Bellen, D.V.M., Ph.D.
Bellen, D.V.M., Ph.D.
Baylor College of Medicine
- Distinguished Service Professor
Molecular & Human Genetics
Baylor College of Medicine
- Faculty Senator
Baylor College of Medicine
- March of Dimes Chair in Developmental Biology
Baylor College of Medicine
- Chair in Neurogenetics
Jan and Dan Duncan Neurological Research Institute
- MBA from University Of Brussels
- 07/1976 - Brussels, Belgium
- DVM from University Of Ghent
- 07/1983 - Ghent, Belgium
- PhD from University Of California, Davis
- 12/1986 - Davis, California United States
- Post-Doctoral Fellowship at University Of Basel
- 08/1989 - Basel, Switzerland
Honors & Awards
- Member of American Association of Arts and Sciences
- Member of the National Academy of Sciences
- Mitochondria and neuronal degeneration, and technology development
Professional StatementOne of the main aims of the research in my lab is to elucidate the molecular basis of neurodegeneration. Since no unbiased genetic screens in model organisms were performed to sample genes that cause neurodegenerative phenotypes, we embarked on such a screen in fly photoreceptors and isolated 700 mutations corresponding to 165 complementation groups. This screen has provided a very rich resource of novel mutants for the fly community, and has permitted us to dissect mechanisms for a variety of diseases, including Charcot-Marie-Tooth disease, Leigh syndrome and Friedreich’s ataxia. This screen has also led to the identification of mutations in 32 genes that encode proteins that are targeted to mitochondria. By exploring the molecular mechanisms of these rare diseases we were able to determine that biochemical pathways are affected that also play a role in Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Alzheimer’s disease. These pathways are now being studied intensely in the lab.
My lab as well as the laboratories of Michael Wangler and Shinya Yamamoto here at BCM and John Postlethwhait and Monte Westerfield at the University of Oregon were selected by the Undiagnosed Diseases Network (UDN) to direct the Model Organism Screening Center (MOSC) for the UDN of the US. Through close collaborations with human geneticists and physicians, we have identified variants in human genes that are associated with neurological diseases in children. We have so far participated in the discovery of the genetic causes of 17 human diseases in the past three years. We are also studying some of these genes in depth to determine the molecular events that underlie these diseases to identify targets to develop drugs.
My lab also plays an important role in developing new tools to manipulate flies as well as reagents for the fly community. I have been the PI of the Genome Disruption Project (GM067858) for 15 years. The reagents that we have produced include more than 21,000 single transposable element insertion stocks in more than 70 percent of all fly genes. These stocks are currently distributed by the Bloomington Drosophila Stock Center (BDSC). Most recently we created a novel transposable element named MiMIC that allows a staggering array of manipulations of the fly genome in vivo. So far more than 17,000 lines have been created, of which 7,500 have been deposited in the BDSC. We have used these lines to tag 1,000 genes with a multifunctional tag that allow us to determine gene expression patterns in vivo, immunoprecipitations, ChIP and in vivo protein inactivation. Finally, in collaboration with Norbert Perrimon at Harvard, we have developed the CRIMIC technology. This allows us to insert a small multifunctional cassette in almost any gene using CRISPR. We are in the process of inserting these very versatile tags in thousands of genes.
I have excellent resources via the NIH and private foundations, and I am truly dedicated to graduate education and postdoctoral training as is obvious from the success of my former trainees.
- Chung HL, Wangler MF, (...), Herndon MJ, Chen S; Members of Undiagnosed Diseases Network, (...), Bucelli RC, Yamamoto S, Lee HK, Prada CE, Chae JH, Vogel TP, Bellen HJ "Loss- or gain-of-function mutations in ACOX1 cause axonal loss via different mechanisms." Neuron. 2020 106 : 589-606.e6. Pubmed PMID: 32169171
- Link N, Chung H, Jolly A, (...), Lupski JR, Bellen HJ "Mutations in ANKLE2, a ZIKA virus target, disrupt an asymmetric cell division pathway in Drosophila neuroblasts to cause microcephaly." Dev Cell. 2019 51 : 713-729. Pubmed PMID: 31735666
- Şentürk M, Lin G, Zuo Z, Mao D, Watson E, Mikos AG, Bellen HJ "Ubiquilins regulate autophagic flux through mTOR signalling and lysosomal acidification." Nat Cell Biol.. 2019 21 : 384-396. Pubmed PMID: 30804504
- Splinter K, Adams DR, Bacino CA, Bellen HJ, (...), Wangler MF, Westerfield M, Wheeler MT, Wise AL, Worthey EA, Yamamoto S, Ashley EA; Undiagnosed Diseases Network "Effect of genetics diagnosis on patients with previously undiagnosed disease.." N Engl J Med.. 2018 379 : 2131-2139.
- Lin G, Lee PT, Chen K, Mao D, Tan KL, Zuo Z, Lin WW, Wang L, Bellen HJ "Phospholipase PLA2G6, a Parkinsonism-associated gene, affects Vps26 and Vps35, retromer function, and ceramide levels, similar to a-synuclein gain.." Cell Metab. 2018 28 : 605-618.
- Lee PT, Zirin J, Kanca O, (...), Levis RW, Spradling AC, Perrimon N, Bellen HJ "A gene-specific T2A-GAL4 library for Drosophila." eLife. 2018 7 : e35574.
- Tan KL, Haelterman NA, (...), Milewicz DM, Bellen HJ "Ari-1 regulates myonuclear organization together with Parkin and is associated with aortic aneurysms.." Dev Cell.. 2018 45 : 226-244.
