Hamed Jafar-Nejad

Cell biological regulation of developmental signaling pathways

Despite the diversity of cellular form and function in animals, a handful of signaling pathways are involved in a large number of decisions made by animal cells during development and afterwards. For example, the Notch signaling pathway regulates processes as diverse as cell fate specification, stem cell proliferation and maintenance, apoptosis, compartment boundary formation and neurite outgrowth. The focus of my lab is to understand how animals fine-tune such ubiquitous pathways to achieve and maintain cellular diversity. We performed a forward genetic screen in Drosophila to isolate novel regulators of the Notch pathway. Interestingly, most novel genes discovered in this screen are involved in posttranslational modification and/or intracellular trafficking of the Notch pathway components. Currently, my lab focuses on the characterization of one of these genes, rumi, which encodes an endoplasmic reticulum protein with homology to bacterial and fungal sugar modifiers. Rumi is a general regulator of Notch signaling, and loss-of-function alleles of rumi exhibit a temperature-sensitive and reversible loss of Notch signaling. A combination of genetic, cell biological and biochemical approaches is being used to elucidate the mechanism of Rumi function. Moreover, we are using the sensitive phenotype of rumi as the basis for a modifier screen to identify other Notch “fine-tuning” genes. Rumi is a highly conserved protein, and vertebrate studies have shown that manipulation of the Notch pathway might be of potential therapeutic value in several disease contexts, including inner ear hair cell loss, muscle injury and demyelination. Therefore, we hope that by shedding light on the interface of cell biology and development, our research will not only unravel some of the strategies used by animals to regulate signaling, but might also contribute to efforts aimed at altering the outcome of human diseases.

Selected Publications

Jafar-Nejad H, Norga K, Bellen HJ (2002) Numb: "Adapting" notch for endocytosis. Developmental Cell 3:155-156.

Zhai RG, Hiesinger PR, Koh TW, Verstreken P, Schulze KL, Cao Y, Jafar-Nejad H, Norga KK, Pan H, Bayat V, Greenbaum MP, Bellen HJ (2003) Mapping Drosophila mutations with molecularly defined P element insertions. Proceedings of the National Academy of Sciences U.S.A. 100:10860-10865.

Jafar-Nejad H*, Acar M*, Nolo R, Lacin H, Pan H, Parkhurst SM, Bellen HJ (2003) Senseless acts as a binary switch during sensory organ precursor selection. Genes and Development 17:2966-2978. (*equal contribution)

Quan XJ, Denayer T, Yan J, Jafar-Nejad H, Philippi A, Lichtarge O, Vleminckx K, Hassan BA (2004) Evolution of neural precursor selection: functional divergence of proneural proteins. Development 131:1679-1689.

Jafar-Nejad H, Bellen HJ (2004) Gfi/Pag-3/senseless zinc finger proteins: a unifying theme? Molecular and Cellular Biology 24:8803-8812.

Tsuda H, Jafar-Nejad H, Patel AJ, Sun Y, Chen HK, Rose MF, Venken KJ, Botas J, Orr HT, Bellen HJ, Zoghbi HY (2005) The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins. Cell 122:633-644.

Jafar-Nejad H, Andrews HK, Acar M, Bayat V, Wirtz-Peitz F, Mehta SQ, Knoblich JA, Bellen HJ (2005) Sec15, a component of the exocyst, promotes Notch signaling during the asymmetric division of Drosophila sensory organ precursors. Developmental Cell 9:351-363.

Hamaratoglu F, Willecke M, Kango-Singh M, Nolo R, Hyun E, Tao C, Jafar-Nejad H, Halder G (2006) The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nature Cell Biology 8:27-36.

Jafar-Nejad H, Tien AC, Acar M, Bellen HJ (2006) Senseless and Daughterless confer neuronal identity to epithelial cells in the Drosophila wing margin. Development 133:1683-1692.

Acar M*, Jafar-Nejad H*, Giagtzoglou N, Yallampalli S, David G, He Y, Delidakis C, Bellen HJ (2006) Senseless physically interacts with proneural proteins and functions as a transcriptional co-activator. Development 133:1979-1989. (*equal contribution)

Contact Information

Hamed Jafar-Nejad, M.D.

Institute of Molecular Medicine

University of Texas Health Science Center at Houston

1825 Pressler St., SRB-430C

Houston, Texas 77030, U.S.A.

Tel: (713) 500-3483

Fax: (713) 500-2420

E-mail: Hamed.Jafar-Nejad@uth.tmc.edu