Hugo J. Bellen

Hugo J. Bellen is a professor at Baylor College of Medicine and an investigator at the Howard Hughes Medical Institute[8] who studies genetics and neurobiology in the model organism, Drosophila melanogaster, the fruit fly.

Hugo J. Bellen
Born1953 (age 67–68)
NationalityBelgium
CitizenshipUSA
Alma mater
Awards
  • Fulbright Award (1983)
  • N.A.T.O. Fellowship (1986-1987)
  • Michael E. DeBakey, M.D., Excellence in Research Award (1995, 2016)[1]
  • The Dean's Faculty Award for Excellence in Graduate Education (1999)
  • Charles Darwin Chair in Genetics (1999)
  • The March of Dimes Chair in Developmental Biology (2000)
  • Distinguished Service Professor of BCM (2010)
  • Distinguished Alumnus Award, University of California, Davis (2011)[2]
  • The Linda and Jack Gill Distinguished Neuroscience Investigator Award (2012)[3]
  • George W. Beadle Award (2014)[4]
  • Miegunyah Distinguished Fellowship of the University of Melbourne (2015)[5]
  • Member of the United States National Academy of Sciences (2020)[6]
  • Member of the American Academy of Arts and Sciences (2020)[7]
Scientific career
FieldsGenetics, Developmental Biology, Neuroscience
InstitutionsBaylor College of Medicine, Howard Hughes Medical Institute
Doctoral advisorJohn A. Kiger Jr.
Other academic advisorsWalter J. Gehring, postdoctoral advisor

Education and Career

Hugo Bellen is an Investigator of the Howard Hughes Medical Institute and Distinguished Service Professor at Baylor College of Medicine (BCM) in the Departments of Molecular and Human Genetics and Neuroscience. Originally from Belgium, Dr. Bellen earned a degree in Business Engineering from the Solvay School of Business at the University of Brussels, a Pre-Veterinary Medicine degree from the University of Antwerp and a doctoral degree in Veterinary Medicine from the University of Ghent. He received his Ph.D. in Genetics from the University of California at Davis and completed postdoctoral research in the laboratory of Dr. Walter Gehring at the University of Basel in Switzerland. He started his independent career as an HHMI Investigator at BCM in 1989 and joined the Neurological Research Institute at Texas Children's Hospital at its inception in 2011.

One of the world's premier researchers in Drosophila (fruit fly) genetics, Dr. Bellen's group has made major contributions to our understanding of nervous system development, synaptic transmission and mechanisms of neurodegeneration. As the head of the Drosophila Gene Disruption Project, his laboratory has developed numerous sophisticated genetic tools and generated tens of thousands of reagents that have transformed Drosophila biology.

Dr. Bellen's current research focuses on the discovery of new human disease genes and elucidating pathogenic mechanisms of neurodevelopmental and neurodegenerative diseases using fruit flies in collaborations with human geneticists worldwide. His lab is the home of the Model Organisms Screening Center for the Undiagnosed Diseases Network of the National Institutes of Health.[9] In the past few years he has made major strides in solving key problems related to Friedreich's ataxia, Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease.[10]

Dr. Bellen has trained 38 graduate students, including 7 MSTP students, and 43 postdoctoral fellows who are successful in careers in academia and industry. Currently, 18 trainees are in the lab, including a mix of graduate students and postdoctoral fellows. Dr. Bellen received the BCM Presidential Award for Excellence in Leadership in Science and Research mentoring in 2018.

Dr. Bellen has organized numerous national and international meetings. He is currently co-organizer of TAGC 2020, The Allied Genetics Conference to be held in Washington, DC in 2020. He served as a member of the editorial board of the Journal of Cell Biology for 15 years, and is currently serving as a member of the editorial boards of eLife, PLoS Biology, and Genetics. He is the chair of the scientific advisory board of the Bloomington Drosophila Stock Center, and is a member of the scientific advisory boards of FlyBase, the NHGRI Alliance of Genome Resources, the Gill Center for Biomolecular Science, and the INADcure Foundation. He was previously on the scientific advisory boards of the Max Planck Institute in Göttingen, Germany, the Academia Sinica in Taipei, Taiwan, the KAIST in Daejeon, Korea, and the VIB in Leuven, Belgium.

