Current Lab Members | Alumni

Principal Investigator

Hugo Bellen
hbellen@bcm.edu
(713) 798-5272

Business Engineer, University of Brussels, Belgium
DVM, University of Ghent, Belgium
PhD, University of California, Davis

CV PubMed

Investigator, Howard Hughes Medical Institute, Baylor College of Medicine
Professor, Departments of Molecular & Human Genetics and Neuroscience, and Program in Developmental Biology

I am interested in (1) providing a better fundamental understanding of the biology that governs the proper function and maintenance of neurons in aging adults (2) developing tools that can be applied to most genes to control transcript and protein levels in adult neurons to assess which proteins are required for neuronal survival and proper function (3) creating genome wide libraries to manipulate most genes in vivo. My lab uses the fruit fly Drosophila melanogaster as a model system because most biological processes are evolutionarily conserved and studies in fruit flies provide many important clues about the aging process in animals and human diseases.

Lab Manager

Karen Schulze
kschulze@bcm.edu
(832) 824-8757

BS, Southwestern University
PhD, Baylor College of Medicine

Pubs

Postdoctoral Fellows

	Scott Barish scott.barish@bcm.edu BS, Hampshire College PhD, Duke University (Pelin Volkan) Pubs	I am interested in modeling disease to uncover the fundamental mechanisms of neuronal biology. Currently, I use the fly eye as model for Alzheimer's Disease to understand how neurons age and respond to oxidative stress. Our lab has shown that oxidative stress causes neurons to produce peroxidated lipids that are shuttles to nearby glial cells and packaged into lipid droplets. In order to better understand this pathway, I am investigating known Alzheimer's Disease risk genes that may be involved in lipid export from neurons. I am also working to understand how chromatin modifying proteins lead to neurodevelopmental disorders.
	Hyunglok Chung hyunglok.chung@bcm.edu BS, KAIST, Republic of Korea PhD, KAIST, Republic of Korea (Kwang-Wook Choi) Pubs	I am part of the Undiagnosed Diseases Network (UDN) team, working towards unraveling the genetic and molecular basis for diseases caused by yet unknown mechanisms. As one of my projects, I am investigating the DMXL1 human gene and its variants identified by Whole-Genome Sequencing (WGS) in a UDN patient. I will determine the potential pathogenicity of DMXL1 variants found in the patient and explore the molecular functions of Rabconnectin-3a, the fly homologue. In addition, as I am particularly interested in the genes associated with developmental signaling pathways such as Hippo (Hpo), Hedgehog (Hh) and Wingless (Wg), I will focus on the UDN cases relevant to these pathways. I am eager to discover the mechanisms by which the variants affect these developmental signaling pathways and mediate the pathogenesis of these rare human diseases.
	Debdeep Dutta debdeep.dutta@bcm.edu BSc, University of Burdwan, West-Bengal, India MSc, Banaras Hindu University, India PhD, Banaras Hindu University, India (Ashim Mukherjee) Pubs	My research interest is to understand the pathobiology of rare and undiagnosed neurological diseases. By taking advantage of next-generation sequencing data of the patients and the success of variant functional assessment using the humanized fruit-fly model, I will identify novel human disease genes. Importantly, I will further dissect the biological mechanisms of these new disease genes with a particular focus on conserved signaling pathways. Unraveling the biology of rare neurological conditions can be immensely helpful for the therapeutic development and proper disease management; and, it will also shed light on more common disease mechanisms.
	Yan Huang yan.huang@bcm.edu BS, Hunan Agricultural University, China MS, Hunan Agricultural University, China PhD, University of Chinese Academy of Sciences, China (Yong Q. Zhang) Pubs	I am interested in unraveling the molecular pathways that underlie rare genetic neurological diseases in infants using Drosophila as a model organism. The fly allows us to efficiently study and analyze the underlying pathogenic mechanisms of these genetic diseases. An in-depth investigation of the affected cellular and molecular pathways allows us to identify molecular targets and sometimes existing drugs that affect these targets and hence allow therapeutic development. These studies often also shed light on much more common diseases like Parkinson's Disease, Alzheimer Disease and Multiple Sclerosis.
	Oguz Kanca oguz.kanca@bcm.edu BS, Bilkent University, Ankara, Turkey PhD, EMBL Heidelberg (Pernille Rørth) Postdoc, Biozentrum, University of Basel (Markus Affolter) Pubs	Whole exome sequencing and personalized medicine prompted the need for efficient methods to test the functionality of gene variants. I am interested in establishing techniques and tools to expedite the analysis of functionality of human gene variants, using the power of Drosophila genetics.
