Center for Genomics of Neurodegenerative Disease Phatnani Lab
The Center for Genomics of Neurodegenerative Disease (CGND) is dedicated to the study of neurodegenerative diseases such as ALS and Alzheimer’s disease. CGND’s vision is to establish a center for applying state of the art genetics, genomics and bioinformatics to the study of neurodegenerative disease mechanisms.
CGND’s goals are to use whole genome sequencing to identify mutations that cause neurodegenerative disease. To gain insights into the relationship between mutations, gene expression and disease mechanisms, whole genome sequencing data will ultimately be integrated with other genomic-scale data such as RNA-SEQ, RNA-protein interactions, and DNA methylation patterns.
CGND is helping to create a uniform system of collecting clinical annotation to better enable the integration of genomic data with clinical profiles. This information will be freely available to the research community in a data warehouse for whole genome sequencing and RNA-SEQ analyses.
+Hemali Phatnani, PhD
Hemali Phatnani, PhD, serves as the Director of the Center for Genomics of Neurodegenerative Disease (CGND) at NYGC. She has a joint appointment as Adjunct Assistant Professor of Neurogenetics in the Department of Neurology and the Institute for Genomic Medicine at Columbia University. Her research focuses on gene regulatory mechanisms that underlie the complex interactions between motor neurons and non-neuronal cells in the spinal cord of ALS mouse models, including astrocytes, microglia and oligodendrocytes. The goal of Dr. Phatnani’s research is to apply state-of-the-art genomics and bioinformatics to understand the role of cell-cell interactions in ALS pathophysiology.
Dr. Phatnani carried out her postdoctoral studies in Dr. Tom Maniatis’ Lab at Harvard and Columbia Universities, where she studied ALS disease mechanisms using stem cell-derived motor neurons and genomic profiling methods. She established a novel cell culture system to study cell intrinsic and cell extrinsic effects of astrocytes on motor neuron gene expression, and discovered a complex interplay between the two cell types during ALS disease progression.
Dr. Phatnani received her PhD in biochemistry and molecular biology at Duke University, where she characterized the interactions between RNA polymerase and proteins involved in the mechanistic coupling of RNA transcription and processing. She earned a B.Sc. in life sciences from Bombay (Mumbai) University.
+Genetics and Genomics of ALS
The vision of the Center for Genomics of Neurodegenerative Disease (CGND) at NYGC is to establish a framework to apply state-of-the-art genomics and bioinformatics to the study of neurodegenerative disease mechanisms, by building partnerships with clinicians, basic scientists, geneticists, and computational biologists.
The CGND’s research program in Amyotrophic Lateral Sclerosis (ALS) was established with the help of generous support from The Tow Foundation and The ALS Association’s (ALSA) Greater New York Chapter. The CGND’s partners include not only NYGC’s founding members such as Columbia and Rockefeller, but also ALS centers throughout the northeast, such as the University of Pennsylvania, Massachusetts General Hospital and Hershey Medical Center at Penn State University, among others. Through the support of ALSA, our efforts also synergize with other ALSA-funded consortia, such as Answer ALS, and the GTAC (“Genomics Translation for ALS Clinical care”) consortium. In addition, we work in close partnership with Target ALS’s Post Mortem Core, iPS core, and Biospecimen Collection.
Through a multidisciplinary collaborative effort that spans multiple ALS centers and bridges ALS clinicians and scientists, we are using whole genome sequencing to discover and study mutations and mechanisms underlying ALS. Broadly stated, the goals of this consortium are the following:
Integrate whole genome sequencing with RNA sequencing to interrogate relationships between mutations, gene expression and disease mechanisms
RNA sequencing analyses combined with whole genome sequencing will help us to identify how changes in DNA are expressed in the brain and spinal cord, and how this affects the presentation and course of disease.
Integrate genomic and clinical data to identify genetic modifiers of disease onset/progression/presentation
Our partners’ clinical phenotyping efforts will enable us to sequence well-stratified patient cohorts, so that we can eventually identify mutations that are associated with different forms of the disease, or gene variants that can modify the presentation of the disease and could be further studied to identify pathways for the targeted development of therapies.
