The 25th Human Genome Meeting The Next Frontiers in Genomics

Head of the "Akey Lab", located in the Department of Ecology and Evolutionary Biology, at the Lewis-Sigler Institute for Integrative Genomics, Princeton University.

Area of Research: Evolutionary genomics & adaptation.

Prof. Akey's work is guided by the principle that answers to complex and important problems should not be confined by rigid disciplinary boundaries. Thus, he is primarily motivated by important biological questions and uses both experimental, computational, and theoretical methods in our research.

His favorite "model organisms" are yeast, dogs, and humans, each of which is uniquely poised to answer specific questions about the biology and evolution of genomes.

Ami S. Bhatt is an Assistant Professor of Medicine & Genetics, divisions of Hematology and BMT at Stanford University. 

She received her MD and Ph.D. (Biochemistry & Molecular Biology) at UCSF, where she received the Fineberg Award for Excellence in Teaching and was inducted into Alpha Omega Alpha. 

She completed residency and chief residency in Internal Medicine at Brigham & Women’s Hospital and was a fellow in Hematology/Oncology at the Dana-Farber Cancer Institute. Thereafter, she carried out her post-doctoral studies at the Broad Institute of Harvard and MIT.

Ami’s lab seeks to improve outcomes in patients with hematological malignancies by exhaustively characterizing the dynamics of the microbiome in immunocompromised individuals, and exploring how changes in the microbiome are associated with idiopathic diseases in this population. She loves working with trainees and is excited about the application of new molecular and computational technologies to solve complicated metagenomic puzzles. Learning how to organize piles of shotgun metagenomic sequencing data into orderly lists of genomes and genes of potential clinical/biological importance is her passion. 

In addition to her academic efforts, Ami is committed to improving cancer care, education and research in resource-limited settings. She is the Director of Global Oncology for the Center for Innovation in Global Health at Stanford University and has served as a visiting lecturer at the Tokyo Medical and Dental University, Trinity College in Dublin, Ireland and the University of Botswana. She, along with Franklin Huang, is a co-founder and co-president of the non-profit organization Global Oncology (www.globaonc.org). 

• An Associate Professor at the Blavatnik School of Computer Science and the Sackler Faculty of Medicine, Tel Aviv University.
   
• An Affiliate Professor of Genome Sciences at the University of Washington and an External Professor at the Santa Fe Institute.
   
• Principal investigator at the Borenstein Lab for Computational Microbiome Research.

The lab focuses on computational study of the human microbiome and of other complex microbial ecosystems.
Its interest is in the integration of systems biology approaches, computational modeling, data science, and integrative meta-omic analysis to address fundamental questions in microbial ecology and to gain a systems-level, principled, mechanistic understanding of the microbiome.
The lab develops a variety of computational methods and predictive models for studying the human microbiome, and aims to harness such methods for microbiome-based therapy.

Prof. Borenstein's selected awards:

• NIH New Innovator Award
• Alfred P. Sloan Research Fellowship
• Philip Steinmetz Fellowship, Santa Fe Institute
• Yeshaya Horowitz Association Scholarship in Complexity Science
• The Don & Sara Marejn Scholarship
• Best Teacher Award, Tel-Aviv University

Prof. Han Brunner, Academic Researcher for Genetics and Heredity, pursues the scientific understanding of the connections between clinical and molecular features of rare diseases, including applications to patient care.

He has pioneered the discovery of a large number of disease genes and the application of cutting-edge genomic technologies (genomic microarrays, exome sequencing, and whole genome sequencing) to discover the causes of genetic diseases. Much of this work focuses on neurodevelopmental conditions such as intellectual disability and abnormal behavior.

Han Brunner studied medicine at the University of Groningen 1975-1984. He trained as a clinical geneticist at Nijmegen University and was board certified in Clinical Genetics in 1988. In 1998 he was appointed full professor and head of department at the Radboud University Medical Center. As of January 2014 he has a joint appointment in Nijmegen at the department of Human Genetics in Nijmegen and in Maastricht at the department of Clinical Genetics.
 

Honors:

• Han Brunner was elected member of the Royal Netherlands Academy of Arts and Sciences in 2013 and of the Academia Europea in 2012.
• He is a Knight in the Order of the Dutch Lion since 2013.
• He is a co-winner of the King Faisal International Prize in Medicine 2016, with Joris Veltman.
• He is awarded the 2016 Carter medal of the British Clinical Genetics Society.

Principal investgator and head of the"Liran Carmel" Lab, The Alexander Silberman Institute of Life Science at the Hebrew University of Jerusalem. The lab deals with a host of topics in the general fields of molecular evolution and genetics. 