Dr. Bellen's awards include the George Beadle Award from the Genetics Society of America; the Linda & Jack Gill Distinguished Neuroscience Investigator Award from Indiana University; the Miegunyah Distinguished Visiting Fellowship from the University of Melbourne; the Distinguished Alumnus Award from the University of California, Davis; the Michael E. DeBakey, MD, Excellence in Research Award, and the Dean's Faculty Award for Excellence in Graduate Education from Baylor College of Medicine. Dr. Bellen served as the Director of the BCM Graduate Program in Developmental Biology for more than 20 years. He is also the March of Dimes Professor in Developmental Biology and the Charles Darwin Professor in Genetics at Baylor College of Medicine. On April 27, 2020 he was elected to the United States National Academy of Sciences in recognition of his achievements in research.

Research

Neurodegeneration

Dr. Bellen's current research focuses on an effort to decipher the mechanisms by which mutations in specific genes cause neurodegeneration, and to this end, he and his colleagues performed unbiased forward genetic screens in fruitflies that detect the progressive decline in function and morphology of photoreceptor neurons.[11] To date over 165 genes that cause a neurodegenerative phenotype when mutated have been uncovered by Dr. Bellen's group using this strategy.[12] Many of these genes encode homologues of human genes that are known to cause neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) (Lou Gehrig's disease),[13] Charcot-Marie-Tooth (CMT),[14] Parkinson's disease (PD),[15] Alzheimer's disease (AD), Leigh syndrome,[16] and others, and these studies will help provide a much better understanding of the molecular mechanisms by which neurodegeneration occurs. A prevailing theme among these mutants seems to be dysfunction of the neuronal mitochondria and an increasing inability to deal with oxidative stress, which manifests as lipid droplets.[17]

Technology

Bellen has pioneered the development of novel technologies that accelerate Drosophila research and are currently used by the majority of fly labs today. Bellen was a leader in the development of P element-mediated enhancer detection which allows for discovery and manipulation of genes and was the impetus for a collaborative and ongoing project to generate an insertion collection for the community. Furthermore, Bellen and colleagues devised a new transformation technology that permits site-specific integration of very large DNA fragments,[18] which led to the generation of a collection of flies carrying molecularly defined duplications for more than 90% of the Drosophila X-chromosome.[19] Hundreds of Drosophila researchers utilize this collection. Most recently his lab created a new transposable element (MiMIC)[20] that permits even more downstream manipulations via RMCE (recombinase-mediated cassette exchange), such as protein tagging and knockdown[21][22] and large scale homologous recombination. His research constantly evolves with the changing technology to meet the needs of the Drosophila community.

Neurotransmitter release

Bellen has made numerous important contributions in the field of synaptic transmission in Drosophila. Through unbiased forward genetic screens designed to detect perturbations in neuronal function, he has uncovered many genes involved in synaptic transmission and has used reverse genetics to help to establish their function. His lab was the first to provide in vivo evidence that Synaptotagmin 1 functions as the main Calcium sensor in synaptic transmission[23] and that Syntaxin-1A plays a critical role in synaptic vesicle (SV) fusion in vivo.[24] His lab showed that Endophilin[25] and Synaptojanin[26] control uncoating of SVs, that the V0 component of the v-ATPase affects SV fusion,[27] that synaptic mitochondria control SV dynamics,[28] and in addition discovered a novel calcium channel involved in SV biogenesis.[29] His pioneering work on synaptic vesicle trafficking molecules was later confirmed in the mouse.