Create and maintain a data warehouse for genomic data that can be broadly accessed by the academic community
Our sequencing data will be made freely available to the research community. Resource and data sharing is an integral aspect of our efforts, because we want the data that we generate to be as useful as possible to as many researchers as possible. Broad sharing will only accelerate the pace of discovery and therapeutics, which are crucially needed in ALS.
Such broad sharing and collaborative efforts are ultimately geared towards making the best use of sequencing data. For example, comparing clinical profiles to genomic profiles can enable us to determine whether specific mutations are associated with specific clinical outcomes – this may ultimately make truly “personalized” medicine possible.
Design and create ALS models to test effects of mutations in stem cell derived neurons and in mouse models using state-of-the-art genomic manipulation methods.
To study the function of any sequence variants that we identify and to understand how they affect disease mechanisms, we collaborate with our research partners to make new models of disease such as iPS cells and mouse models. We use these models to study, for example, how mutations affect the different cell types that are known to play a role in ALS, such as astrocytes, microglia, and oligodendrocytes, all of which are known to affect motor neurons in ALS. Using these models, we examine regulatory mechanisms affecting the transcriptome, as well as mechanisms underlying intercellular interactions in disease. To further these analyses, we are developing tools to integrate the experimental and computational analysis of large-scale data that includes transcriptomes of specific cell types in the Central Nervous System, profiles of RNA-binding proteins implicated in disease, and high-resolution imaging. The combination of new deep sequencing methods, sample acquisition, data analysis pipelines, and molecular and phenotypic characterizations using new mouse models will provide mechanistic insights that were previously not possible.
Any models that we develop through our collaborative efforts will be made freely available to the research community – this is in fact a condition of any partnerships that we undertake. In addition, the conceptual framework and infrastructure should be widely applicable to other neurodegenerative diseases.
The CGND’s ALS Consortium at-a-glance:
- Membership: Columbia University Medical Center, University of Pennsylvania, Massachusetts General Hospital, Hershey Medical Center at Pennsylvania State University, University of Maryland, Johns Hopkins University, Henry Ford Health System, University of California at San Francisco, MIT, Academic Medical Center, University of Amsterdam
- Pre-competitive Data Sharing with all Consortium Members, samples consented for broad sharing for all medical research
- Partnerships: Answer ALS Consortium, GTAC Consortium, Target ALS – Post Mortem Core, iPS Core, Biospecimen Collection
- Target Groups: FALS, SALS, C9 carriers
- Data being collected now: DNA, autopsy tissue RNA, some iPS, clinical data (longitudinal clinical data targeted for ~1300 of a total of 1800 patients)
- ALS gene discovery efforts: unexplained familial ALS, increasing power through increased numbers of sporadic patients for co-analysis with existing datasets
- Genotype-phenotype correlations
- Integrating WGS with tissue-specific transcriptomics for understanding the impact of regulatory variation and cell type-specific contributions
- C9 promoter methylation (QTLs of this phenotype)
+Astrocytes in ALS
How neurons and glia communicate and depend on each other is still a largely open question in neuroscience. Perturbations in this interdependence underlie many neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS). Motor neuron death in ALS is a culmination of pathological processes affecting both glia, such as astrocytes, and neurons. Although astrocytes are known to contribute to motor neuron death in ALS, the mechanisms through which they do so are not well understood. Our lab has pioneered a motor neuron-astrocyte co-culture platform (‘sandwich culture’) that allows us to dissect how motor neurons and astrocytes interact over time and how these interactions are affected in disease. It is known that expressing an ALS causing human transgene (SOD1 G93A) in either cell type causes a reciprocal up-regulation of Transforming Growth Factor Beta (TGF-ß) signaling genes between the two cell types. TGF-ß signaling is implicated in many neurodegenerative diseases including sporadic and familial ALS. We are currently investigating the pathological significance of dysregulation of this pathway is SOD1 G93A and FUS ALS models.