- Liu L, MacKenzie KR, Putluri N, Maletic-Savatic M, Bellen HJ "The glia-neuron lactate shuttle and elevated ROS promote lipid synthesis un neurons and lipid droplet accumulation in glia via APOE/D.." Cell Metab.. 2017 26 : 719-737.
- Ugur B, Bao H, Stawarski M, (...), Macleod GT, Chapman ER, Bellen HJ "The Krebs cycle enzyme Isocitrate Dehydrogenase 3A Couples mitochondrial metabolism to synaptic transmission." Cell Rep.. 2017 21 : 3794-3806.
- Yoon WH, Sandoval H, Nagarkar-Jaiswal S, Jaiswal M, Yamamoto S, Haelterman NA, (...), Wangler MF, Karaca E, Lupski JR, Bellen HJ "Loss of Nardilysin, a mitochondrial co-chaperone for α-ketoglutarate dehydrogenase, promotes mTORC1 activation and neurodegeneration." Neuron. 2017 93 : 115-131.
- Chen K, Ho TS, Lin G, Tan KL, Rasband MN, Bellen HJ "Loss of Frataxin activates the iron/sphingolipid/PDK1/Mef2 pathway in mammals.." eLife. 2016 5 : e20732.
- Bellen HJ, Yamamoto S "Morgan's legacy: fruit flies and the functional annotation of conserved genes.." Cell. 2015 163 : 12-14.
- Jaiswal M, Haelterman NA, Sandoval H, Xiong B, Donti T, Kalsotra A, Yamamoto S, Cooper TA, Graham BH, Bellen HJ "Impaired mitochondrial energy production causes light induced photoreceptor degeneration independent of oxidative stress." PLoS Biol. 2015 July 15; 13 : e1002197. Pubmed PMID: 26176594
- Nagarkar Jaiswal S, Lee P-T, Campbell ME, Chen K, Anguiano-Zarate S, Cantu Gutierrez M, Busby T, Lin W-W, He Y, Schulze KL, Booth BW, Evans-Holm M, Venken KJT, Levis RW, Spradling AC, Hoskins, RA, Bellen HJ "A library of MiMICs allows tagging of genes and reversible spatial and temporal knockdown of proteins in Drosophila." eLife. 2015 March 31; : 4. Pubmed PMID: 25824290
- Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, Li Z, Hui J, Graham BH, Quintana A, Bellen HJ "Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration." Cell. 2015 January 15; 160 : 177-90. Pubmed PMID: 25594180
- Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E, et al. "A Drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases." Cell. 2014 September 25; 159 (1): 200-14. Pubmed PMID: 25259927
- Xiong B, Bayat V, Jaiswal M, Zhang K, Sandoval H, Charng WL, Li T, David G, Duraine L, Lin YQ, Neely GG, Yamamoto S, Bellen HJ "Crag Is a GEF for Rab11 Required for Rhodopsin Trafficking and Maintenance of Adult Photoreceptor Cells." PLoS Biol. 2012 December ; 10 (12): e1001438. Pubmed PMID: 23226104
- Yamamoto S, Charng WL, Rana NA, Kakuda S, Jaiswal M, Bayat V, Xiong B, Zhang K, Sandoval H, David G, Wang H, Haltiwanger RS, Bellen HJ "A mutation in EGF repeat-8 of Notch discriminates between Serrate/Jagged and Delta family ligands." Science. 2012 November 30; 338 (6111): 1229-32. Pubmed PMID: 23197537
- Venken KJ, Schulze KL, Haelterman NA, Pan H, He Y, Evans-Holm M, Carlson JW, Levis RW, Spradling AC, Hoskins RA, Bellen HJ "MiMIC: a highly versatile transposon insertion resource for engineering Drosophila melanogaster genes." Nat. Methods. 2011 8 (9): 737-43. Pubmed PMID: 21985007
- Tsuda H, Han SM, Yang Y, Tong C, Lin YQ, Mohan K, Haueter C, Zoghbi A, Harati Y, Kwan J, Miller MA, Bellen HJ "The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors." Cell. 2008 June 13; 133 (6): 963-77. Pubmed PMID: 18555774
- Zhai RG, Zhang F, Hiesinger PR, Cao Y, Haueter CM, Bellen HJ "NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration." Nature. 2008 April 17; 452 (7189): 887-91. Pubmed PMID: 18344983
- Acar M, Jafar-Nejad H, Takeuchi H, Rajan A, Ibrani D, Rana NA, Pan H, Haltiwanger RS, Bellen HJ "Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling." Cell. 2008 January 25; 132 (2): 247-58. Pubmed PMID: 18243100
- Venken KJ, He Y, Hoskins RA, Bellen HJ "P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster." Science. 2006 December 15; 314 (5806): 1747-51. Pubmed PMID: 17138868
- Hiesinger PR, Fayyazuddin A, Mehta SQ, Rosenmund T, Schulze KL, Zhai RG, Verstreken P, Cao Y, Zhou Y, Kunz J, Bellen HJ "The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila." Cell. 2005 May 20; 121 (4): 607-20. Pubmed PMID: 15907473
- Verstreken P, Kjaerulff O, Lloyd TE, Atkinson R, Zhou Y, Meinertzhagen IA, Bellen HJ "Endophilin mutations block clathrin-mediated endocytosis but not neurotransmitter release." Cell. 2002 April 5; 109 (1): 101-12. Pubmed PMID: 11955450
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