Among the topics that are currently pursued are:

• Human evolution. Recent advances in ancient DNA sequencing yielded genomes (either shotgun sequences with varying degrees of coverage, or SNP arrays) of many ancient anatomically modern humans, as well as of Neanderthals and Denisovans. This open unique opportunities to study the genetic aspects of the very recent lag of our own evolution.
   
• Paleo-epigenetics. the lab developed a technique to reconstruct full DNA methylation maps from high-coverage ancient genomes, and use it to study evolutionary changes in gene regulation, ancient environments and phenotypic adaptations.
   
• Paleo-genetics. the lab studies the genetic structure of ancient populations in Israel.
   
• RNA biology. the lab is studying many aspects of RNA biology, including splicing, nonsense-mediated decay, 3'-end processing, and circular RNAs.
   

Multivariate data analysis. the lab is also active in some fields of applied mathematics: multivariate analysis, statistical pattern recognition, data visualization, and machine learning.

Prizes & Honors
Prof. Carmel's article was selected as the greatest breakthrough of 2019 by the readers of Science magazine

• Chair, Departmental of Cellular and Molecular Medicine.
• Professor of Medicine, Neurosciences, and Cellular and Molecular Medicine.
• Member, Ludwig Institute for Cancer Research.
   

Synopsis of Dr. Cleveland's contribution to Science:YNOPSIS OF D.W. CLEVELAND’S CONTRIBUTIONS TO SCIENCE
Cleveland has made ground-breaking contributions in the regulation of assembly of mitotic spindles and chromosome movement. He discovered the microtubule associated protein tau (mutation in which causes human cognitive disease), the tubulin gene families encoding the major subunits of microtubules, and the first mammalian example of control of gene expression through regulated RNA instability. He identified components required for microtubule nucleation and anchoring during spindle assembly. He discovered CENP-E, the centromere-associated, microtubule-motor that he showed to be a microtubule “tip tracker” essential for powering congression of initially misaligned chromosomes, chromosome attachment at centromeres, and maintenance of  chromosome congression. Using all purified components, he identified that unattached centromeres/kinetochores initiate a two step catalytic cascade signaling mechanism that represents the mitotic checkpoint, the cell cycle control mechanism that prevents errors of chromosome segregation in mitosis. He identified that the meiotic counterpart of the mitotic checkpoint is silenced without development of interkinetochore tension, thereby uncovering a mechanistic basis for the high error frequency of female meiosis in mammals.

 

The centromere is the basic determinant of chromosome inheritance. Unlike genes carried on those chromosomes, however, centromere position is defined by an epigenetic mark, not by DNA sequence. Cleveland identified the basis for epigenetic inheritance of centromere identity. He demonstrated it to be chromatin assembled with the histone H3 variant CENP-A, which he showed to be able to template its own replication through action HJURP, the histone chaperone/chromatin loader he and his team discovered.

 

In neurons cell biology, other major contributions emerged from Cleveland’s demonstration that extreme asymmetry of neurons is achieved with a deformable array of interlinked neurofilaments, microtubules and actin. He showed that disorganization of neurofilaments causes selective failure of motor neurons in mice and humans. He then demonstrated that similar disease could also arise by a toxicity of mutant superoxide dismutase unrelated to its normal activity, thereby uncovering the mechanism underlying a major genetic form of Amyotrophic Lateral Sclerosis (ALS).  He also showed that motor neuron death in inherited ALS is non-cell autonomous, requiring mutant damage to both motor neurons and the neighboring supporting cells. This discovery has wide implications for other major neurodegenerative diseases, since the inherited forms of each are also caused by widely expressed mutant genes. Cleveland’s findings demonstrated the attractiveness of stem cell replacement of non-neuronal cells as a viable therapy in ALS.

 
Synopsis of Dr. Cleveland's contribution to Medicine:
Cleveland has made field leading discoveries into the causes and treatment of ALS and Huntington’s diseases, with implications for a set of additional neurodegenerative/ neuromuscular diseases that include spinal muscular atrophy, myotonic dystrophy and Alzheimer’s and chronic traumatic brain injury. His efforts identified key steps that trigger disease and that accelerate ALS disease progression from mutation in superoxide dismutase. These findings have redirected efforts at stem cell and gene silencing therapies in ALS. Cleveland also identified tau, the microtubule associated protein which misaccumulates in intraneuronal tangles in essentially all instances of Alzheimer’s disease and whose misfolding mediates a slow cell-to-cell spread that is causative of the chronic traumatic encephalopathy associated with repeated brain injury now recognized to be prominent in athletics.

