Hugo J. Bellen
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Hugo J. Bellen is a professor at
Baylor College of Medicine Baylor College of Medicine (BCM) is a medical school and research center in Houston, Texas, within the Texas Medical Center, the world's largest medical center. BCM is composed of four academic components: the School of Medicine, the Graduate Sc ...
and an investigator emeritus at the
Howard Hughes Medical Institute The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization based in Chevy Chase, Maryland. It was founded in 1953 by Howard Hughes, an American business magnate, investor, record-setting pilot, engineer, fil ...
who studies
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
and
neurobiology Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, development ...
in the
model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
, ''
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Ch ...
'', the fruit fly.


Education and Career

Hugo Bellen is a Distinguished Service Professor at Baylor College of Medicine (BCM) in the Departments of Molecular and Human Genetics and Neuroscience and an Investigator Emeritus at the Howard Hughes Medical Institute. 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. 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. 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 FlyBase is an online bioinformatics database and the primary repository of genetic and molecular data for the insect family Drosophilidae. For the most extensively studied species and model organism, ''Drosophila melanogaster'', a wide range of ...
, the
NHGRI The National Human Genome Research Institute (NHGRI) is an institute of the National Institutes of Health, located in Bethesda, Maryland. NHGRI began as the Office of Human Genome Research in The Office of the Director in 1988. This Office transi ...
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 Academia Sinica (AS, la, 1=Academia Sinica, 3=Chinese Academy; ), headquartered in Nangang, Taipei, is the national academy of Taiwan. Founded in Nanking, the academy supports research activities in a wide variety of disciplines, ranging from ...
in Taipei, Taiwan, the
KAIST The Korea Advanced Institute of Science and Technology (KAIST) is a national research university located in Daedeok Innopolis, Daejeon, South Korea. KAIST was established by the Korean government in 1971 as the nation's first public, research ...
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 Genetics Society of America (GSA) is a scholarly membership society of more than 5,500 genetics researchers and educators, established in 1931. The Society was formed from the reorganization of the Joint Genetics Sections of the American Soc ...
; 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. He is a member of the American Academy of Arts & Sciences and a member of the National Academy of Sciences..


Research


Neurodegeneration

Dr. Bellen's current research focuses on an effort to decipher the mechanisms by which mutations in specific genes cause
neurodegeneration A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
, 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. To date over 165 genes that cause a neurodegenerative phenotype when mutated have been uncovered by Dr. Bellen's group using this strategy. Many of these genes encode homologues of human genes that are known to cause neurodegenerative diseases, including
amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
(ALS) (Lou Gehrig's disease), Charcot-Marie-Tooth (CMT),
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
(PD),
Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
(AD),
Leigh syndrome Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who fir ...
, 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 A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
and an increasing inability to deal with
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
, which manifests as
lipid droplet Lipid droplets, also referred to as lipid bodies, oil bodies or adiposomes, are lipid-rich cellular organelles that regulate the storage and hydrolysis of neutral lipids and are found largely in the adipose tissue. They also serve as a reservoir ...
s.


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, which led to the generation of a collection of flies carrying molecularly defined duplications for more than 90% of the Drosophila X-chromosome. Hundreds of Drosophila researchers utilize this collection. Most recently his lab created a new
transposable element A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transp ...
(MiMIC) that permits even more downstream manipulations via RMCE (
recombinase-mediated cassette exchange RMCE (recombinase-mediated cassette exchange) is a procedure in reverse genetics allowing the systematic, repeated modification of higher eukaryotic genomes by targeted integration, based on the features of site-specific recombination processes (SS ...
), such as protein tagging and knockdown and large scale
homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
. 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 Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...
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 Reverse genetics is a method in molecular genetics that is used to help understand the function(s) of a gene by analysing the phenotypic effects caused by genetically engineering specific nucleic acid sequences within the gene. The process proce ...
to help to establish their function. His lab was the first to provide ''in vivo'' evidence that
Synaptotagmin 1 Synaptotagmin-1 is a protein that in humans is encoded by the ''SYT1'' gene. Function Synaptotagmins are integral membrane proteins of synaptic vesicles thought to serve as sensors for calcium ions (Ca2+) in the process of vesicular trafficking ...
functions as the main Calcium sensor in synaptic transmission and that Syntaxin-1A plays a critical role in synaptic vesicle (SV) fusion ''in vivo''. His lab showed that Endophilin and
Synaptojanin Synaptojanin is a protein involved in vesicle uncoating in neurons. This is an important regulatory lipid phosphatase. It dephosphorylates the D-5 position phosphate from phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and Phosphatidylinosi ...
control uncoating of SVs, that the V0 component of the
v-ATPase Vacuolar-type ATPase (V-ATPase) is a highly conserved evolutionarily ancient enzyme with remarkably diverse functions in eukaryotic organisms. V-ATPases acidify a wide array of intracellular organelles and pumps protons across the plasma ...
affects SV fusion, that synaptic mitochondria control SV dynamics, and in addition discovered a novel calcium channel involved in SV biogenesis. 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 The Notch signaling pathway is a highly Conserved sequence, conserved cell signaling system present in most animals. Mammals possess four different Notch proteins, notch receptors, referred to as NOTCH1, NOTCH2, Notch 3, NOTCH3, and NOTCH4. The ...
during this process. These discoveries were made by carrying out multiple forward genetic screens using the mutagen,
ethyl methane sulfonate Ethyl methanesulfonate (EMS) is a mutagenic, teratogenic, and carcinogenic organic compound with formula C3H8SO3. It produces random mutations in genetic material by nucleotide substitution; particularly through G:C to A:T transitions induced b ...
, as well as ''P'' elements. They discovered the protein Senseless 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. They also discovered the protein Rumi 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. Finally, they helped elucidate the functions of several other proteins involved in the Notch pathway, including the roles of Wasp/Arp2/3, Sec15, Tempura, and EHBP-1 in Delta processing and signaling.


References


External links


Bellen Lab website Gene Disruption Project website P Recombineering resources website FlyBase
{{DEFAULTSORT:Bellen, Hugo J. Baylor College of Medicine faculty American geneticists Howard Hughes Medical Investigators 1953 births Living people University of California, Davis alumni Members of the United States National Academy of Sciences Fellows of the American Academy of Arts and Sciences