Hamed Jafar-Nejad, M.D.
Assistant Professor
Center for Neurodegenerative Diseases
phone 713.500.3483;
fax 713.500.2420
Hamed.Jafar-Nejad@uth.tmc.edu
Cell Biological Regulation of Signaling Pathways
Hamed Jafar-Nejad received his M.D. from Tehran University of Medical Sciences in 1994. To prepare himself for a science career, he worked as a research assistant in Iran to learn basic molecular biology techniques. In 1999, he moved to Canada to pursue his training in the laboratory of Dr. Paul Albert at the Neuroscience Research Institute, University of Ottawa, where he studied the transcriptional regulation of the serotonin 1A receptor in rat neuronal cell lines.
Late in 2000, he started his postdoctoral studies on Drosophila nervous system development in the laboratory of Dr. Hugo Bellen at the Howard Hughes Medical Institute, Baylor College of Medicine, Houston. In December 2006, he joined the Institute of Molecular Medicine as an Assistant Professor. He is also a member of the Graduate School of Biomedical Sciences at UT and the Program in Developmental Biology at Baylor College of Medicine.
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, asymmetric division, stem cell proliferation and maintenance, apoptosis, and compartment boundary formation. The focus of the Jafar-Nejad lab is to understand how animals fine-tune such ubiquitous pathways to achieve and maintain cellular diversity. During his postdoctoral studies, Hamed and his colleagues 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, the 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, the sensitive phenotype of rumi is being used 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 can be of potential therapeutic value in several disease contexts, including inner ear hair cell loss, muscle injury and demyelination.
Therefore, the hope is that by shedding light on the interface of cell biology and development, this line of 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.
Recent Publications
Acar M*, Jafar-Nejad H*, Takeuchi H*, Rajan A, Ibrani D, Rana D, Pan H, Haltiwanger RS and Bellen HJ.
(2008) Rumi is a CAP10 domain glycosyltransferase that modifies notch and is required for notch signaling. Cell 132(2): 247-258. (* equal contribution)
Rogaeva A, Ou XM, Jafar-Nejad H, Lemonde S and Albert PR. (2007) Differential repression by Freud-1/CC2D1A at a polymorphic site in the dopamine-D2 receptor gene. Journal of Biological Chemistry 282(29): 20897-20905.
Acar M*, Jafar-Nejad H*, Giagtzoglou N, Yallampalli S, David G, He Y, Delidakis C and Bellen HJ. (2006) Senseless physically interacts with proneural proteins and functions as a transcriptional co-activator. Development 133(10): 1979-1989. (* equal contribution)
Jafar-Nejad H, Tien A, Acar M and Bellen HJ. (2006) Senseless and Daughterless confer neuronal identity to epithelial cells in the Drosophila wing margin. Development 133(9): 1683-1692.
Hamaratoglu F, Willecke M, Kango-Singh M, Nolo R, Hyun E, Tao C, Jafar-Nejad H and Halder G. (2006) The tumor suppressor genes NF2/Merlin and Expanded act through Hippo signaling to regulate cell proliferation and apoptosis. Nature Cell Biology 8(1): 27-36.
Jafar-Nejad H, Andrews HK, Acar M, Bayat V, Wirtz-Peitz F, Mehta SQ, Knoblich JA and Bellen HJ. (2005) Sec15, a member of the exocyst, promotes Notch signaling during the asymmetric division of Drosophila sensory organ precursors. Developmental Cell 9(3): 351-363.
Tsuda H, Jafar-Nejad H, Patel AJ, Sun Y, Chen H, Rose MF, Venken KJT, Botas J, Orr HT, Bellen HJ and Zoghbi HY. (2005) The AXH domain in Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins. Cell 122(4): 633-44.
Jafar-Nejad H and Bellen HJ. (2004) The Gfi/Pag-3/Senseless zinc finger proteins: a unifying theme? Molecular and Cellular Biology 24(20):8803-12.
Quan XJ, Denayer T, Yan J, Jafar-Nejad H, Philippi A, Lichtarge O, Vleminckx C and Hassan BA. (2004) Evolution of neural precursor selection: functional divergence of proneural proteins. Development 131(8):1679-89.
Jafar-Nejad H*, Acar M*, Nolo R, Lacin H, Pan H, Parkhurst SM and Bellen HJ. (2003) Senseless acts as a binary switch during sensory organ precursor selection. Genes & Development 17(23): 2966-78. (* equal contribution)
Zhai RG, Hiesinger PR, Koh TW, Verstreken P, Schulze KL, Cao Y, Jafar-Nejad H, Norga KK, Pan H, Bayat V, Greenbaum MP and Bellen HJ. (2003) Mapping Drosophila mutations with molecularly defined P element insertions. Proceedings of the National Academy of Sciences 100(19): 10860-5.
Ou XM, Lemonde S, Jafar-Nejad H, Bown CD, Goto A, Rogaeva A and Albert PR. (2003) Freud-1: A neuronal calcium-regulated repressor of the 5-HT1A receptor gene. Journal of Neuroscience 23(19): 7415-25.