+Detecting Repeat Expansions
Several recent studies have identified a specific type of genetic mutation called a repeat expansion (RE) in chromosome 9 open reading frame 72 (C9orf72) to be the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). This type of mutation is common in neurodegenerative diseases; the RE in ALS-FTLD consists of six base pairs (GGGGCC) repeated 100’s to 1000’s of times. Among C9orf72 RE patients, there is considerable heterogeneity in age of onset, disease severity, phenotypic presentation, and the total length of the RE. Several potential mechanisms of disease related to the C9orf72 RE have been proposed: aberrant RNA splicing and translocation, aggregation of dipeptides resulting from non-ATG mediated translation, nucleocytoplasmic export dysfunction, and neuronal branching defects. The length of RE necessary to cause these functional abnormalities and its relationship to disease presentation, however, remain unclear. At NYGC, James is using cutting edge molecular biology and next generation sequencing to investigate the C9orf72 RE and its contribution to ALS-FTLD.
+Cell Type Specific Translatomics
We are also taking ‘functional genomics’ approach to ALS disease progression in vivo by developing biochemical protocols and bioinformatics pipelines to interrogate transcriptome, translatome and epigenome dynamics in a cell type-specific manner in mouse models of ALS. The computational integration of these datasets will decipher the inter-cellular communication and intra-cellular responses during disease advancement at high temporal resolution. These molecular insights will form a fundamental basis for the discovery of new disease biomarkers, and to identify targets for next-generation therapeutics including antisense oligonucleotides to modulate RNA levels, splicing or post-transcriptional regulation.
+Cell Type Specific Transcriptomics
Dynamic regulation of gene expression is a key feature of virtually all aspects of cellular function. Changes in gene expression patterns can reveal the presence of disease, and understanding such changes can yield insight into the basic biology of disease. Recent rapid advances in sequencing technologies have dramatically enhanced our ability to collect gene expression data. However, using the most widely available high throughput sequencing methods, measurement of gene expression in complex tissues is hampered by the need to homogenize or dissociate the tissues. In both cases, positional information is lost. The few high throughput methods for measuring gene expression while preserving spatial information that exist are prohibitively complex, labor intensive, expensive, and require specialized equipment. Thus, a need exists for technologies with which to capture high content spatial gene expression data, that are easier, cheaper, and more widely usable than existing technologies. Studies of neurodegenerative diseases in particular can benefit immensely from a better understanding of how gene expression differs across tissues, cell types, and sub-cellular domains. Motor neurons, the key affected cell type in ALS, can be on the order of a meter long. Such large cells must precisely control not only the amount, but also the localization of RNAs and proteins along that length to function properly. Moreover, subpopulations of motor neurons residing near each other can exhibit different levels of vulnerability to the disease. Substantial evidence now indicates that ALS disease progression involves signaling between neurons and glia, but the nature of this signaling and how it is involved in the spread of the disease state along the spinal cord remain poorly understood. Thus, a better view of how cells of the spinal cord alter the expression of their genes across both spatial and temporal dimensions during disease progression will inform our understanding of ALS. We are developing and utilizing microscopy and molecular techniques in efforts to understand the changes in gene expression patterns that occur in ALS.
James has a broad research background in molecular biology, biochemistry, protein engineering, microbiology, and immunology. He completed his bachelor of science in biochemistry at Miami University (Oxford, OH) in 2002 followed by a year as a research associate in Mason Freeman’s laboratory at Massachusetts General Hospital where he studied innate immune pathways. He received his Ph.D. in biology from the University of California, San Diego in 2009 for his studies on the spatial and temporal regulation of bacterial cell division conducted in Kit Pogliano’s laboratory. As a postdoctoral fellow with Stephen Mayfield, also at UCSD, James developed inexpensive malaria transmission blocking vaccines using a novel algal expression platform. He was awarded the Blasker Science and Technology fellowship for this work and PLoS ONE selected his first publication describing algal-produced vaccine for malaria as one of the most influential papers on tropical medicine and malaria in 2012. He continued these studies as an Instructor at the Icahn School of Medicine at Mount Sinai (New York, NY) with Cecilia Berin, where he re-purposed the algal platform for oral vaccines and protein therapeutics.
