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Jarema Malicki, Ph.D.

Assistant Professor of Ophthalmology (Genetics)

Massachusetts Eye and Ear Infirmary
R513
243 Charles St
Boston, MA 02114
Telephone: 617-573-4372
Fax: 617- 573-4290
E-mail: jarema_malicki@meei.harvard.edu
Webpage: The Malicki Lab Page
Predocs: 1 Postdocs: 4 Completed PhD's: 0

Jarema Malicki

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.

References:

  • 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.
  • 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.
  • Tsujikawa, M. and Malicki, J. (2004). Intraflagellar transport genes are essential for differentiation and survival of vertebrate sensory neurons. Neuron 42. 703-16.
  • 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.
  • Tsujikawa, M., Omori, Y., Biyanwila, J. & Malicki, J. Mechanism of positioning the cell nucleus in vertebrate photoreceptors. Proc Natl Acad Sci U S A 104, 14819-24 (2007).