Neuronal Development

Bellen and colleagues made important contributions to our understanding of Drosophila peripheral nervous system development and the fine-tuning of aspects of Notch signaling during this process. These discoveries were made by carrying out multiple forward genetic screens using the mutagen, ethyl methane sulfonate, as well as P elements. They discovered the protein Senseless[30] that is required for the development of the peripheral nervous system by boosting the action of proneural proteins and suppressing the action of Enhancer of split proteins.[31] They also discovered the protein Rumi[32] and determined it was required for O-glycosylation of Notch at many different sites and found that these sites affect the cleavage of Notch at the membrane. Their research also uncovered a critical amino acid of the Notch protein that modulates its binding with Serrate.[33] Finally, they helped elucidate the functions of several other proteins involved in the Notch pathway, including the roles of Wasp/Arp2/3,[34] Sec15,[35] Tempura,[36] and EHBP-1[37] in Delta processing and signaling.

References
  1. "Bellen, Hugo J. - DeBakey Awards - Baylor College of Medicine, Houston, Texas".
  2. "Alumni Awards". Archived from the original on 2016-03-05.
  3. "IU's Gill Center honors Hugo J. Bellen and Guoping Feng for achievements in neuroscience".
  4. Bellen, HJ (2014). "Survival of the fittest tools". Genetics. 198 (2): 427–8. doi:10.1534/genetics.114.169110. PMC 4196594. PMID 25316776.
  5. "Science Matters-Blog Archive-What flies tell us about human neurodegenerative disease".
  6. "2020 NAS Election". Retrieved 2020-04-28.
  7. "2020 American Academy of Arts & Sciences Election". Retrieved 2020-04-21.
  8. "Howard Hughes Medical Institute Investigators: Hugo J. Bellen, D.V.M., Ph.D." Retrieved 2014-08-24.
  9. "The Undiagnosed Diseases Network (UDN) | NRI". nri.texaschildrens.org. Retrieved 2019-11-17.
  10. Chen, Kuchuan; Ho, Tammy Szu-Yu; Lin, Guang; Tan, Kai Li; Rasband, Matthew N; Bellen, Hugo J (2016). "Loss of Frataxin activates the iron/sphingolipid/PDK1/Mef2 pathway in mammals". eLife. 5. doi:10.7554/eLife.20732. ISSN 2050-084X. PMC 5130293. PMID 27901468.
  11. Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E, Mirzaa G, Wiszniewski W, Sandoval H, Haelterman NA, Xiong B, Zhang K, Bayat V, David G, Li T, Chen K, Gala U, Harel T, Pehlivan D, Penney S, Vissers LE, de Ligt J, Jhangiani SN, Xie Y, Tsang SH, Parman Y, Sivaci M, Battaloglu E, Muzny D, Wan YW, Liu Z, Lin-Moore AT, Clark RD, Curry CJ, Link N, Schulze KL, Boerwinkle E, Dobyns WB, Allikmets R, Gibbs RA, Chen R, Lupski JR, Wangler MF, Bellen HJ (2014). "A Drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases". Cell. 159 (1): 200–14. doi:10.1016/j.cell.2014.09.002. PMC 4298142. PMID 25259927.
  12. Haelterman NA, Jiang L, Li Y, Bayat V, Sandoval H, Ugur B, Tan KL, Zhang K, Bei D, Xiong B, Charng WL, Busby T, Jawaid A, David G, Jaiswal M, Venken KJ, Yamamoto S, Chen R, Bellen HJ (2014). "Large-scale identification of chemically induced mutations in Drosophila melanogaster". Genome Res. 24 (10): 1707–18. doi:10.1101/gr.174615.114. PMC 4199363. PMID 25258387.
