Genome Dynamics in Neuroscience and Aging

Lecture

Role of Chromatin and DNA Damage Response Functions in R Loop-Mediated Genome Instability​

Bio

Andrés Aguilera is Professor of Genetics in Seville University and Director of CABIMER. He did his PhD in Seville in 1983 and two postdocts in the Darmstadt Technical University (Germany) and the NYU Medical Center (USA). He started his lab in 1991 focusing his research interests on the mechanisms by which replication, transcription and RNA cause genome instability, in particular those mediated by R loops, and their connection with chromatin modifications, and on the mechanisms of DSB repair by sister chromatid recombination. He is member of EMBO and of international of Boards of different Research Centres and scientific journals.

Lecture

WWOX Mutation, a Newly Discovered Cause for Brain Developmental Disorders​

Bio

Born in Jerusalem, Dr. Rami Aqeilan is a Full Professor of Immunology and Cancer Research at the Hebrew University of Jerusalem. Dr. Aqeilan has had a long-term interest in the genetic and molecular basis of cancer development. Dr. Aqeilan’s laboratory studies the role of fragile genes in cancer development and in neurodegeneration and how defects in DNA double strand breaks impact these maladies. He is the winner of several awards among which is the Sydney Kimmel Award for Cancer Research, Ma’of Fellowship, the Bergman Memorial Research Award, the prestigious ERC-consolidator grant and the 2018-Youdim Prize for Cancer Research.

Lecture

Centenarian: Epigenomic Resilience to Environmental Challenges

Bio

Professor Gil Atzmon is currently an Associate Professor at Albert Einstein College of Medicine, NY, USA and University of Haifa, Israel. A graduate in Population Genetics from the Hebrew University, he completed his fellowship in Human Genetics at Albert Einstein College of Medicine, where he established his lab, parallel to establishing a lab in Haifa. Prof. Atzmon's focus is in a new and challenging field involving the role of genome and epigenome in diseases, aging and longevity.

Lecture

The Role of ATM in Cerebellar Structure and Function​

Lecture

Molecular Mechanisms of Cerebellar Circuit Formation​

Lecture

DNA Damage Signaling to Mitochondrial Dysfunction in Neurodegeneration and Aging​

Bio

Dr. Bohr received his M.D. in 1978, Ph.D. in 1987, and D.Sc. in 1987 from the University of Copenhagen, Denmark. After training in neurology and infectious diseases at the University Hospital in Copenhagen, Dr. Bohr did a postdoctoral fellowship at the University of Copenhagen, Denmark. He then worked at Stanford University as a research scholar from 1982-1986. In 1986 he was appointed to the National Cancer Institute (NCI) as an investigator, becoming a tenured Senior Investigator in 1988. Dr. Bohr developed a research section in DNA repair at the NCI. In 1992 he moved to the NIA to become Chief of the Laboratory of Molecular Genetics. His main contributions have been in the area of DNA repair. He has worked on many aspects of DNA damage and its processing in mammalian cells. He developed a widely used method for the analysis of DNA repair in individual genes and found that active genes are preferentially repaired. This observation was a major advance in the clarification of the tight interaction between DNA repair and transcription, a process termed transcription-coupled repair. In recent years numerous papers from his laboratory have focused on mechanisms of DNA damage processing, particularly on nucleotide excision repair and transcription coupling. A main interest now is to elucidate how these processes change in relation to aging.

Lecture

ADP-ribosylation and Neurological Disease​

Lecture

DNA Damage and Senescence Responses Alter Brain Function​

Bio

Judith Campisi trained in biochemistry and cancer biology at the State University of New York and Harvard Medical School.  She joined the Boston University Medical School faculty, then moved to the Lawrence Berkeley National Laboratory in 1991.  In 2002, she started a second laboratory at the Buck Institute, where she is Professor.  Campisi established a broad program to understand the relationship between aging and disease, with an emphasis on cancer and aging.  She received several awards for her research, is member of the US National Academy of Sciences, and serves on numerous national and international editorial and advisory boards. 

