predominantly focuses on the genetic bases of cell polarity. To approach this fundamental biological problem in the nervous system, we isolated and described several classes of mutations using the zebrafish model. Cell polarity is a multifaceted problem that involves the subdivision of the cell membrane into biochemically distinct subdomains, intracellular transport, and cell-cell interactions. Our research focuses mainly on three aspects of cell polarity: apico-basal polarity of neuroepithelia, intraflagellar transport, and nuclear positioning. To approach the first of these problems, we are studying a group of loci that regulate the polarity of retinal neuroepithelium. Mutations in these genes result in a loss of apico-basal polarity in the neural tube and subsequently produce a massive disorganization of neurons, indicating that their function is essential for the formation of gross architectural features. The importance of cell polarity is also obvious in the differentiation of sensory neurons. We have shown, for example, that the differentiation and survival of photoreceptor cells, or auditory hair cells, depend on so-called intraflagellar transport (IFT) genes. These factors are thought to transport proteins in a polarized fashion along apical cilia of sensory neurons, and are essential for sensory cell function. The positioning of cell nuclei is yet another aspect of polarity. In many cells, including photoreceptors for example, cell nucleus is precisely positioned. We have found genetic defects in a motor mechanism essential for this process. The long-term goal of our studies is to provide a comprehensive picture of the multiple genetic mechanisms involved in the establishment and maintenance of correct polarity.
Selected Publications:
1. Settleman, J., Fazeli, A., Malicki, J., Horwitz, B. H. and DiMaio, D. (1989). Genetic evidence that acute morphologic transformation, induction of cellular DNA synthesis, and focus formation are mediated by a single activity of the bovine papillomavirus E5 protein. Mol Cell Biol 9, 5563-72.
2. Malicki, J., Schughart, K. and McGinnis, W. (1990). Mouse Hox-2.2 specifies thoracic segmental identity in Drosophila embryos and larvae. Cell 63, 961-967.
3. Malicki, J., Cianetti, L. C., Peschle, C. and McGinnis, W. (1992). A human HOX4B regulatory element provides head-specific expression in Drosophila embryos. Nature 358, 345-347.
4. Malicki, J., Bogarad, L. D., Martin, M. M., Ruddle, F. H. and McGinnis, W. (1993). Functional analysis of the mouse homeobox gene HoxB9 in Drosophila development. Mechanisms of Development 42, 139-150.
5. Abdelilah, S., Mountcastle-Shah, E., Harvey, M., Solnica-Krezel, L., Schier, A. F., Stemple, D. L., Malicki, J., Neuhauss, S. C., Zwartkruis, F., Stainier, D. Y. et al. (1996). Mutations affecting neural survival in the zebrafish Danio rerio. Development 123, 217-227.
6. Driever, W., Solnica-Krezel, L., Schier, A. F., Neuhauss, S. C., Malicki, J., Stemple, D. L., Stainier, D. Y., Zwartkruis, F., Abdelilah, S., Rangini, Z. et al. (1996). A genetic screen for mutations affecting embryogenesis in zebrafish. Development 123, 37-46.
7. Malicki, J., Neuhauss, S. C., Schier, A. F., Solnica-Krezel, L., Stemple, D. L., Stainier, D. Y., Abdelilah, S., Zwartkruis, F., Rangini, Z. and Driever, W. (1996a). Mutations affecting development of the zebrafish retina. Development 123, 263-273.
8. Malicki, J., Schier, A. F., Solnica-Krezel, L., Stemple, D. L., Neuhauss, S. C., Stainier, D. Y., Abdelilah, S., Rangini, Z., Zwartkruis, F. and Driever, W. (1996b). Mutations affecting development of the zebrafish ear. Development 123, 275-283.
9. Neuhauss, S. C., Solnica-Krezel, L., Schier, A. F., Zwartkruis, F., Stemple, D. L., Malicki, J., Abdelilah, S., Stainier, D. Y. and Driever, W. (1996). Mutations affecting craniofacial development in zebrafish. Development 123, 357-67.
10. Pack, M., Solnica-Krezel, L., Malicki, J., Neuhauss, S. C., Schier, A. F., Stemple, D. L., Driever, W. and Fishman, M. C. (1996). Mutations affecting development of zebrafish digestive organs. Development 123, 321-8.
11. Schier, A. F., Neuhauss, S. C., Harvey, M., Malicki, J., Solnica-Krezel, L., Stainier, D. Y., Zwartkruis, F., Abdelilah, S., Stemple, D. L., Rangini, Z. et al. (1996). Mutations affecting the development of the embryonic zebrafish brain. Development 123, 165-178.
12. Solnica-Krezel, L., Stemple, D. L., Mountcastle-Shah, E., Rangini, Z., Neuhauss, S. C., Malicki, J., Schier, A. F., Stainier, D. Y., Zwartkruis, F., Abdelilah, S. et al. (1996). Mutations affecting cell fates and cellular rearrangements during gastrulation in zebrafish. Development 123, 67-80.