Silas’ work is focused on developing tools for understanding how changes gene expression relate to disease at the cellular and sub-cellular level in the context of intact tissues. In this effort, he draws upon expertise gained in bio-tech and academic labs, and training in many areas from robotics, to molecular biology, to microscopy. Dr. Maniatis received his PhD from Harvard University, where he utilized high throughput sequencing and automated behavioral techniques to study the involvement of non-coding RNAs in long term memory formation.
Nadia completed her bachelor of science in bacteriology at University of Wisconsin, Madison in 2001. She spent four years working as a research assistant at the Institute of Human Virology in Baltimore Maryland, where she honed her skills in molecular biology and immunology and assisted in the publication of five manuscripts. She was a recipient of Fogarty fellowship and spent three months in Jos, Nigeria, working with HIV(+) mothers on a project to educate women about mother to child transmission of HIV. After being accepted to a graduate program in biotechnology at Columbia University, Nadia relocated to NYC and secured a research assistant position in Dr. Richard Axel’s laboratory. While pursuing her MA part time, Nadia acquired new skills such as ES cell targeting, development of behavioral animal models and construction of vectors for in vivo and in vitro experiments. After receiving her MA, Nadia accepted a lab manager position in Dr. Charles Zuker’s lab, where she managed a lab of over 20 people, performed ES cell targeting for the lab, managed and supervised a mouse colony of 1000 cages.
Duyang Kim is the Clinical Research Coordinator II at the Center for Genomics of Neurodegenerative Disease (CGND). Her role encompasses coordinating multi-center clinical research projects initiated by CGND and various collaborators across the country. She received her BS in Brain, Behavior, and Cognitive Sciences from the University of Michigan – Ann Arbor in 2006 and her Master of Public Health (MPH) degree in Sociomedical Sciences from Columbia University in 2011. Prior to joining NYGC, she has worked at the New York City Department of Health and Mental Hygiene conducting Chronic Hepatitis C investigations, and the Mount Sinai Beth Israel conducting Phase I-IV industry-sponsored drug and device trials.
Kristy Kang is the Associate Scientist II at the Center for Genomics of Neurodegenerative Disease (CGND). She supports CGND’s diverse projects in a role upstream of NGS data acquisition and works closely with all members of CGND and various collaborators on ongoing research projects. Prior to joining NYGC, she has worked in a cancer research laboratory. She studied the PI3K signaling pathway and the role it plays in thyroid physiology and pathophysiology to discover potential therapeutic approaches for advanced thyroid cancer. Her current research interests include next-generation sequencing technologies, translational medicine and precision medicine. Kristy received her BS in Biological Sciences and Psychology from Carnegie Mellon University.
Delphine has combined molecular genetics and computational approaches to understand the role of several flavors of non-coding RNAs (lncRNAs, piRNAs, miRNAs, esiRNAs) in regulating gene expression during development and disease, in particular cancer. Her work has focused on fertility, reproduction and sex determination. She aims to better our understanding of gender differences in disease. Delphine obtained her PhD in Molecular and Cellular Biology from Strasbourg University in France. She trained at Stanford and the Pasteur Institute in Paris, then joined the Genomics Division of the Cold Spring Harbor Laboratory, New York. Most recently, she also served as a laboratory mentor at OSU, Columbus, OH.
Isabel Hubbard is an Associate Scientist II at the Center for Genomics of Neurodegenerative Disease (CGND). Prior to joining the NYGC, she was a development scientist at a clinical reference laboratory, where she developed targeted oncology assays for the Illumina MiSeqDx and Ion PGM NGS platforms for use in patient molecular diagnostics. Isabel received a BS in Biological Sciences-Neuroscience Track from Carnegie Mellon University in 2013 and an MSc in Biomedical Sciences from University College London in 2014, where her thesis work involved investigating the underlying molecular and genetic pathways of the neuronal ceroid lipofuscinoses (NCLs), a group of early onset neurodegenerative disorders, under the supervision of Dr. Sara Mole at the MRC Laboratory for Molecular Cell Biology.