  13. 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 (6): 963–77. doi:10.1016/j.cell.2008.04.039. PMC 2494862. PMID 18555774.
  14. Sandoval H, Yao CK, Chen K, Jaiswal M, Donti T, Lin YQ, Bayat V, Xiong B, Zhang K, David G, Charng WL, Yamamoto S, Duraine L, Graham BH, Bellen HJ (2014). "Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production". eLife. 3: e03558. doi:10.7554/eLife.03558. PMC 4215535. PMID 25313867.
  15. Wang S, Tan KL, Agosto MA, Xiong B, Yamamoto S, Sandoval H, Jaiswal M, Bayat V, Zhang K, Charng WL, David G, Duraine L, Venkatachalam K, Wensel TG, Bellen HJ (2014). "The retromer complex is required for rhodopsin recycling and its loss leads to photoreceptor degeneration". PLOS Biol. 12 (4): e1001847. doi:10.1371/journal.pbio.1001847. PMC 4004542. PMID 24781186.
  16. Zhang K, Li Z, Jaiswal M, Bayat V, Xiong B, Sandoval H, Charng WL, David G, Haueter C, Yamamoto S, Graham BH, Bellen HJ (2013). "The C8ORF38 homologue Sicily is a cytosolic chaperone for a mitochondrial complex I subunit". J Cell Biol. 200 (6): 807–20. doi:10.1083/jcb.201208033. PMC 3601355. PMID 23509070.
  17. Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, Li Z, Hui J, Graham BH, Quintana A, Bellen HJ (2015). "Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration". Cell. 160 (1–2): 177–90. doi:10.1016/j.cell.2014.12.019. PMC 4377295. PMID 25594180.
  18. Venken KJ, 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 (5806): 1747–51. Bibcode:2006Sci...314.1747V. doi:10.1126/science.1134426. PMID 17138868. S2CID 33007215.
  19. Venken KJ, Popodi E, Holtzman SL, Schulze KL, Park S, Carlson JW, Hoskins RA, Bellen HJ, Kaufman TC (2010). "A molecularly defined duplication set for the X chromosome of Drosophila melanogaster". Genetics. 186 (4): 1111–25. doi:10.1534/genetics.110.121285. PMC 2998297. PMID 20876565.
  20. Venken KJ, Schulze KL, Haelterman NA, Pan H, He Y, Evans-Holm M, Carlson JW, Levis RW, Spradling AC, Hoskins RA, Bellen HJ (2011). "MiMIC: a highly versatile transposon insertion resource for engineering Drosophila melanogaster genes". Nat Methods. 8 (9): 737–43. doi:10.1038/nmeth.1662. PMC 3191940. PMID 21985007.
  21. Nagarkar-Jaiswal S, Lee PT, Campbell ME, Chen K, Anguiano-Zarate S, Gutierrez MC, Busby T, Lin WW, He Y, Schulze KL, Booth BW, Evans-Holm M, Venken KJ, Levis RW, Spradling AC, Hoskins RA, Bellen HJ (2015). "A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila". eLife. 4: e05338. doi:10.7554/elife.05338. PMC 4379497. PMID 25824290.
  22. Nagarkar-Jaiswal S, DeLuca SZ, Lee PT, Lin WW, Pan H, Zuo Z, Lv J, Spradling AC, Bellen HJ (2015). "A genetic toolkit for tagging intronic MiMIC containing genes". eLife. 4: e08469. doi:10.7554/elife.08469. PMC 4499919. PMID 26102525.
  23. Littleton JT, Stern M, Schulze K, Perin M, Bellen HJ (1993). "Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca(2+)-activated neurotransmitter release". Cell. 74 (6): 1125–34. doi:10.1016/0092-8674(93)90733-7. PMID 8104705. S2CID 41084119.
  24. Schulze KL, Broadie K, Perin MS, Bellen HJ (1995). "Genetic and electrophysiological studies of Drosophila syntaxin-1A demonstrate its role in nonneuronal secretion and neurotransmission". Cell. 80 (2): 311–20. doi:10.1016/0092-8674(95)90414-x. PMID 7834751. S2CID 13024777.
