KEYNOTE SPEAKERS


Links within this page:  
     
DREAM
CHALLENGES
SYSTEMS IMMUNOLOGY
SPECIAL SESSION
REGULATORY GENOMICS
& SYSTEMS BIOLOGY

- Joel Dudley
- Nir Hacohen - Jef Boeke
- Henry Rodriguez - Dana Pe'er - Mannolis Kellis
  - Jedd Wolchok - Erez Lieberman-Aidan
    - Debora Marks
    - Laxmi Parida











DREAM CHALLENGES

Joel Dudley, PhD
Director, Next Generation Healthcare Institute
Associate Professor, Genetics and Genomic Sciences; Population Health Science and Policy; Medicine
Icahn School of Medicine at Mount Sinai
New York, USA

> Click here for biography <

Title and abstract: please check back for updates

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Henry Rodriguez, PhD, MS, MBA
Director
Office of Cancer Clinical Proteomics Research
Office of the Director, National Cancer Institute, NIH
Maryland, USA

> Click here for biography <

Omics Convergence (Proteogenomics) in Cancer Research: Advances in Precision Medicine

Despite significant progress in understanding cancer through massively parallel sequencing genome programs, the complexity that comprises its diseases remains a daunting barrier.  Today we know that molecular drivers of cancer are derived not just from DNA alterations alone, but from protein expression and activity at the cellular pathway level - proteomics.  To predict the downstream effects of gene alterations, orthogonal technologies such as next-generation proteomics are needed.  This proteogenomics approach is anticipated to transform oncology care from one that relies mainly on trial-and-error treatment strategies based on the anatomy of the tumor, to one that is more precisely based on the tumor’s molecular profile.  This seminar will discuss how genomics, transcriptomics, and proteomics must be brought together in the quest to understand the etiology of cancer, in addition to highlighting efforts by the U.S. National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) program in this area of biomedical research.  CPTAC’s proteogenomics approach was recently successful in demonstrating the scientific benefits of integrating proteomics with genomics to produce a more unified understanding of cancer biology and possibly therapeutic interventions for patients, while creating open community resources that are widely used by the global cancer community.  This seminar will also highlight the recently announced Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) program and the International Cancer Proteogenomic Consortium (ICPC), launched in 2016 in coordination with the Beau Biden Cancer Moonshot effort.

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SYSTEMS IMMUNOLOGY SPECIAL SESSION

Nir Hacohen, PhD
Massachusetts General Hospital
Director, MGH Center for Cancer Immunotherapy
Center for Cancer Research
Massachusetts, USA

Biography, title, and abstract: please check back for updates

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Dana Pe'er, PhD
Chair
Computational and Systems Biology Program
Memorial Sloan Kettering Cancer Center
New York, USA

Biography, title, and abstract: please check back for updates


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Jedd D. Wolchok, MD, PhD
Lloyd J. Old/Virginia and Daniel K. Ludwig Chair in Clinical Investigation
Chief, Melanoma & Immunotherapeutics Service
Director, Parker Institute for Cancer Immunotherapy at MSK
Associate Director, Ludwig Center for Cancer Immunotherapy
Member, Ludwig Cancer Research
Professor of Medicine, Weill Medical College of Cornell University
Memorial Sloan Kettering Cancer Center

New York, USA

 > Click here for biography <

Immunologic Checkpoint Blockade: Exploring Combinations and Mechanisms

Given the activity noted with both CTLA-4 or PD-1 blockade, clinical trials are now investigating combination checkpoint blockade. The most mature data with a combination of ipilimumab + nivolumab in melanoma showed a response rate of 60% in the context of increased, yet manageable toxicity. Such responses are generally durable, even when treatment was stopped early for toxicity. Unlike in studies of PD-1 blockade monotherapy, there was no significant difference in clinical activity based on tumor expression of PD-L1. This approach has gained regulatory approval for metastatic melanoma and is in late stage clinical trials for other malignancies. Attention is being paid to the reasons underlying the efficacy of checkpoint blockade in certain malignancies. One hypothesis has been that cancers having a high mutational load may be more amenable to immune modulation by virtue of the larger number of potential neo-epitopes present, fostering baseline immune recognition that can then be potentiated by checkpoint blockade. We have found that melanoma patients having long term clinical activity with ipilimumab have a significantly greater median number of non-synonymous passenger mutations, compared with patients who do not respond or those who have only short-term regression. Strategies to enhance baseline immune reactivity are therefore necessary to investigate as means to improve the impact of checkpoint blockade on a broad spectrum of cancers. The presence of suppressive myeloid cells in the tumor microenvironment also is emerging as a mechanism of resistance to the anti-tumor activity for checkpoint blockade. Strategies to overcome this include inhibition of CSF-1R signaling, IDO activity and selective suppression of PI3K-y
.