	David Li-Kroeger likroege@bcm.edu BS, University of Cincinnati MS, University of Cincinnati PhD, University of Cincinnati (Brian Gebelein) Pubs	For neurons, maintaining homeostasis in the face of accumulating stress is essential to prevent neurodegenerative diseases. In response to stress, neurons produce survival factors such as the NAD salvage enzyme Nicotinamide mononucleotide adenylyltransferase (Nmnat), which protects neurons from a variety of insults. For example, increased Nmnat protects severed axons from degeneration, protects neurons from chemotherapy agents, and reduces the aggregation of disease causing proteins like hyperphosphorylated Tau. While the varieties of conditions that can be ameliorated by Nmnat suggest a central role for this protein in cellular protection and/or survival, the mechanisms by which Nmnat protects neurons are not fully understood. The aim of my research is to use Drosophila genetics to gain mechanistic insight elucidating Nmnat function.
	Guang Lin guangl@bcm.edu BS, National Taiwan Ocean University MS, National Taiwan Ocean University PhD, Stony Brook University/CSHL (Nicholas Tonks) Pubs	I am interested in studying the molecular function of genes that cause neurodegenerative diseases. In collaboration with other members in the lab, my research has focused on VAPB, frataxin and PLA2G6, which cause Amyotrophic Lateral Sclerosis (ALS), Friedreich's Ataxia (FA) and Neurodegeneration with brain iron accumulations (NBIAs), respectively. We have generated Drosophila loss-of-function mutations for each of them and are currently studying the phenotypes associated with loss of these genes. By studying the molecular mechanisms that underlie the identified phenotypes, we hope to gain insight in the clinical pathology of these neurodegenerative diseases.
	Nichole Link nichole.link@bcm.edu BA, Hendrix College PhD, UT Southwestern Medical Center (John Abrams) Pubs	Nuclear architecture and three-dimensional genome organization are important for maintaining proper gene regulation during development and differentiation. I am interested in the mechanisms that establish chromatin organization within the nucleus and how disruption of nuclear structure results in neuronal disorders.
	Mengqi Ma mengqi.ma@bcm.edu BS, Tongji University, China PhD, Tsinghua University, China (Jose Carlos Pastor-Pareja) Pubs	Early onset rare diseases may be a more severe manifestation of neurodegenerative disorders in advance. I am interested in identifying genes involved in undiagnosed rare diseases using Drosophila as a model. I hope to take advantage of this simplified but sophisticated system to look into conserved mechanisms, so as to help understanding and therapy of the diseases.
	Dongxue Mao dmao@bcm.edu BS, Tsinghua University, China PhD, Baylor College of Medicine (Hugo Bellen) Pubs	Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to muscle atrophy and paralysis. Mutations in VapB cause ALS, but the mechanism is unclear. I am interested in understanding the cellular functions of VapBin order to shed light on how loss of VapB can cause a motor neuron disease using Drosophila melanogaster.
	Paul Marcogliese paul.marcogliese@bcm.edu BS and BA, Carleton University, Canada PhD, University of Ottawa, Canada (David Park) Pubs	I am interested in the discovery and characterization of novel genes involved in a variety of undefined neurological conditions. In attempts to streamline these efforts, I am part of the Undiagnosed Diseases Network (UDN). The UDN uses next-generation sequencing (whole-genome and whole-exome) to determine causative gene variants in these patients. This is followed by rapid generation of Drosophila with strong loss of function alleles in these genes. The characterization of these flies and further examination of the underlying molecular and cellular mechanisms underlying the phenotype in flies may provide vital insight into the human disease.
	Matthew Moulton matthew.moulton@bcm.edu BS, Brigham Young University PhD, University of Utah (Anthea Letsou) Pubs	Research into Alzheimer's disease (AD) has led to the identification of key molecular players in the etiology and pathogenesis of the disease. However, despite tremendous efforts, few effective therapeutic options are available for AD patients. In an effort to identify gene candidates that might prove useful for therapeutic intervention, I seek to better understand the molecular underpinnings of AD. Our lab has demonstrated that proper lipid generation and storage is critical for healthy brain function. While it is clear that under stress conditions, neurons produce lipids that are exported and endocytosed by glia to make lipid droplets (LDs), we do not know all the genes involved in this neuron-to-glia shuttling of lipids. I am undertaking an effort to identify these genes and examine their role in LD formation and clearance of the neurotoxic molecule Aβ42. Aβ42, a protein fragment produced by cleavage of APP, is lipophilic and we predict that it can be endocytosed through the same pathway used to endocytose lipids potentially leading to its sequestration and/or degradation. Thus, the formation of LDs may be beneficial in sequestering toxic species of lipids and proteins and an important pathway to consider for the development AD therapies.