+POST-DOC AND GRADUATE STUDENTS
Cat finished her undergraduate degree in Biology at Mount Holyoke College, where she worked in the laboratory of Professor Craig Woodard. There, she investigated the effects of hAPP, hParkin, and Pink1 expression in a Drosophila melanogaster model of Sporadic Inclusion Body Myositis. After graduating Mount Holyoke in Spring 2011, she joined the John Lab at The Jackson Laboratory. There, Catherine was involved in several projects that investigated the neurodegenerative aspect of glaucoma pathology. Her primary project was aimed at elucidating the role that the complement system plays in the neuropathology of glaucoma, as well as other neuroinflammatory processes in the optic nerve and retina.
In 2014, Catherine enrolled in the Neurobiology and Behavior PhD Program at Columbia University, and is currently being co-mentored by Dr. Tom Maniatis and Dr. Hemali Phatnani. Her current project focuses on understanding the interactions between astrocytes and motor neurons in G93A ALS and how these cells influence each other via TGF-B signaling.
Güney’s research in CGND aims to understand how RNA localization and dynamics go awry in motor neurons and non-neuronal cells during ALS progression. Her previous work on the role of coding and noncoding RNAs in synaptic plasticity sparked her interest in RNA-based mechanisms underlying neurodegeneration.
She pursued her Ph.D. studies in the lab of Prof. Erin Schuman at the Max-Planck Institute for Brain Research, Frankfurt, where she established the visualization of newly synthesized RNA in neurons using click chemistry approach, developed a fluorescence sensor to visualize the activity-dependent localized microRNA maturation with her collaborators and she was a member of the team which identified neural circular RNAs.
+Dayanne Martins de Castro
Dayanne is a PhD student in the Biology Program at New York University. Her research focuses on the development of computational methods to integrate multiple data sources, such as chromatin accessibility and gene expression, in order to build accurate models of gene regulation in mammalian systems. She is particularly dedicated to understanding transcriptional misregulation in astrocytes and motor neurons in ALS in order to define drivers of neurodegeneration as disease progresses. Prior to joining NYU, Dayanne received her Bachelor’s in Biology from the University of Campinas in Brazil. As an undergraduate, she worked on the development of tools for genetic manipulation of Propionibacteria, a non-model organism of great interest for sustainable production of a petrochemical intermediate. She also spent a year at the University of Pennsylvania, where she focused her studies in Biotechnology. She then joined Amgen as an intern, where her project was focused on computational prediction of biophysical instability in candidate molecules for drug development.
Ian Laster graduated Columbia University with a BS in May 2014 and chose to gain research experience in our lab before applying to medical school. He joined the lab in December 2014 and works closely with Dr. Jan Bergmann on cell-type specific translatomics in the spinal cord.
Rawan Abdelaal works on the interactions between motor neurons and glial cells in ALS pathology using mouse and iPS cell-based models combined with NGS technology. She mostly focuses on iPSC culture systems including differentiation of iPSCs into ALS relevant cell types (e.g. motor neurons, astrocytes, etc.) as well as organization of multiple lines of ALS patient-derived iPSCs and differentiated cells. Rawan graduated with a BS in Biotechnology from the City College of New York in Fall 2015.
Kenneth is an undergraduate student at Columbia University on the pre-medicine track and will graduate in 2017. He volunteers his time to focus on using computational methods and working with ALS-relevant cell populations (e.g. motor neurons, astrocytes, etc.) to understand the cell-type specific transcriptomics of disease progression over time in the SOD1-G93A mouse model of ALS.
+Robert Darnell, MD, PhD
Robert B. Darnell, M.D., Ph.D., is Founding Director and CEO of the New York Genome Center. He also serves as the Robert and Harriet Heilbrunn Professor and Senior Attending Physician at The Rockefeller University and an Investigator of the Howard Hughes Medical Institute. In 2014 he was elected a Member of the National Academy of Sciences and has been a Member of the National Academy of Medicine since 2010. He is also member of the Association of American Physicians and a Fellow of the American Association for the Advancement of Science.
He has received numerous awards, including the Derek Denny-Brown Young Neurological Scholar Award, the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, the NIH Director’s Transformative Research Award in 2012, and the NINDS Research Program Award in 2016.