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REGULATORY GENOMICS & SYSTEMS BIOLOGY

Jef Boeke, PhD

Professor, Department of Biochemistry and Molecular Pharmacology
Director, Institute for Systems Genetics
NYU School of Medicine
New York, USA

Biography, title, and abstract: please check back for updates

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Manolis Kellis, PhD
Institute Member, Broad Institute of MIT and Harvard
Professor of Computer Science
Principal Investigator, Computer Science and Artificial Intelligence Laboratory
Massachusetts, USA


> Click here for biography <

Title and abstract: please check back for updates

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Erez Lieberman-Aiden, PhD
Assistant Professor
Baylor College of Medicine & Rice University

Texas, USA

> Click here for biography <

A 3D Code in the Human Genome


Stretched out from end-to-end, the human genome – a sequence of 3 billion chemical letters inscribed in a molecule called DNA – is over 2 meters long. Famously, short stretches of DNA fold into a double helix, which wind around histone proteins to form the 10nm fiber. But what about longer pieces? Does the genome’s fold influence function? How does the information contained in such an ultra-dense packing even remain accessible?

In this talk, I describe our work developing ‘Hi-C’ (Lieberman-Aiden et al., Science, 2009; Aiden, Science, 2011) and more recently ‘in-situ Hi-C’ (Rao & Huntley et al., Cell, 2014), which use proximity ligation to transform pairs of physically adjacent DNA loci into chimeric DNA sequences. Sequencing a library of such chimeras makes it possible to create genome-wide maps of physical contacts between pairs of loci, revealing features of genome folding in 3D.

Next, I will describe recent work using in situ Hi-C to construct haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ∼10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind the protein CTCF. The CTCF motifs at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs “facing” one another.

Next, I will discuss the biophysical mechanism that underlies chromatin looping. Specifically, our data is consistent with the formation of loops by extrusion (Sanborn & Rao et al., PNAS, 2015). In fact, in many cases, the local structure of Hi-C maps may be predicted in silico based on patterns of CTCF binding and an extrusion-based model.

Finally, I will show that by modifying CTCF motifs using CRISPR, we can reliably add, move, and delete loops and domains. Thus, it possible not only to “read” the genome’s 3D architecture, but also to write it.

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Debora Marks, PhD
Assistant Professor of Systems Biology
Harvard Medical School
Massachusetts, USA

Biography, title, and abstract: please check back for updates


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Laxmi Parida, PhD
Distinguished RSM & Manager, Computational Genomics Group
Thomas J. Watson Research Center
IBM Research
New York, USA

> Click here for biography <


Title and abstract: please check back for updates

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BIOGRAPHIES (in alphabetical order)