Lecture

Disease Mechanisms in Different Forms of Cerebellar Ataxia​

Bio

Dr. Cathrin Canto is a senior researcher at the Erasmus MC Rotterdam and the Netherlands Institute for Neuroscience (NIN) in Amsterdam, the Netherlands. She is a graduate of the Norwegian University of Science and Technology (NTNU), Kavli Institute for Systems Neuroscience, in Trondheim and the Department of Anatomy and Neurosciences (VU) in Amsterdam. She is interested in unraveling how neuronal firing patterns translate into learning and memory mechanisms. She studies how individuals and groups of cerebellar neurons encode learning and memory during development and aging and the effect of sleep on these processes. In 2015/2016 she received the Distinguished Women in Science award by the Dutch Network of Women Professors.

Lecture

Mitochondrial Metabolic Checkpoint, Stem Cell Aging and Rejuvenation

Bio

Danica Chen is an Associate Professor of Metabolic Biology, Nutritional Sciences & Toxicology at University of California at Berkeley, a member of Berkeley Stem Cell Center, and a member of QB3 Consortium in Lifespan Extension. She was a Searle Scholar, an Ellison Scholar, a Kavli Fellow, and a Hellman Fellow. Dr. Chen received Ph.D. in molecular and cell biology from University of California at Berkeley and obtained postdoctoral training in biology at Massachusetts Institute of Technology. Her research aims to understand the molecular and cellular mechanisms underlying aging-associated conditions and elucidate which aspects of aging-associated conditions are reversible. Recent studies from her lab have revealed mitochondrial stresses as causes of stem cell exhaustion and tissue degeneration during aging. She identified mitochondrial stress resistance programs that become dysregulated in aged stem cells, and demonstrated these programs can be targeted to improve survival and regenerative capacity of aged stem cells. These findings give hope for targeting aging-associated dysregulated cellular protective programs, such as the pathways regulated by NAD+-dependent enzymes sirtuins, to reverse stem cell aging, tissue degeneration and dysfunction. 

Lecture

SIRT6 Promotes Healthy Longevity by Rewiring the Old Metabolome​

Lecture

Bio

Dr Domenico Delia is molecular biologist with a longstanding interest in  ATM kinase and its function in DNA damage responses, and in the neurodegenerative mechanisms occurring in the ATM-deficient the Ataxia Telangiectasia (A-T)  syndrome.

To this aim, he has been developing in vitro model systems of neurodegeneration in A-T using human neural stem cells and more recently neurons and glial cells derived from iPSCs established from patient’s fibroblasts.

Lecture

Defective DNA Repair and Perturbed Autophagy Converge To Promote Neurodegeneration​

Bio

Sherif El-Khamisy is a pharmacist by training, a Wellcome Trust Investigator and a Lister Institute Fellow at the University of Sheffield. Sherif's lab uses a combination of biochemical, genetic and whole animal approaches to study how cells maintain genomic integrity in health and disease. His early work revealed the importance of repairing chromosomal single-strand breaks to maintain neurological function. More recently, the lab identified new players and mechanisms for repairing oxidative and protein-linked chromosomal breaks and uncovered their connection to human disorders such as ataxia, dementia and ALS.

Lecture

DNA Damage and Innate Immune Responses in Development and Disease​

Bio

George A. Garinis is professor of Genetics at the Department of Biology, University of Crete, GR and an affiliated group leader at the Institute of Molecular Biology and Biotechnology (IMBB) in FORTH, Crete, GR. George received his PhD in 2001 from the Medical School of Athens and pursued his postdoctoral studies with Prof. Jan Hoeijmakers (2001-2008) at the Erasmus Medical School in Rotterdam. Using a unique set of DNA repair-deficient mice, his lab has been able to provide us with insights in how persistent DNA damage is functionally linked to the premature onset of metabolic and endocrine perturbations.

Lecture

Unusual RNA/DNA Structures and Genome Stability in Health and Disease

Bio

Natalia is originally from Belarus. She moved to UK to study Molecular Biology at the University of Edinburgh.  She did her PhD in the University of Cambridge, studying regulation of alternative splicing. Natalia did her Post-Doctoral research at the University of Oxford focusing on understanding of co-transcriptional RNA processing events. In 2011, Natalia became a Group Leader at the Dunn School of Pathology, University of Oxford, supported by a Royal Society University Research Fellowship. She is also a fellow of St. John’s College. Natalia investigates the function of usual RNA/DNA structures in health and disease.

