Email

hbellen@bcm.edu

Positions

Distinguished Service Professor

Molecular & Human Genetics and Neuroscience
Baylor College of Medicine

Chair in Neurogenetics

Jan and Dan Duncan Neurological Research Institute

March of Dimes Chair in Developmental Biology

Baylor College of Medicine

Faculty Member

Graduate Programs in Development, Disease Models, and Therapeutics; Genetics & Genomics; and Neuroscience
Baylor College of Medicine

Faculty Senator

Baylor College of Medicine

Education

MBA from Université Libre de Bruxelles

07/1976 - Brussels, Belgium

Solvay Brussels School Economics & Management

DVM from Ghent University

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 biochemical pathways 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 were selected by the Undiagnosed Diseases Network (UDN) as the Drosophila Model Organism Screening Center (MOSC). Through close collaborations with human geneticists and physicians, we have identified variants in numerous human genes that are associated with neurological diseases in children. We have participated in the discovery of the genetic causes of 60 human diseases in the past ten 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 and have been successful in identifying FDA approved drugs for four diseases.

My lab also plays an important role in developing new tools to manipulate flies and to generate reagents for the fly community. I have been the PI of the Gene Disruption Project for more than 20 years. The reagents that we have produced include more than 25,000 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 allows 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 and have generated more than 3,500 tagged genes so far. We have excellent resources via NIH and private foundations.

Websites

Selected Publications

• Yamamoto S, Kanca O, Wangler MF, Bellen HJ "Integrating non‑mammalian model organisms in the diagnosis of rare genetic human disease." Nat Rev Genet.. 2024 Jan;25:46–60. Pubmed PMID: 37491400
• Goodman LD, Ralhan I, Li X, Lu S, Moulton MJ, Park YJ, Zhao P, Kanca O, Ghaderpour ZS, Jacquemyn J, Shulman JM, Ando K, Sun K, Ioannou MS, Bellen HJ "Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress." Nat Neurosci.. 2024 Oct;27:1918–1933. Pubmed PMID: 39187706
• Dutta D, Kanca O, Byeon SK, Marcogliese PC, Zuo Z, Shridharan RV, Park JH, Lin G, Ge M, Heimer G, Kohler JN, Wheeler MT, Kaipparettu BA, Pandey A, Bellen HJ "A defect in mitochondrial fatty acid synthesis impairs iron metabolism and causes elevated ceramide levels." Nat Metab.. 2023 Sep;5:1595–1614. Pubmed PMID: 37653044
• Chung HL, Ye Q, Park YJ, Zuo Z, Mok JW, Kanca O, Tattikota SG, Lu S, Perrimon N, Lee HK, Bellen HJ "Very‑long‑chain fatty acids induce glial‑derived Sphingosine‑1‑Phosphate synthesis, secretion, and neuroinflammation." Cell Metab.. 2023 May;35:855–874. Pubmed PMID: 37084732