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

	Megan Campbell megan.campbell@bcm.edu BS, Gettysburg College PhD, University of Wisconsin-Madison (Barry Ganetzky) Pubs	Many genes involved in developmental pathways are expressed in post-mitotic cells; however their function at this stage is often unclear. I am interested in determining if these genes play a role in neuronal maintenance and if so, do they function in the canonical developmental pathway or through a novel mechanism to promote neuronal viability.
	Hsiao-Tuan Chao hc140077@bcm.edu BS and BA, University of Texas at Austin PhD, Baylor College of Medicine MD, Baylor College of Medicine Pubs	The advent of whole-exome and whole-genome sequencing has contributed to enormous advances in the diagnosis of rare diseases, with a large proportion of disease genes identified to impact the formation and function of the nervous system. However, with the rapid rate of disease gene discovery we are now faced with increasing numbers of rare variants identified in poorly characterized genes. I am interested in utilizing human sequencing data and Drosophila melanogaster for high-throughout identification and analysis of the fundamental biology of novel genes mediating the pathogenesis of autism spectrum disorders with co-morbid epilepsy. In the absence of overt structural brain malformations, these disorders likely result from dysfunction on a microstructural or cellular level impacting circuit formation and synaptic transmission. Utilizing these disorders to identify pathogenic gene variants and gene networks will provide critical information regarding the formation of neural circuits, regulatory mechanisms of circuit function and synaptic transmission, and potentially open new avenues for therapeutic intervention.
	Hyunglok Chung hyunglok.chung@bcm.edu BS, KAIST, Republic of Korea PhD, KAIST, Republic of Korea 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.
	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.
	Pei-Tseng Lee pei-tseng.lee@bcm.edu BS, Taipei Medical College, Taiwan MS, National Chung Hsing University, Taiwan PhD, National Tsing Hua University, Taiwan (Ann-Shyn Chiang) Pubs	Reactive oxygen species (ROS) are common by-products generated mostly in mitochondria. Excess ROS cause biomolecule damage and will further lead to neurodegeneration. Many neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis are exacerbated by ROS. Oxidative stress due to ROS also contributes to aging, a major risk factor for neurodegenerative diseases. By feeding fruit flies with paraquat, a poison known to increase ROS, we can screen mutants for sensitivity to ROS. This systemic screen allows us to address the cellular mechanisms involved in the response to ROS and increase and assess their contribution to neurodegeneration.
	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.
	Paul Marcogliese paul.marcogliese@bcm.edu BS and BA, Carleton University, Canada PhD, University of Ottawa, Canada 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 BS, Brigham Young University PhD, University of Utah 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 better understand the molecular underpinnings of AD, I seek to better understand basic biological processes that are aberrant in AD patients. Endocytosis is one such process that is is critical for the clearance of molecules that aggregate and cause the neurodegenerative pathogenesis observed in AD, including Aβ42, a protein fragment produced by cleavage of APP. Aβ42 is highly hydrophobic and is thought to be endocytosed through interactions with the lipid transporter, Apolipoprotein E (ApoE). Aβ42 may be incorporated into lipid droplets (LD) in glia which are thought to serve a neuroprotective function by sequestering peroxidated lipids and protecting neurons from reactive oxygen species. While inadequate uptake and degradation of Aβ42 in AD patients leads to protein aggregation and plaque formation, it is unclear the precise role LDs play in Aβ42 sequestration. I am interested in identifying the key molecular components responsible for normal endocytic uptake, sequestration, and degradation of Aβ42 in neurons and glia in an effort to identify new therapeutic targets for AD.

Graduate Students

	Dongxue Mao dmao@bcm.edu BS, Tsinghua University, China 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.
	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 (Horticulture), 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.
	Mumine Senturk senturk@bcm.edu BS (Molecular Biology and Genetics), Bogazici University, Turkey BS (Chemistry), Bogazici University, Turkey Pubs	Genome-wide association studies have identified several integrin pathway components as Alzheimer's disease susceptibility loci. I am interested in identifying new players in the integrin signaling pathway and examining if these players function in neuronal maintenance and aging. Integrins form strong adhesive junctions between tissue layers, a process that is required in the wing to keep the dorsal and ventral cells attached to each other. A loss of adhesion between these two epithelial layers causes wing blisters. To identify additional regulators of the integrin signaling pathway, we performed a morphological screen in the fly wing. Currently, I am investigating the role of one of the hits from the screen in fly nervous system.
	Kai Li Tan ktan@bcm.edu BS, Rutgers University Pubs	Synaptic transmission is a complex process that involves various cellular activities, including but not limited to, protein synthesis and degradation, vesicular and protein trafficking, and fusion and fission of membranes. Orchestrating the different cellular activities is thus important to ensure optimal synaptic function. One key process that determines the efficiency of neuronal transmission is the tightly-regulated neurotransmitter release. My research focuses on how the formation and maintenance of active zones (neurotransmitter release sites) are regulated, in addition to identifying and understanding the mechanisms of novel components in regulating the exocytosis of neurotransmitter-containing vesicle.
	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.
	Berrak Ugur ugur@bcm.edu BS, Bogazici University, Turkey Pubs	Mitochondria are essential for numerous biological processes including ATP production, fatty acid breakdown, Ca²⁺ homeostasis and Fe-S biogenesis. Hence dysfunction of any of these mitochondrial pathways can cause an exceptional phenotypic heterogeneity. To isolate genes that affect nervous system development, function and maintenance, we performed an unbiased, forward genetic screen for essential genes on the Drosophila X-chromosome and isolated 165 genes. 34 of the 165 genes encode mitochondrial proteins that are conserved in humans and loss of these genes in the fly causes multiple variable phenotypes. I am interested in identifying phenotypic patterns in mitochondrial mutants that will help us to understand underlying common molecular mechanisms by which mitochondrial dysfunction leads to neuronal demise and degeneration.
	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 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.