Lecture

The Cellular-Molecular Landscape of the Alzheimer’s Brain​

Lecture

Protein Aggregates with Prion-Like Properties in the Aging Vertebrate Brain

Bio

Experimental biology of vertebrate aging and age-related diseases: http://harel-lab.com/

Itamar Harel received his PhD in developmental biology at the Weizmann Institute of Science, and then trained in aging research at Stanford University. In 2018 he joined the Department of Genetics at the Hebrew University as Assistant Professor. To address a major challenge in aging research - the lack of short-lived vertebrate genetic model - he developed a comprehensive genetic platform for rapid exploration of aging and disease in the  African turquoise killifish. This genome-to-phenotype platform includes a sequenced genome, CRISPR/Cas9-based genome editing, and mutant fish for many aging- and disease-relates genes. The Harel lab is exploring fundamental questions in aging biology, such as why is aging such a strong driver of disease? And what is the molecular basis behind the outstanding diversity of vertebrate lifespan (which can reach differences up to 1000-fold).

Lecture

Age and ER Stress Perturb a Neuronal Circuit Which Guards Germline Pluripotency and Fertility in C. elegans

Bio

Dr. Sivan Henis-Korenblit is an associate professor at Bar-Ilan University, Israel.  Her main research interest is identifying the molecular mechanisms of aging using the model organism C. elegans. Her lab investigates abnormal proteostasis stress responses, similar to those that occur as part of the normal aging process, in the context of a whole metazoan, as it ages. Her long-term aim is to develop new ways to overcome age-related proteostasis collapse and improve lifespan and healthspan. Her research combines methodologies of molecular biology, cell biology and genetics to study ER homeostasis and ageing in C. elegans.

Lecture

ATM Deficiency in the Brain and Its Consequences in Microglia and Oligodendrocytes​

Lecture

The Impact of DNA Damage, Transcription Stress and Nutrition on Aging, Protein Aggregation and Neurodegeneration

Bio

Jan Hoeijmakers discovered unexpected DNA rearrangements resolving antigenic variation by which trypanosomes evade immune destruction (PhD thesis). In 1981 he started to study DNA repair (Erasmus Medical Center Rotterdam) and cloned the first human DNA repair gene, followed by many more allowing elucidation of the nucleotide excision repair mechanism and discovery of a surprising link with basal transcription. He clarified the basis of repair disorders, e.g. Cockayne syndrome and trichothiodystrophy. His team generated numerous mouse repair mutants and disclosed a tight connection between DNA damage and (accelerated) aging, a trade-off between cancer and aging and DNA-damage-induced transcription stress in normal aging explaining all proteinopathies. He found that calorie restriction dramatically delays premature aging, most prominently neurodegeneration and triples lifespan in repair-deficient mice by reducing endogenous DNA damage. These findings have wide clinical implications for repair syndromes and dementia’s. For his work he received numerous awards and prizes.

Lecture

Replication Stress Induces Age-Related Disorders via Impaired Mitochondrial Homeostasis

Bio

Lene Juel Rasmussen is Professor at the University of Copenhagen and Managing Director of the interdisciplinary aging center, Center for Healthy Aging, residing within the Faculty of Health and Medical Sciences. Her research aims to unravel the complex molecular basics of aging and the development of aging associated diseases. Within this context, her research group focuses on the molecular understanding of mitochondrial dysfunction and how cells achieve to preserve mitochondrial and nuclear DNA integrity as well as DNA repair.

Lecture

Heterogeneity of Mouse Astrocytes – From Genes to Brain Functions

Bio

Frank Kirchhoff studied biochemistry at the University of Hannover and received a PhD degree in neurobiology from the University of Heidelberg. After research positions in Berlin (MDC) and Göttingen (MPI Experimental Medicine), he is now full professor of physiology at the Center for Integrative Physiology and Molecular Medicine (University of Saarland, Homburg). His research focuses on the molecular and cellular mechanisms of neuron-glia interaction in the central nervous system (CNS). Employing in vivo two-photon imaging and genetically modified mice, his group studies, in particular, the functional role of transmitter receptors in astrocytes and oligodendrocytes of various CNS regions.