Dr. Darnell’s academic work began with studies of patients with rare disorders triggered by naturally occurring anti-tumor immune responses that he discovered are caused by antigen-specific killer T cells, laying the groundwork for the field of immuno-oncology. His analysis of the target antigens led him to discover brain-specific systems governing the regulation of RNA, the transcribed copies of our genes. He developed CLIP, a new platform technology that is being widely applied in neurobiology, cancer and inflammatory disease. His work at the New York Genome Center is focused on harnessing the revolution created by the recent dramatic cost reduction in genomic sequencing as well as rapidly advancing information and other technology, utilizing those advances to transform healthcare. He works with the 12 Institutional Founding Members and a growing list of Associate Members from academia and industry including IBM to help develop tools capable of analyzing the massive amounts of data genomic sequencing produces into clinically actionable outcomes. He is Principle Investigator on NYGCs NIH Center for Common Disease Genomics Grant from the National Human Genome Research Institute, the Accelerating Medicines Partnership grant from the National Institute of Arthritis and Musculoskeletal Diseases, and the Sohn Foundation Grant for Pediatric Cancer Research.
Dr. Darnell has studied and worked at a number of the New York Genome Center’s Institutional Founding Members, including Columbia University, The Mount Sinai School of Medicine, Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, The Jackson Laboratory and The Rockefeller University. He has been involved with the growth and advancement of the New York Genome Center since its inception in 2010, as a member of the original group of New York scientists that helped to shape NYGC’s early direction.
+Cheryl A. Moore
Cheryl A. Moore serves as President and Chief Operating Officer at the New York Genome Center. Ms. Moore is responsible for the financial and operational functions of the Genome Center, partnering with Robert B. Darnell, Chief Executive Officer and Founding Director, to set strategic direction and make key decisions for the organization.
Ms. Moore has a long history and extensive experience in leading research organizations. Before joining NYGC, she served for six years as the Executive Vice President and Chief Operating Officer of the Howard Hughes Medical Institute (HHMI), a $19B medical research organization, where she led collaborative strategic efforts and supervised key operational functions. From 2004 until 2010, Ms. Moore served as the founding Chief Operating Officer of HHMI’s Janelia Research Campus, an innovative hub in Northern Virginia, where she played a pivotal role in Janelia’s startup. At Janelia, Ms. Moore guided development and implementation of its operating strategy, overseeing all operational aspects of the campus and its $100+ million annual budget.
Prior to joining HHMI, Ms. Moore served as Senior Vice President and Chief Operating Officer of the Sanford-Burnham Medical Research Institute in La Jolla, CA and previously held top management positions in both start-up and public healthcare companies that experienced intense periods of growth. Prior to her work in biomedical research, she served as a C-Suite leader at a healthcare company which grew from $5M to $1B over five years through acquisitions, and then helped the company prepare for its Initial Public Offering (IPO).
With her diverse experience as both a founder and change leader in the for-profit and nonprofit arenas, Ms. Moore is known for her strategic ability to resolve performance bottlenecks, develop innovation intense environments, implement systems, and rationalize operations. Throughout her career, she has applied these skills across organizations at differing levels of maturity in the fields of healthcare, technology, biomedical research, and financial services, bringing more than 20 years of strategic executive experience in collaborative leadership involving some of the world’s highest-performing scientists and physicians.
Ms. Moore has long played a leadership role in community and industry activities. She currently serves as Chair of the Wellcome Trust Centres Review Committee, and has served as Co-Chair of the Board of the Economic Club of Washington, DC. Ms. Moore served on the Virginia Governor’s Bioscience Strategic Initiatives Task Force, and was appointed by the Governor to the Virginia Biotechnology Research Park Authority Board. She also served on the Advisory Boards of the Human Vaccines Project, the Krasnow Institute for Advanced Study at George Mason University, the Virginia campus of George Washington University, and the Virginia Biotechnology Association. Previously, she served on the Board of the Association of Independent Research Institutes, and was appointed by the Virginia Secretary of Technology to serve on the Grant Allocation Committee of the Commonwealth Technology Research Fund.