 

Cleveland developed a pair of gene silencing therapies widely applicable in human neurodegenerative disease. His initial approach established utility of “designer DNA drugs” (short single stranded DNAs) that mediate catalytic, RNase H-dependent degradation of the RNA encoded by any selected gene. He demonstrated that single dose infusion of such designer DNA drugs produces durable efficacy (lasting more than three months) throughout the entirety of the rodent and non-human nervous systems. An initial application was for an inherited form of ALS and which entered clinical trial in 2010. In 2013, an extension of this approach entered clinical trial for myotonic dystrophy. Additional trials initiated for Huntington’s disease in 2015 and ALS in 2016, and one is anticipated to initiate early in 2017 for the most frequent cause of ALS and Frontal Temporal Degeneration (FTD), hexanucleotide expansion in the C9orf72 gene.

 

Extensions for development of clinical trials for silencing genes central to Alzheimer’s and Parkinson’s diseases, chronic brain injury, and a set of ataxias are ongoing. An additional application is in trial with a designer DNA drug chemically modified so that it is not recognized by RNase H (and therefore does not stimulate RNA degradation) but acts to correct an RNA splicing abnormality in spinal muscular atrophy, one of the most abundant genetic diseases of children.

 

Cleveland has pioneered additional gene silencing or gene replacement therapies for human nervous system disease using adenoassociated virus (AAV). He and his colleagues have shown remarkably broad delivery within the nervous system and they are now developing this for human clinical trial expected to initiate in 2017 using AAV encoding a short hairpin RNA which acts with the RNA-induced silencing complex (RISC) to trigger degradation of the RNA encoded by a mutated superoxide dismutase gene causative of inherited ALS.

 

Lastly, with his corporate partner Ionis Pharmaceuticals, Cleveland developed the first synthetic CRISPR RNA, demonstrating that it can direct and activate transient, DNA site sequence-specific Cas9 nuclease activity which will cleave and inactivate a target gene. This approach is now in development for therapy combining AAV gene delivery and synthetic CRISPR infusion for gene silencing or correction.

 

Aneuploidy - acquisition of a chromosome content other than a multiple of the haploid number – has long been known to be a frequent component of tumorigenesis. By generating mice that develop aneuploidy at high rates, Cleveland tested the 100 year old hypothesis that aneuploidy drives tumorigenesis. He demonstrated that aneuploidy drives tumorigenesis in some genetic contexts, but suppresses it when combined with tumorigenic mechanisms that independently generate high levels of aneuploidy. Cleveland also discovered the centromere motor CENP-E. His demonstration that inhibition of it induces chronic mitotic arrest followed by cell death for a variety of tumor cells, has enabled development of inhibitors of the CENP-E motor. GlaxoSmithKline and Cytokinetics have taken CENP-E inhibitors to clinical trial for human solid tumors.

 

 

Principal investigator and head of the "ElinavLab", Department of Immunology at the Weizmann Institute of Science.

the ElinavLab members, study the interactions between the mammalian host, its intestinal microbiota, the immune system and their effects on health and disease. They strive to develop human personalized medicine.

Prof. Eran Elinav was awarded the 2018 Mifal HaPais Science Landau Prize in Immunology.

The Leah Omenn Career Development Chair, Principal Investigator and head of the "Ayelet Erez" Lab, Weizmann Institute of Science.

The lab focus is on deciphering the dynamics of cellular metabolism at different disease states. In particular, we are interested in understanding the contribution of the urea cycle enzymes and intermediates to the metabolic changes that accompany disease pathogenesis.
Outside the liver, the urea cycle components serve as metabolic nexus for multiple cellular pathways integrating amino acid/nitrogen and glucose/oxidative stress metabolism. Hence, urea cycle components may directly regulate the differential flux of its metabolites between these pathways.

In addition to basic molecular methods, the lab is using a setup for metabolic characterization which includes GC/MS and specific HPLC instruments for the detection of metabolic changes both in vitro and in vivo.

Awarded a Krill Prize for Excellence in Scientific Research, 2018.

Prof.  Anne Ferguson-Smith is a mammalian developmental geneticist using mouse genetics to explore gene regulation and function.

She is known for her work on genomic imprinting – a process regulated by epigenetic mechanisms - and applying imprinting as a model system to understand epigenetic regulation more widely.

Her work has uncovered epigenetically regulated processes in development and over the life course and identified key in vivo mechanisms involved in the maintenance of epigenetic states. She also explores communication between the environment and the genome with implications for health, disease, and inheritance.
 

Prof.  Anne Ferguson-Smith trained in molecular biology at the University of Glasgow and obtained her Ph.D. in developmental genetics from Yale University. She is the Arthur Balfour Professor of Genetics and Head of the Department of Genetics at the University of Cambridge.

Director, Institute for Health Research and Innovation
Maccabi Healthcare Services.

Prof. Varda Shalev, MD MPH, is the director of the institute of research and innovation Maccabitech (Big-data and Epidemiology research), and an active primary care physician in Maccabi Health Care Services.