13. Stainier, D. Y., Fouquet, B., Chen, J. N., Warren, K. S., Weinstein, B. M., Meiler, S. E., Mohideen, M. A., Neuhauss, S. C., Solnica-Krezel, L., Schier, A. F. et al. (1996). Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo. Development 123, 285-92.
14. Stemple, D. L., Solnica-Krezel, L., Zwartkruis, F., Neuhauss, S. C., Schier, A. F., Malicki, J., Stainier, D. Y., Abdelilah, S., Rangini, Z., Mountcastle-Shah, E. et al. (1996). Mutations affecting development of the notochord in zebrafish. Development 123, 117-28.
15. Weinstein, B. M., Schier, A. F., Abdelilah, S., Malicki, J., Solnica-Krezel, L., Stemple, D. L., Stainier, D. Y., Zwartkruis, F., Driever, W. and Fishman, M. C. (1996). Hematopoietic mutations in the zebrafish. Development 123, 303-9.
16. Driever, W., Schier, A., Malicki, J. and Stemple, D. (1997). Genetic analysis of pattern formation in the zebrafish nervous system. In From Membrane to Mind, (ed. N. Elsner and H. Wässle), pp. 119-137. Stuttgart: Georg Thieme Verlag.
17. Marlow, F., Zwartkruis, F., Malicki, J., Neuhauss, S. C., Abbas, L., Weaver, M., Driever, W. and Solnica-Krezel, L. (1998). Functional interactions of genes mediating convergent extension, knypek and trilobite, during the partitioning of the eye primordium in zebrafish. Developmental Biology 203, 382-99.
18. Malicki, J. and Driever, W. (1999). oko meduzy mutations affect neuronal patterning in the zebrafish retina and reveal cell-cell interactions of the retinal neuroepithelial sheet. Development 126, 1235-1246.
19. Malicki, J. (1999). Development of the retina. Methods Cell Biol. 59, 273-299.
20. Link, B. A., Fadool, J. M., Malicki, J. and Dowling, J. E. (2000). The zebrafish young mutation acts non-cell-autonomously to uncouple differentiation from specification for all retinal cells. Development 127, 2177-2188.
21. Malicki, J. (2000a). Genetic analysis of eye development in zebrafish. Results and Problems in Cell Differentiation 31, 257-282.
22. Malicki, J. (2000b). Harnessing the power of forward genetics - analysis of neuronal diversity and patterning in the zebrafish retina. Trends Neurosci 23, 531-541.
23. Bang, P. I., Sewell, W. F. and Malicki, J. J. (2001). Morphology and cell type heterogeneities of the inner ear epithelia in adult and juvenile zebrafish (Danio rerio). Journal of Comparative Neurology 438, 173-90.
24. Doerre, G. and Malicki, J. (2001). A Mutation of Early Photoreceptor Development, mikre oko, Reveals Cell- Cell Interactions Involved in the Survival and Differentiation of Zebrafish Photoreceptors. Journal of Neuroscience 21, 6745-57.
25. Pujic, Z. and Malicki, J. (2001). Mutation of the zebrafish glass onion locus causes early cell-nonautonomous loss of neuroepithelial integrity followed by severe neuronal patterning defects in the retina. Developmental Biology 234, 454-69.
26. Bang, P., Yelick, P., Malicki, J. and Sewell, W. (2002). High-throughput behavioral screening method for detecting auditory response defects in zebrafish. J Neurosci Methods 118, 177.
27. Doerre, G. and Malicki, J. (2002). Genetic analysis of photoreceptor cell development in the zebrafish retina. Mechanisms of Development 110, 125-138.
28. Wei, X. and Malicki, J. (2002). nagie oko, encoding a MAGUK-family protein, is essential for cellular patterning of the retina. Nature Genetics 31, 150-157.
29. Easter, S. S., Jr. and Malicki, J. J. (2002). The zebrafish eye: developmental and genetic analysis. In Results Probl Cell Differ, vol. 40, pp. 346-70.
30. Malicki, J., Jo, H., Wei, X., Hsiung, M. and Pujic, Z. (2002a). Analysis of gene function in the zebrafish retina. Methods 28, 427-38.
31. Malicki, J. J., Pujic, Z., Thisse, C., Thisse, B. and Wei, X. (2002b). Forward and reverse genetic approaches to the analysis of eye development in zebrafish. Vision Research 42, 527-33.
32. Malicki, J., Jo, H. and Pujic, Z. (2003). Zebrafish N-cadherin, encoded by the glass onion locus, plays an essential role in retinal patterning. Developmental Biology 259, 95-108.
33. Tsujikawa, M. and Malicki, J. (2004a). Intraflagellar transport genes are essential for differentiation and survival of vertebrate sensory neurons. Neuron 42, 703-16.
34. Tsujikawa, M. and Malicki, J. (2004b). Genetics of photoreceptor development and function in zebrafish. Int J Dev Biol 48, 925-34.