Ms. Moore has been honored as one of the top 25 “Women Who Mean Business” by the Washington Business Journal and has also been nominated for the Athena Pinnacle Award, honoring women who forge paths of leadership.
Outside of her professional roles, Ms. Moore enjoys strength training, running, hiking, walking, being outdoors, eating great food, enjoying theater and the arts, travel, boating, and spending time with friends and family. She’s excited to join the New York Genome Center community and looks forward to exploring all that New York has to offer.
+Tom Maniatis, PhD
Scientific & Clinical Steering Committee Chair | Columbia University
Tom Maniatis is a cofounder of the New York Genome Center, and one of the pioneers of modern molecular biology, having led the development of recombinant DNA methods and their application to the study of the mechanisms of gene regulation. He coauthored the definitive laboratory manual on genetic engineering, the Molecular Cloning Manual, along with Joe Sambrook and Ed Fritsch in 1982. This three-volume manual published by the Cold Spring Harbor Laboratory set a standard for international dissemination of recombinant DNA methods. Dr. Maniatis’ research has led to major advances in understanding the mechanisms of gene expression at the level of RNA transcription and splicing. His current research is focused on the role of single cell diversity in neural connectivity, and on the molecular mechanisms that underlie the neurodegenerative disease ALS (Lou Gehrig’s disease).
Dr. Maniatis’ research contributions have been acknowledged by membership in the U.S. National Academy of Sciences and the Institute of Medicine, and by numerous awards, including, the Eli Lilly Research Award in Microbiology and Immunology, the Novartis Drew Award in Biomedical Research, the Richard Lounsbery Award for Biology and Medicine, and the Lasker Koshland Special Achievement Award in Medical Science. After receiving his BA and MS from the University of Colorado at Boulder and his PhD in molecular biology from Vanderbilt University, Dr. Maniatis carried out postdoctoral studies at Harvard and the Medical Research Council Laboratory of Molecular Biology in Cambridge, England. He has held faculty appointments at Harvard University, the Cold Spring Harbor Laboratory, and the California Institute of Technology.
+David Goldstein, PhD
David Goldstein, PhD, is the John E. Borne Professor of Genetics and Development at Columbia University Medical Center (CUMC), and serves as Director of the Institute for Genomic Medicine, in partnership with NewYork-Presbyterian Hospital. He is an Associate faculty member at NYGC, serving in a senior advisory role for the CGND. Dr. Goldstein also plays a leadership advisory role on planning scientific initiatives at NYGC.
At CUMC and NewYork-Presbyterian Hospital, Dr. Goldstein is building a program that comprehensively integrates genetics and genomics into research, patient care, and education. He is also developing programs to prepare students for careers in the expanding field of genomic and personalized medicine. Dr. Goldstein’s role includes serving as an adviser to Columbia University President Lee C. Bollinger and Executive Vice President for Health and Biomedical Sciences Lee Goldman, MD, on the genetic and genomic components of Columbia’s university-wide initiative in precision or personalized medicine.
Dr. Goldstein was trained in theoretical population genetics, earning his PhD in biological sciences from Stanford in 1994. His research has focused on identifying the relationship between human genetic variations and diseases such as epilepsy, hepatitis C, and schizophrenia, as well as the response of these diseases to pharmacologic treatments.
Previously, Dr. Goldstein was Director of the Center for Human Genome Variation and the Richard and Pat Johnson Distinguished University Professor at Duke University, with appointments in the departments of molecular genetics & microbiology and biology. Prior to joining Duke, Dr. Goldstein was Professor of Genetics at University College London.
A recognized expert in his field, Dr. Goldstein has authored over 200 scholarly publications in the areas of population and medical genetics. He received the Royal Society/Wolfson research merit awards in the UK for work in human population genetics, the Triangle Business Journal Health Care Heroes Award: Innovator/Researcher Award (2008), and the University of North Carolina Clinical Services Award (2012). In 2013, Dr. Goldstein chaired the Gordon Research Conference in Human Genetics & Genomics, and was elected a fellow of the American Association for the Advancement of Science. Dr. Goldstein currently serves on the Advisory Council at NIH’s National Institute of Neurological Disorders and Stroke.