With an MD degree from Ben-Gurion University Medical School, she completed her residency in family medicine and earned an MPA in Public Health Administration at Clark University

After a two-year fellowship in medical informatics at the Johns Hopkins University Hospital, Prof. Shalev established the Department of Medical Informatics at Maccabi and was responsible for planning and developing its computerized medical systems.

She has pioneered the development of multiple disease registries to support chronic disease management.
She served as the director of Primary Care division in Maccabi. Shalev’s research interests are in epidemiology, medical informatics and predictive analytics in community healthcare.

She is a member of the European Health Telematics Association and the American Medical Informatics Association.

Prof. Shalev is an Associate Professor at the Tel Aviv University School of Public Health, the teaches Big-data and medical informatics in Tel Aviv University. She has authored or co-authored over 130 publications in peer-reviewed journals

Professor of Medicine (Renal-Electrolyte and Hypertension Division) and Genetics at the Perelman School of Medicine, University of Pennsylvania.

Her laboratory is interested in understanding the pathomechanisms of chronic kidney disease development. Her laboratory uses next-generation sequencing methods and a large collection of human kidney tissue samples to identify novel pathways and biomarkers.

At present, there are more than 1,400 kidney tissue samples in her Biobank. The samples are carefully annotated with functional (eGFR and albuminuria) and structural (glomerulosclerosis and tubulointerstitial fibrosis) parameters. RNAsequencing analysis has been completed for more than 600 microdissected glomerular and tubular samples. These discovery approaches are complemented with careful cell and molecular biological studies to define the role of individual genes and pathways. This analysis identified a concerted dysregulation of immune system, metabolic, and developmental genes (Niranjan et al. Nature Medicine 2008, Kang et al Nature Medicine 2015). While transcript level differences can highlight important changes in human CKD, we believe that integrating these results with genetic and epigenomic studies will be essential to identify causal pathways for CKD development.

As such, her laboratory has been part of the NIH Roadmap Epigenomics Projects to characterize the epigenome of healthy and diseased kidneys. Dr. Susztak has been the recipient of the 2011 Young Investigator Award of the American Society of Nephrology and American Heart Association, one of the most prestigious awards given to researchers under the age of 41 in the field of nephrology. Her laboratory is supported by the National Institute of Health, the American Diabetes Association, the Juvenile Diabetes Research Foundation, and private sources.

"I think this is a really exciting time in science. New technologies are emerging, which will really accelerate research progress, and I think we have fantastic new discoveries ahead of us in biology." 
Prof. Katalin Susztak

Head of Cellular Genetics and Senior Group Leader at the "Wellcome Sanger Institute", UK.

Dr. Teichmann is interested in global principles of protein interactions and gene expression. In particular, her research now focuses on genomics and immunity. From 2016, Sarah is the Head of Cellular Genetics at the Wellcome Sanger Institute.

Sarah did her Ph.D. at the MRC Laboratory of Molecular Biology, Cambridge, UK and was a Beit Memorial Fellow at University College London. She started a group at the MRC Laboratory of Molecular Biology in 2001. In 2013, she moved to the Wellcome Genome Campus in Hinxton, Cambridge, where her group was joint between the EMBL-European Bioinformatics Institute and the Wellcome Sanger Institute.

Sarah is an EMBO member and fellow of the Academy of Medical Sciences, and her work has been recognized by a number of prizes, including the Lister Prize, Biochemical Society Colworth Medal, Royal Society Crick Lecture and EMBO Gold Medal.

Douglas C. Wallace, Ph.D., is Director of the Center for Mitochondrial and Epigenomic Medicine at Children's Hospital of Philadelphia. He holds the Michael and Charles Barnett Endowed Chair in Pediatric Mitochondrial Medicine and Metabolic Diseases.
 

More than 35 years ago, Dr. Wallace and his colleagues founded the field of human mitochondrial genetics. The mitochondria are the cellular power plants, organelles that generate most of the cell’s energy. The mitochondria also contain their own DNA, the mitochondrial DNA (mtDNA), which encodes the wiring diagram for the cell’s power plants. Dr. Wallace showed that the mtDNA is inherited exclusively from the mother and that genetic alterations in the mtDNA can result is a wide range of metabolic and degenerative diseases as well as being important in cancer and aging.

One of his seminal contributions has been to use mtDNA variation to reconstruct the origin and ancient migrations of women. These studies revealed that humans arose in Africa approximately 200,000 years ago, that women left Africa about 65,000 years ago to colonize Eurasia, and from Siberia, they crossed the Bering land bridge to populate the Americas. Studies on the paternally-inherited Y chromosome showed that men went along too.