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Hugo Bellen Baylor College of Medicine Department: Departments of Molecular & Human Genetics, Molecular & Cellular Biology, Neuroscience, and the Developmental Biology Graduate Program Address: One Baylor Plaza, T628, MS: BCM235 Houston, TX 77030 Phone: (713) 798-5272 Fax: (713) 798-3694 Email: hbellen@bcm.edu Web: www.bcm.edu/genetics/faculty/index.html

Education

Commercial Engineer (Engineering & M.B.A.), Magna Cum Laude; Preveterinary Medicine, Magna Cum Laude
Doctor in Veterinary Medicine, Magna Cum Laude; Ph.D. in Genetics, University of California, Davis, CA
Postdoctoral Researcher, supported by a N.A.T.O. Fellowship

Honors

Upjohn Award, Best Thesis in Veterinary Medicine, Belgium, July 1983
Fullbright Award, Belgian-American Educational Foundation, July 1983
Distinguished Scholarship, University of California, Davis, September 1985
N.A.T.O. Fellowship, July 1986 and July 1987
Michael E. DeBakey, M.D., Excellence in Research Award, October 1995
The Dean's Faculty Award for Excellence in Graduate Education, March 1999
Charles Darwin Chair in Genetics, October 1999
The March of Dimes Chair in Developmental Biology, May 2000

Research Topic

Genetic and molecular analysis of neurotransmitter release and nervous system development in Drosophila

Research Description

Communication within the nervous system involves neurotransmitter release from synaptic vesicles that fuse with the presynaptic membrane following a calcium influx during an action potential. The biochemical and molecular events underlying neurotransmitter release and the trafficking of synaptic vesicles within the presynaptic terminal are currently being intensely investigated. We and others have shown that proteins implicated in neurotransmitter release in vertebrates have been extremely well conserved during evolution. Hence, it has been relatively straightforward to isolate the Drosophila homologues of vertebrate proteins implicated in synaptic vesicle trafficking and to create mutations in the corresponding genes using a reverse genetic approach. The fruitfly, Drosophila, is an excellent model system to study this question because the awesome power of genetics combined with the availability of several functional assays, including sophisticated electrophysiological and electron microscopy paradigms, allow us to describe the defects associated with these mutations. These studies combined with FM1-43 dye-uptake experiments allow us to determine when and where these proteins are precisely required in the synaptic vesicle cycle. Our laboratory presently focuses on VAP33, Hrs, Endophilin, DAP160, and several novel proteins identified in forward genetic screens.

To gain a more fundamental insight into the molecular mechanisms of the development of the nervous system and the process underlying neurotransmitter release, we have performed chemical and P-element mutagenesis screens to identify mutations that affect the development of the peripheral nervous system. More than 30 novel genes have presently been isolated. We are presently focusing on the gene, senseless. The senseless gene is required for proper development of most cell types of the embryonic and adult peripheral nervous system (PNS) of Drosophila. Senseless is a nuclear protein with four Zn-fingers that is expressed and required in the sensory organ precursors (SOP) for proper proneural gene expression. Ectopic expression of Senseless in many ectodermal cells causes induction of PNS external sensory organ formation and is able to recreate an ectopic proneural field. Hence, senseless is both necessary and sufficient for PNS development. Our data indicate that proneural genes activate senseless expression. Senseless is then in turn required to further activate and maintain proneural gene expression. This feedback mechanism is essential for selective enhancement and maintenance of proneural gene expression in the SOPs.

Selected Publications

• Hiesinger PR, Fayyazuddin A, Mehta SQ, Rosenmund T, Schulze KL, Zhai RG, Verstreken P, Cao J, Zhou Y, Kunz J, Bellen HJ (2005). The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila. Cell 121: 607-620.
• Verstreken P, Ly CV, Venken KJ, Koh T-W, Zhou Y, Bellen HJ (2005). Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron 47: 365-378.
• Venken KJT, He Y, Hoskins RA, Bellen HJ (2006). P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science 314: 1747-1751.
• Acar M, Jafar-Nejad H, Takeuchi H, Rajan A, Ibrani D, Rana NA, Pan H, Haltiwanger RS, Bellen HJ (2008). Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell 132: 247-258.
• Zhai RG, Zhang F, Hiesinger PR, Cao Y, Haueter CM, Bellen HJ (2008). NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration. Nature 452: 887-891.
• Tsuda H, Han SM, Yang Y, Tong C, Lin YQ, Mohan K, Haueter C, Zoghbi A, Harati Y, Kwan J, Miller MA, Bellen HJ (2008). The Amyotrophic Lateral Sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. Cell 133: 963-977
• Venken KJ, Carlson JW, Schulze KL, Pan H, He Y, Spokony R, Wan KH, Koriabine M, de Jong PJ, White KP, Bellen HJ, Hoskins RA (2009). Versatile P[acman] BAC libraries for transgenesis studies in Drosophila melanogaster. Nature Methods 6: 431-434.
• Rajan A, Tien A-C, Haueter CM, Schulze KL, Bellen HJ (2009). The Arp2/3 complex and WASp are required for apical trafficking of Delta into microvilli during cell fate specification of sensory organ precursors. Nature Cell Biology 11: 815-824.
• Fotowat H, Fayyazuddin A, Bellen HJ, Gabbiani F (2009). A novel neuronal pathway for visually guided escape in Drosophila melanogaster. Journal of Neurophysiology 102: 875-885.
• Verstreken P, Ohyama T, Haueter C, Habets RL, Lin YQ, Swan LE, Ly CV, Venken KJ, De Camilli P, Bellen HJ (2009). Tweek, an evolutionarily conserved protein, is required for synaptic vesicle recycling. Neuron 63: 203-215.
• Yao CK, Lin YQ, Ly CV, Ohyama T, Haueter C, Moiseenkova-Bell VY, Wensel TG Bellen HJ (2009). A synaptic vesicle- and presynaptic membrane-associated ion channel regulates resting Ca2+ levels and synaptic endocytosis. Cell, in press.

Lab Members

Current Graduate Students
Former Grad Students
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Lab Photos

Last edited on: August 23, 2009