+Dr. Richard Mayeux
Dr. Richard Mayeux is the Gertrude H. Sergievsky Professor of Neurology, Psychiatry and Epidemiology, chair of the Department of Neurology at Columbia University College of Physicians and Surgeons, and Neurologist-in-Chief at NewYork-Presbyterian/Columbia University Medical Center. Dr. Mayeux is also director of the Gertrude H. Sergievsky Center, a center devoted to the epidemiologic investigation of neurological diseases, and co-director of the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Medical Center.
Dr. Mayeux has led a multidisciplinary, population-based investigation of Alzheimer’s disease and related disorders known as the Washington Heights-Inwood Community Aging Project (WHICAP) since 1989. Utilizing this WHICAP population, he and his colleagues were among the first to integrate genetic risk factors and epidemiological principles in an attempt to identify biological markers of susceptibility to degenerative diseases of the aging nervous system. He studies the rates and risk factors for Alzheimer’s disease among elderly of mainly African-American and Caribbean Hispanic descent. Dr. Mayeux also directs a genetic study of Alzheimer’s disease in Caribbean Hispanic families. He has completed two full genome-wide scans in these families and is working to fine map regions of interest. He recently identified genetic variants in the sortilin-related receptor, SORL1, related to Alzheimer’s disease.
Dr. Mayeux is the coordinating investigator for the National Institute on Aging Late Onset Alzheimer’s Disease Family Study. This study began in 2002 with the goal of identifying 1,000 families multiply affected by Alzheimer’s disease. Most recently, he is the lead investigator in a collaborative study of families that display exceptional survival and longevity.
He has been the author of over 350 papers, chapters, and books dealing with various aspects of Alzheimer’s disease and other degenerative diseases of the aging brain. Dr. Mayeux has been the Robert Aird Visiting Professor at the University of California at San Francisco, the Emanuel Goldberg Visiting Professor at the University of Rochester, and the J.L. Silversides Visiting Professor at the University of Toronto. He was the recipient of the Columbia University Dean’s Distinguished Clinical Scientist Award, and received the Rita Hayworth Award from the Alzheimer’s Association.
Dr. Mayeux is a fellow of the American Academy of Neurology and the New York Academy of Science, a member of the American Neurological Association and the Association of American Physicians. He is also a member of the Association for Research in Nervous and Mental Disease, the Society for Epidemiologic Research, and the Society for Neuroscience. He has served as a member of the Aging Review and the Epidemiology of Chronic Disorders Committees for the National Institutes of Health and the Medical and Scientific Advisory Board for the Alzheimer’s Association. In 2001, he was elected to the Institute of Medicine of the National Academies. He has received the 2007 Potamkin Prize from the American Academy of Neurology, the 2008 John Stearns Award for Lifetime Achievement in Medicine from the New York Academy of Medicine, and the 2009 Henry Wisniewski Lifetime Achievement Award in Alzheimer’s Disease Research from the Alzheimer’s Association.
Jan studied biology at the University of Heidelberg in Germany and obtained a M.Sc. by research in life sciences from the University of Edinburgh in Scotland. He joined the laboratory of Prof. William Earnshaw, also at Edinburgh University, where he received his Ph.D. in Cell- and Molecular Biology for his seminal work demonstrating the relationship between local chromatin state, non-coding transcription and the epigenetic inheritance of the centromere locus in mammalian cells. In 2010, Dr. Bergmann moved to New York as postdoctoral fellow in Prof. David Spector’s group at Cold Spring Harbor Laboratory. Here, he spear-headed next-generation sequencing and computational approaches to identify a series of long non-coding RNAs as developmental biomarkers and potential targets for antisense oligonucleotide therapeutics.
Ariel Shepley-McTaggart graduated Columbia University with a BA in May 2014. Ariel splits her time between her life as a professional ballerina and personal trainer to volunteer in our lab several days a week. She works closely with Catherine Braine, investigating the role of TGF-B in a mouse model of ALS. Ariel will attend University of Pennsylvania School of Veterinary Medicine in Fall 2016.
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