  25. Verstreken P, Kjaerulff O, Lloyd TE, Atkinson R, Zhou Y, Meinertzhagen IA, Bellen HJ (2002). "Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release". Cell. 109 (1): 101–12. doi:10.1016/s0092-8674(02)00688-8. PMID 11955450. S2CID 11752921.
  26. Verstreken P, Koh TW, Schulze KL, Zhai RG, Hiesinger PR, Zhou Y, Mehta SQ, Cao Y, Roos J, Bellen HJ (2003). "Synaptojanin is recruited by endophilin to promote synaptic vesicle uncoating". Neuron. 40 (4): 733–48. doi:10.1016/s0896-6273(03)00644-5. PMID 14622578. S2CID 14150492.
  27. Hiesinger PR, Fayyazuddin A, Mehta SQ, Rosenmund T, Schulze KL, Zhai RG, Verstreken P, Cao Y, 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 (4): 607–20. doi:10.1016/j.cell.2005.03.012. PMC 3351201. PMID 15907473.
  28. Verstreken P, Ly CV, Venken KJ, Koh TW, Zhou Y, Bellen HJ (2005). "Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions". Neuron. 47 (3): 365–78. doi:10.1016/j.neuron.2005.06.018. PMID 16055061. S2CID 11579820.
  29. Yao CK, Lin YQ, Ly CV, Ohyama T, Haueter CM, Moiseenkova-Bell VY, Wensel TG, Bellen HJ (2009). "A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis". Cell. 138 (5): 947–60. doi:10.1016/j.cell.2009.06.033. PMC 2749961. PMID 19737521.
  30. Nolo R, Abbott LA, Bellen HJ (2000). "Senseless, a Zn-finger transcription factor, is necessary and sufficient for sensory organ development in Drosophila". Cell. 102 (3): 349–62. doi:10.1016/s0092-8674(00)00040-4. PMID 10975525. S2CID 4974695.
  31. Jafar-Nejad H, Acar M, Nolo R, Hacin H, Pan H, Parkhurst SM, Bellen HJ (2003). "Senseless acts as a binary switch during sensory organ precursor selection". Genes Dev. 17 (23): 2966–78. doi:10.1101/gad.1122403. PMC 289154. PMID 14665671.
  32. 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 (2): 247–58. doi:10.1016/j.cell.2007.12.016. PMC 2275919. PMID 18243100.
  33. Yamamoto S, Charng W-L, Rana NA, Kakuda S, Jaiswal M, Bayat V, Xiong B, Zhang K, Sandoval H, David G, Wang H, Haltiwanger RS, Bellen HJ (2012). "A mutation in EGF repeat 8 of Notch discriminates between Serrate/Jagged and Delta family ligands". Science. 338 (6111): 1229–32. Bibcode:2012Sci...338.1229Y. doi:10.1126/science.1228745. PMC 3663443. PMID 23197537.
  34. Rajan A, Tien AC, 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". Nat Cell Biol. 11 (7): 815–24. doi:10.1038/ncb1888. PMC 3132077. PMID 19543274.
  35. 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". Dev Cell. 9 (3): 351–63. doi:10.1016/j.devcel.2005.06.010. PMID 16137928.
  36. Charng WL, Yamamoto S, Jaiswal M, Bayat V, Xiong B, Zhang K, Sandoval H, David G, Gibbs S, Lu HC, Chen K, Giagtzoglou N, Bellen HJ (2014). "Drosophila Tempura, a novel protein prenyltransferase α subunit, regulates Notch signaling via Rab1 and Rab11". PLOS Biol. 12 (1): e1001777. doi:10.1371/journal.pbio.1001777. PMC 3904817. PMID 24492843.
  37. Giagtzoglou N, Yamamoto S, Zitserman D, Graves HK, Schulze KL, Wang H, Klein H, Rogiers F, Bellen HJ (2012). "dEHBP1 controls exocytosis and recycling of Delta during asymmetric divisions". J Cell Biol. 196 (1): 65–83. doi:10.1083/jcb.201106088. PMC 3255984. PMID 22213802.
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