Joel Dudley, PhD
Dr. Dudley is a recognized leader in applying biomedical Big Data to healthcare and drug discovery. He currently holds positions as Associate Professor of Genetics and Genomic Sciences and Director of Biomedical Informatics at the Icahn School of Medicine at Mount Sinai. He also directs the newly formed Institute for Next Generation Healthcare at Mount Sinai. Prior to Mount Sinai, he held positions as Co-founder and Director of Informatics at NuMedii, Inc., one of the first companies to apply Big Data to drug discovery, and Consulting Professor of Systems Medicine in the Department of Pediatrics at Stanford University School of Medicine. His work is focused on developing and applying advanced computational methods to integrate the digital universe of information to build better predictive models of disease, drug response. He and his team are also developing pioneering methods to bring about a next generation of medicine that leverages advances in diagnostics, wearables, digital health to enable new approaches to precision medicine and scientific wellness. He has authored and co-authored more than 80 publications and his research has been featured in the Wall Street Journal, Scientific American, Forbes, and other popular media outlets. His recent work using a Big Data approach to identify subtypes of Type 2 diabetes was recently highlighted by NIH director Francis Collins on the the NIH Director’s Blog as a significant advance in precision medicine. He was named in 2014 as one of the 100 most creative people in business by Fast Company magazine. He is coauthor of the book Exploring Personal Genomics from Oxford University Press, which is used as a text in personalized and precision medicine courses at universities worldwide. He holds an MS and PhD in Biomedical Informatics from Stanford University School of Medicine. Dr. Dudley serves on the Scientific Advisory boards of numerous startups and companies in biotech and healthtech.

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Manolis Kellis, PhD
Manolis Kellis is an institute member at the Broad Institute and a professor of computer science at MIT, where he is a principal investigator in the Computer Science and Artificial Intelligence Laboratory. He has led or co-led several large-scale efforts in comparative and integrative genomics and epigenomics. His group leads the integrative analysis efforts of the ENCODE, modENCODE, and National Institutes of Health Roadmap Epigenomics projects.

Kellis and his group have developed methods for systematically interpreting the human genome and the molecular basis of human disease by computational integration of large-scale functional and comparative genomics datasets. Kellis has defined evolutionary, chromatin, and activity signatures, combining them to elucidate the function and regulatory circuitry of the human genome to gain new insights into human biology. His team has also leveraged this information to interpret variants linked to several diseases and phenotypes from genome-wide association studies.

Prior to computational biology, Kellis worked on artificial intelligence, sketch and image recognition, robotics, and computational geometry at MIT and PARC, a Xerox company commonly referred to as the Palo Alto Research Center.

Kellis has received the Presidential Early Career Awards for Scientists and Engineers, the highest honor bestowed by the United States government on science and engineering professionals in the early stages of their independent research careers. He has also received the National Science Foundation CAREER award, the Alfred P. Sloan Foundation’s Sloan Research Fellowship, the Niki Award from the Athens Information Technology Center of Excellence for Research and Education, the MIT Technology Review’s TR35 honor for scientists and researchers under age 35, the Ruth and Joel Spira Teaching Award for excellence in teaching, and the MIT Sprowls Award for the best Ph.D. thesis in computer science.

He obtained his B.S., M.Eng., and Ph.D. from MIT.

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Erez Lieberman-Aiden, PhD
Erez Lieberman Aiden received his PhD from Harvard and MIT in 2010. After several years at Harvard's Society of Fellows and at Google as Visiting Faculty, he became Assistant Professor of Genetics at Baylor College of Medicine and of Computer Science and Applied Mathematics at Rice University.

Dr. Aiden's inventions include the Hi-C method for three-dimensional DNA sequencing, which enables scientists to examine how the two-meter long human genome folds up inside the tiny space of the cell nucleus (Lieberman-Aiden & Van Berkum et al., Science, 2009). In 2014, his laboratory reported the first comprehensive map of loops across the human genome, mapping their anchors with single-base-pair resolution (Rao & Huntley et al., Cell, 2014). In 2015, his lab showed that these loops form by extrusion, and that it is possible to add and remove loops and domains in a predictable fashion using targeted mutations as short as a single base pair (Sanborn & Rao et al., PNAS, 2014). In 2017, his lab showed that it is possible to use 3D maps, generated using Hi-C, to assemble mammalian genomes, entirely from scratch, from short reads alone, at a total cost of under $10,000 (Dudchenko et al., Cell, 2014). Using this methodology, the Aiden lab reported the first end-to-end genome of the Aedes aegypti genome, which carries the Zika virus. Assembling the Aedes aegypti genome from end-to-end had been highlighted as essential to the worldwide Zika response by a front page article in the New York Times.

In addition, together with Jean-Baptiste Michel, Dr. Aiden also developed the Google Ngram Viewer, a tool for probing cultural change by exploring the frequency of words and phrases in books over the centuries. Now a product at Google, the Ngram Viewer is used every day by millions of people worldwide.