35. Avanesov, A. and Malicki, J. (2004). Approaches to study neurogenesis in the zebrafish retina. Methods Cell Biol 76, 333-84.
36. Malicki, J. (2004). Cell fate decisions and patterning in the vertebrate retina: the importance of timing, asymmetry, polarity and waves. Curr Opin Neurobiol 14, 15-21.
37. Pujic, Z. and Malicki, J. (2004). Retinal pattern and the genetic basis of its formation in zebrafish. Semin Cell Dev Biol 15, 105-14.
38. Avanesov, A., Dahm, R., Sewell, W. F. and Malicki, J. J. (2005). Mutations that affect the survival of selected amacrine cell subpopulations define a new class of genetic defects in the vertebrate retina. Dev Biol 285, 138-55.
39. Otteson, D. C., Tsujikawa, M., Gunatilaka, T., Malicki, J. and Zack, D. J. (2005). Genomic organization of zebrafish cone-rod homeobox gene and exclusion as a candidate gene for retinal degeneration in niezerka and mikre oko. Mol Vis 11, 986-95.
40. Omori, Y. and Malicki, J. (2006). oko meduzy and Related crumbs Genes Are Determinants of Apical Cell Features in the Vertebrate Embryo. Current Biology 16, 945-57.
41. Pujic, Z., Omori, Y., Tsujikawa, M., Thisse, B., Thisse, C. and Malicki, J. (2006). Reverse genetic analysis of neurogenesis in the zebrafish retina. Dev Biol 293, 330-47.
42. Zhao, X. C., Yee, R. W., Norcom, E., Burgess, H., Avanesov, A. S., Barrish, J. P. and Malicki, J. (2006). The zebrafish cornea: structure and development. Invest Ophthalmol Vis Sci 47, 4341-8.
43. Li, G., Liu, T., Nie, J., Guo, L., Malicki, J., Mara, A., Holley, S. A., Xia, W. and Wong, S. T. (2007). Detection of blob objects in microscopic zebrafish images based on gradient vector diffusion. Cytometry A 71, 835-45.
44. Schibler, A. and Malicki, J. (2007). A screen for genetic defects of the zebrafish ear. Mech Dev 124, 592-604.
45. Tsujikawa, M., Omori, Y., Biyanwila, J. and Malicki, J. (2007). Mechanism of positioning the cell nucleus in vertebrate photoreceptors. Proc Natl Acad Sci U S A 104, 14819-24.
46. Zhao, C. and Malicki, J. (2007). Genetic defects of pronephric cilia in zebrafish. Mech Dev 124, 605-16.
47. Blachon, S., Gopalakrishnan, J., Omori, Y., Polyanovsky, A., Church, A., Nicastro, D., Malicki, J. and Avidor-Reiss, T. (2008). Drosophila asterless and Vertebrate Cep152 Are Orthologs Essential for Centriole Duplication. Genetics 180, 2081-94.
48. Kitambi, S. S. and Malicki, J. J. (2008). Spatiotemporal features of neurogenesis in the retina of medaka, Oryzias latipes. Dev Dyn 237, 3870-81.
49. Liu, T., Li, G., Nie, J., Tarokh, A., Zhou, X., Guo, L., Malicki, J., Xia, W. and Wong, S. T. (2008). An automated method for cell detection in zebrafish. Neuroinformatics 6, 5-21.
50. Omori, Y., Zhao, C., Saras, A., Mukhopadhyay, S., Kim, W., Furukawa, T., Sengupta, P., Veraksa, A. and Malicki, J. (2008). Elipsa is an early determinant of ciliogenesis that links the IFT particle to membrane-associated small GTPase Rab8. Nature Cell Bio 10, 437-444.
51. Kitambi, S. S., McCulloch, K. J., Peterson, R. T. and Malicki, J. J. (2009). Small molecule screen for compounds that affect vascular development in the zebrafish retina. Mech Dev 126, 464-77.
52. McMahon, T. T., Kim, L. S., Fishman, G. A., Stone, E. M., Zhao, X. C., Yee, R. W. and Malicki, J. (2009). CRB1 gene mutations are associated with keratoconus in patients with leber congenital amaurosis. Invest Ophthalmol Vis Sci 50, 3185-7.
53. Zhang, Y., McCulloch, K. and Malicki, J. (2009). Lens transplantation in zebrafish and its application in the analysis of eye mutants. J Vis Exp.
54. Jing, X. and Malicki, J. (2009). Zebrafish ale oko, an essential determinant of sensory neuron survival and the polarity of retinal radial glia, encodes the p50 subunit of dynactin. Deveopment, in press.
55. Malicki, J. and Avanesov, A. (2009). Approaches to study the zebrafish retina. Essentials, in press.
56. Malicki, J. and Kennedy, B. N. (2009). What drives cell morphogenesis - a look inside the vertebrate photoreceptor. Dev Dyn, in press.
