Email

hbellen@bcm.edu

Positions

Professor

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

Education

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

Professional Interests

• Mitochondria and neuronal degeneration, and technology development

Professional Statement

One 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.

Websites

Selected Publications

• 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.