Graduate Students

	Thomas Ravenscroft thomas.ravenscroft@bcm.edu BSc, The University of Manchester Pubs	Neurodegenerative diseases arrise from a multitude of different causes, and can originate in various locations within the nervous system to cause harm. I am interested in understanding what causes certain neuronal populations to have an increased vulnerability to different insults whether they be genetic or environmental. Using the exciting genetic tools at our disposal in Drosophila melanogaster, I aim to learn more about the variances between neuronal populations in terms of their architecture, composition and physiology. Using a common component of all neurons, the sodium channel gene para, and selective targeting of neurons using the UAS-GAL4 system, I aim to identify the components that are unique to specific neurons as well as the consequences when these neurons are depleted.
	Jose Salazar jose.salazar@bcm.edu BS, Texas A&M University Pubs	Alzheimer's disease (AD) affects millions of people in the United States alone. Although genes and mutations that cause early-onset AD have been studied extensively, genetic risk factors of late-onset AD are less understood. I am interested in uncovering the molecular function of TM2D3, a new late-onset AD risk gene, and its related homologs to unravel novel cellular pathways that predispose individuals to AD and related neurodegenerative disorders. I am co-mentored by Shinya Yamamoto.
	Burak Tepe tepe@bcm.edu BSc, Bogazici University, Turkey Pubs	Friedreich's ataxia (FRDA) is the most prevalent form of recessive cerebellar ataxia and it is caused by mutations in Frataxin (FXN). Frataxin (FXN) is required for normal mitochondrial function and intracellular iron homeostasis. We have recently shown a mitochondria independent pathway through iron accumulation, sphingolipid synthesis and ectopic activation of the PDK1/Mef2 signaling leading to neurodegeneration in both Drosophila and mouse models. Currently I am investigating therapeutic potential of manipulating the sphingolipid/PDK1 pathway to suppress the neurodegenerative features caused by loss of FXN. I am co-mentored by Ben Arenkiel.
	Julia Wang julia.wang@bcm.edu BS, University of Michigan, Ann Arbor Pubs	I am interested in combining patient genomic data with Drosophila genetics to understand fundamental biological processes. The etiology of rare diseases is often unknown. Although sequencing data from these patients yield candidate genes, we often lack functional validation. Drosophila and its powerful genetic tools can efficiently validate the disease-causing genetic variants and allow us to pursue the underlying mechanisms of disease. My project involves taking novel candidate disease causing genes from patients and determining pathogenic variants in Drosophila. Furthermore, because many of these candidates lack functional annotation, I hope to dissect their roles in basic biological mechanisms.
	Liping Wang liping.wang@bcm.edu BS, Shanghai Ocean University, China MS, University of Southern California, Los Angeles Pubs	The role of sphingolipid metabolism and endolysosomal dysfunction in neurodegenerative diseases, including Parkinson's disease (PD), is not well understood. My research is focused on the mitochondrial protein Pink1, retromer components Vps26, Vps29, and Vps35, and phospholipase PLA2G6, which are all implicated in PD or Parkinsonism. By utilizing genetic recombinase and the T2A-Gal4 system, I seek to understand sphingolipid metabolism alterations induced by loss of each of these genes. By understanding sphingolipid metabolism alterations in PD-associated mutants, I hope to discover novel pathogenic pathways of PD.