Dr. Aiden's research has won numerous awards, including recognition for one of the top 20 "Biotech Breakthroughs that will Change Medicine", by Popular Mechanics, membership in Technology Review's 2009 TR35, recognizing the top 35 innovators under 35; and in Cell's 2014 40 Under 40. His work has been featured on the front page of the New York Times, the Boston Globe, the Wall Street Journal, and the Houston Chronicle. One of his talks has been viewed over 1 million times at TED.com. Three of his research papers have appeared on the cover of Nature and Science. In 2012, he received the President's Early Career Award in Science and Engineering, the highest government honor for young scientists, from Barack Obama. In 2014, Fast Company called him "America's brightest young academic." In 2015, his laboratory was recognized on the floor of the US House of Representatives for its discoveries about the structure of DNA.

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Laxmi Parida, PhD
Computational genomics, Pattern Discovery, Design and Analysis of Algorithms, Population Genomics, Comparative Genomics, NGS Analysis, Bioinformatics, Cancer Genomics, Topological Data Analysis.

Currently leading the science team in the personalized cancer medicine system, Watson for Genomics. and the Sequence the Food Supply Chain Consortium. Laxmi also led the IBM Science team in the Cacao Consortium with MARS and USDA and continue to work on plant genomics. Additionally, she led the Reco project/Genographic Project with National Geographic and continue to work on population genomics.

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Henry Rodriguez, PhD, MS, MBA
Dr. Rodriguez is Director of the Office of Cancer Clinical Proteomics Research at the National Cancer Institute (NCI), National Institutes of Health (NIH). Prior to the NCI, he was Director of the Cell & Tissue Measurements Group, Director of the Tissue Engineering program, Principal Scientist in the DNA Damage and Repair program, and Program Analyst (Office of the Director), at the National Institute of Standards and Technology. Dr. Rodriguez’s research has focused on understanding mechanisms of cancer and age-related diseases, including the development of molecular-based technologies in basic, translational, and clinical science.

Dr. Rodriguez has led the development of NCI’s clinical proteomic and proteogenomic research programs, which today includes the world’s largest public repository of proteogenomic sequence data and targeted fit-for-purpose assays. These efforts led to the formation of two Beau Biden Cancer MoonshotSM initiatives – the International Cancer Proteogenome Consortium (ICPC) and the Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) network, of which he developed and co-developed. Dr. Rodriguez’s honors include Presidential Citation, American Association for Clinical Chemistry; NIH Director's Award, National Institutes of Health; NCI Director’s Award, National Cancer Institute, NIH; Wertheim Global Medical Leadership Award, Herbert Wertheim College of Medicine at Florida International University; and Leveraging Collaboration Award, U.S. Food and Drug Administration. He has authored more than 121 peer-reviewed original research papers, including co-editing a best-selling book on oxidative stress and aging. Dr. Rodriguez received his B.S. in biology/chemistry and M.S. in biology/toxicology from Florida International University, Ph.D. in cell and molecular biology from Boston University, and M.B.A. in finance and management from Johns Hopkins University Carey Business School. Research fellowships were conducted at The Scripps Research Institute (Department of Immunology) and at City of Hope National Medical Center (Department of Medical Oncology).

For more information, please visit: https://proteomics.cancer.gov/about/staff/henry-rodriguez-phd-ms-mba

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Jedd D. Wolchok, MD, PhD
Dr. Wolchok is chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center (MSK). His insight and innovation have placed him at the leading edge of cancer immunotherapy in two different roles:  An active clinician-scientist exploring innovative immunotherapeutic strategies in laboratory models, and a principal investigator in numerous pivotal clinical trials. His specific research interest is the pre-clinical and early clinical development of novel immunologic therapies. Most recently, Dr. Wolchok has initiated several clinical trials using plasmid DNA vaccines for patients with melanoma. He’s been involved in the development of the DNA vaccine program at every level – from initial studies in mouse models, through all levels of regulatory review, and now as principal investigator of the clinical trials.


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