Lecture

Accumulation of Senescent Cells – Mechanisms and Consequences

Bio

Cellular senescence in aging, tissue damage, cancer and embryonic development. Web: http://www.weizmann.ac.il/mcb/valery/

Dr. Krizhanovsky received his PhD in Biology at the Hebrew University of Jerusalem in 2005.  He then did his postdoctoral training at Cold Spring Harbor Laboratory, USA. In 2010 Dr. Krizhanovsky joined Weizmann Institute of Science where he is now Associate Professor at the Department of Molecular Cell Biology. During his carrier, he discovered the role of cellular senescence in tissue damage, established the role of NK cells in the immune surveillance of senescent cells, presence of senescence in the placenta and discovered senolytic pathways allowing specific elimination of senescent cells in vivo. His laboratory studies the role of senescent cells in aging, age-related diseases and cancer.  

Lecture

Processing of Physiologically–Induced DNA DSB is Defective in Purkinje Cells in a Mouse Model of the Human Genetic Disorder Ataxia-Telangiectasia​

Bio

Martin Lavin is Foundation Professor of Molecular Oncology at the University of Queensland. He obtained his PhD at Trinity College Dublin before taking up appointments at the University of Queensland and the Queensland Institute of Medical Research.The main focus of his research is on rare genetic disorders characterized by defects in the DNA damage response  including ataxia-telangiectasia (A-T). He has investigated the genetic and biochemical basis of A-T for many years with emphasis on the function of ATM, the protein defective in A-T employing model systems to investigate the neurodegenerative phenotype and extending these studies to a more translational level.  

Lecture

Genome Maintenance and Nervous System Function

Bio

Peter McKinnon received his PhD from Adelaide, Australia where he worked on chromatin structure and ataxia telangiectasia (A-T), subsequently developing an interest in the neurobiology of A-T.  His postdoctoral focused on molecular neurobiology and mouse genetics.  Upon moving to St. Jude Children’s Hospital as a faculty member, he established a research program to study the neurobiology of A-T.  This work broadened to examine the relationship between DNA damage signaling, genome instability and disease in the nervous system.

Lecture

Region-Specific Pathogenic Transcriptome Profiles – Towards Understanding Regional Variation in SCA1 Pathogenesis

Bio

Orr completed his Ph.D. at Washington University, a Postdoctoral fellowship at Harvard, and joined the University of Minnesota faculty in 1981.  His research uses genetic, biochemical, and behavioral approaches to study the polyQ neurodegenerative disease spinocerebellar ataxia type 1 (SCA1). In collaboration with Huda Zoghbi at Baylor, the gene affected in SCA1 - the first genetically defined ataxia – was cloned in 1993. They established the first transgenic mouse model of a polyglutamine disease. The work indicates that the normal function(s) of Ataxin-1 are critical for disease. Use of RNA-seq to identify pathways involved in SCA1 is underway. Current focus is on two signaling pathways each having distinct but seminal roles in SCA1, phosphorylation of ATXN1 at Ser776 and activation of Cck1Rs to dampened Purkinje cell degeneration in SCA1 and other SCAs.

Lecture

ATM and Regulation of Protein Homeostasis in Human Cells​

Bio

Dr. Paull received her B.S. and M.S. in Biological Sciences from Stanford Univ. in 1991, and received her Ph.D. from UCLA in 1996. Her post-doctoral research with Dr. Martin Gellert at NIH was supported by a fellowship from the Helen Hay Whitney Foundation. Dr. Paull established an independent laboratory in 2000 in the Dept. of Molecular Genetics and Microbiology at the University of Texas at Austin. Her research is aimed toward understanding the DNA damage response in eukaryotic cells, as well as the intersection between this response, oxidative stress signaling, and protein homeostasis.

Lecture

Cellular Roles of the CDKL5 Kinase Relevant To CDKL5 Disorder​

Bio

John Rouse’s research focuses on the molecular mechanisms underlying the signalling and repair of DNA damage. His team’s work places strong emphasis on how DNA repair mechanisms are controlled by protein phosphorylation and ubiquitylation. A major aim of John’s work is to understand how derailment of DNA repair can cause disease, and to understand how pathogenic mutations affect DNA repair. Over the years John’s laboratory has discovered a host of factors vital for DNA repair. These include the SLX4 regulator of DNA repair nucleases, the FAN1 DNA repair nuclease and the DVC1/SPRTN protease all of which play critical roles in preventing genome instability and disease.

Lecture

Systemic DNA Damage Responses in Aging and Disease

Bio

Björn Schumacher directs the Institute for Genome Stability in Ageing and Diseases at CECAD Research Centre of the University of Cologne. He conducted his PhD at the Max Planck Institute for Biochemistry in Munich and postdoctoral research at the Erasmus Medical Centre in Rotterdam. B.S. is President of the German Society for Ageing Research and Vice President of the German Society for DNA Repair. His research interest focuses on the causal role of DNA damage in cancer and ageing-associated diseases. His group uncovered cell-autonomous and systemic responses through which the organism adapts to accumulating DNA damage during ageing.

Lecture

Ataxia-telangiectasia: Are We Closer to Understanding the Ataxia?​

Bio

Dr. Yosef Shiloh is Myers Professor of Cancer Genetics and a Research Professor of the Israel Cancer Research Fund, at the Sackler School of Medicine, Tel Aviv University. He obtained his Ph.D. in Human Genetics at The Hebrew University of Jerusalem. He trained further at Harvard Medical School, the University of Michigan, New York University Cancer Center and Memorial Sloan Kettering Cancer Center in New York, and was a Fogarty Fellow at the U.S. National Institutes of Health. He has dedicated most of his scientific career to understanding the genome instability syndrome, ataxia-telangiectasia (A-T). ​

Lecture

The Role of SIRT6 in DNA Damage and Neurodegeneration

Bio

Debbie Toiber works on models of ageing and neurodegeneration involved in genomic stability. Debbie did her PhD in Prof. Soreq’s lab at the Hebrew University of Jerusalem, where she discovered novel variants of AChE and their roles in brain pathology. During her Postdoctoral studies at Prof. Mostoslavsky lab in MGH-Harvard Medical School, Debbie studies the role of SIRT6 response to double-strand breaks. She is in Ben Gurion University in Israel since 2014, where she studies the role of SIRT6 in preventing DNA damage accumulation, and premature brain aging. 

Lecture

Genome Dynamics in the Brain-Gut Axis​

Lecture

Single-Cell, Integrated Analysis of Genome Instability in Aging

Bio

Jan Vijg, Ph.D., is Professor and Chairman of the Department of Genetics at the Albert Einstein College of Medicine in New York since July, 2008. He received his Ph.D. at the University of Leiden, The Netherlands, in 1987. From 1990 to 1993 he was founder and Scientific Director of Ingeny B.V., a Dutch Biotechnology company. In 1993 he moved to Boston, to take up a position as Associate Professor of Medicine at Harvard Medical School. In 1998 he accepted an offer from the University of Texas Health Science Center in San Antonio, Texas, to become a Professor in the Department of Physiology. From 2006 to 2008 he was a Professor at the Buck Institute for Age Research in Novato, California. With his research team he was the first to develop transgenic mouse models for studying mutagenesis in vivo (in 1989) and has used these models ever since in studying the relationship between damage to the genome and aging. He has published over 300 scientific articles and three books, and is inventor or co-inventor on 8 patents.

Lecture

DNA Damage Response in Neuronal Homeostasis

Bio

Dr Zhao-Qi Wang received his B.S. from Shandong University in 1982; M.S. from Peking Union Medical College (PUMC) in 1985; Ph.D. from Innsbruck University in 1993. From 1988-1997 he was Postdoctoral fellow, Staff Scientist and Scientist at Institute of Molecular Pathology (I.M.P.) Vienna. 1997-2006 he was Unit Chief at International Agency for Research on Cancer (IARC) Lyon; Since 2006 he is a full Professor at Friedrich-Schiller-University Jena and Senior Group Leader at Leibniz Institute on Aging—Fritz Lipmann Institute (FLI), Jena, Germany. His research focuses on DNA damage response and genomic stability using mouse models. His favorite molecules include ATM, ATR, NBS1, PARP1, MCPH1 and Trrap-HAT.