RNAi-based genetic screening: Past, Present & Future

Organizers

José M. Silva, PhD

Columbia University

Thomas Tuschl, PhD

Rockefeller University

Marta Murcia, PhD

The New York Academy of Sciences

Speakers

Dan Anderson, PhD

Massachusetts Institute of Technology

Dr. Daniel G. Anderson is an Associate Professor in the departments of chemical engineering and the division of health science technology, and is an intramural member of the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. He received his PhD in molecular genetics from the University of California at Davis. At MIT, he pioneered the use of robotic methods for the development of smart biomaterials for drug delivery and tissue engineering. He has developed methods allowing rapid synthesis, formulation, analysis, and biological testing of large libraries of biomaterials for use in medical devices, cell therapy and drug delivery. In particular, the advanced drug delivery systems he has developed provide new methods for nanoparticulate and microparticulate drug delivery, non-viral gene therapy, siRNA delivery, and vaccines. His work has resulted in the publication of over 140 papers, patents and patent applications. These patents have led to a number of licenses to pharmaceutical, chemical and biotechnology companies.

Abraham L. Brass MD, PhD

Massachusetts General Hospital

Abe Brass is an Investigator at the Ragon Institute at Massachusetts General Hospital (MGH) in Boston, Mass. studying viral-host interactions. Abe obtained his M.D. and Ph.D. from the University of Chicago, IL. After a residency in Internal Medicine at the Brigham and Women’s Hospital in Boston Mass., Abe completed his clinical subspecialty training in Gastroenterology at MGH, while working as a postdoctoral research fellow in the Genetics Dept. of Harvard Medical School.

Ramanuj DasGupta, PhD

NYU School of Medicine/Cancer Institute

Dr. DasGupta is Assistant Professor of Pharmacology at the New York University School of Medicine and New York University Cancer Institute. He is also the Director of the RNAi Screening Facility of New York University School of Medicine and member of the Helen and Martin Kimmel Center for Stem Cell Biology, NYUSoM. Trained in Dr. Norbert Perrimon’s lab, Dr. Dasgupta has a unique expertise in state-of-the-art functional genomic approaches, such as RNAi based high-throughput screen in Drosophila and mammalian cultured cells. His lab uses cutting-edge technology to answer basic biological questions in cellular signaling with the specific goal of defining mechanisms of the regulation of the Wnt pathway, both in development and in disease. Recently, Dr. DasGupta has developed an RNAi-based integrated screening technology to identify novel small molecule and microRNA modifiers of the Wnt pathway. The novel and innovative use of combining RNAi with chemical genetics, as well as novel RNAi based enhancer-suppressor screens has allowed his lab to develop very targeted and innovative methods to screen for modifiers of key components of the Wnt signaling pathway. More recently, he has also developed protocols for RNAi-screens aimed at addressing the function of cell-signaling pathways in stem cell maintenance/differentiation in mouse/human embryonic stem cells (ESCs). Since 2006, Dr. DasGupta is the Director of the NYU RNAi screening core facility, which he established within the first few years of arriving at NYU Medical School. As such, he has extensive experience with all facets of siRNA and chemical genomic screening procedures, which he routinely applies to whole genome screens. He also has all of the necessary experience in assay execution, data collection and interpretation along with the requisite reagents, detection equipment, and analysis software for a wide variety of cell-based assays.

Ken Koblan, PhD

Alnylam Pharmaceuticals

Dr. Koblan joined Alnylam in April 2010 with a proven track record of success in the pharmaceutical industry. During his 18 years with Merck Research Laboratories, he held several positions of increasing responsibility culminating in his role as Vice President and site head of Rahway Basic Research. In this role, Dr. Koblan was responsible for leading basic biology and medicinal chemistry research at Merck's largest research center, resulting in two Phase III registration programs, two phase IIb development programs, and the advancement of key pre-clinical drug discovery programs. Dr. Koblan also led the implementation of a significant restructuring initiative that serves as a foundation for sustainable growth within Merck Research Laboratories. Dr. Koblan received his Ph.D. in Biochemistry from Johns Hopkins University and his B.S. in Biology from the Massachusetts Institute of Technology (MIT).

Eva M Hernando-Monge, PhD

NYU Langone Medical-Center

Eva Hernando obtained her PhD degree in Molecular Biology from the University Autonoma (Madrid, Spain) in 1999. She conducted her postdoctoral studies at Memorial Sloan-Kettering Cancer Center and Cold Spring Harbor Laboratories. She became an Assistant Professor at the Department of Pathology of NYU School of Medicine in 2006. Her laboratory studies the molecular basis of sarcoma and melanoma pathogenesis, by analyzing patient samples and using a variety of in vitro and in vivo models.

Craig S. Mickanin, PhD

Novartis Institutes for Biomedical Research

Craig Mickanin obtained his BS degree from the College of William and Mary in 1992. He held positions at the Children’s Hospital of Philadelphia and Onyx Pharmaceuticals prior to joining Novartis Pharamceuticals in 1998. He currently holds the title of Senior Investigator II in the Target Discovery Technologies Unit of the Developmental and Molecular Pathways Department at the Novartis Institutes for Biomedical Research, Inc. in Cambridge, MA. Over the past 10 years, he has pioneered the use of large-scale genome based libraries in the pharmaceutical industy, including the industrialized registration, distribution, and screening of a variety of genome-based sample classes.

Norbert Perrimon, PhD

Harvard Medical School

Dr. Perrimon has 30 years of experience in the fields of developmental genetics, signal transduction and genomics. By developing, improving, and applying a number of genetic techniques (germline clones, FLP/FRT, Gal4/UAS, etc.), his group identified many key components of the Receptor Tyrosine Kinases, JAK/STAT, Wnt, Hedgehog and Notch signaling pathways. In recent years, his group established high-throughout genome-wide RNAi screens to systematically interrogate the entire Drosophila genome in various cell-based assays. In 2003 he created the Drosophila RNAi Screening Center at Harvard Medical School to make this technology available to the community. Currently, his laboratory is applying large-scale RNAi and proteomic methods to obtain a global understanding to the structure of a number of signaling pathways and their cross-talks. In addition, he is studying the roles of signaling pathways in homeostasis and tissue remodeling in Drosophila muscles and gut stem cells. Dr. Perrimon has trained more than 80 students and postdoctoral fellows, with most of them currently holding academic positions.

Jason Rodriguez, PhD

Columbia University

Dr. Jason Rodriguez obtained his Bachelor of Science in Biochemistry from the State University of New York at Geneseo in 1999 and received his doctorate in Biomedicine at Mount Sinai School of Medicine in 2005. His dissertation work discovered how specific paramyxoviruses subvert the Interferon-mediated innate immune system.

Currently, Dr. Jason Rodriguez is a post-doctoral associate in the HHMI laboratory of Dr. Stephen Goff at Columbia University. Dr. Rodriguez’s research focuses on characterizing virus-host interactions of the retroviruses XMRV and HIV. He is actively pursuing whole-genome RNAi technology to identify genes required for HIV infection to gain a better understanding between HIV and its host. Knowledge gained from this work will not only discover key aspects of HIV biology but also a better understanding of host gene function and will open opportunities for therapeutics.

José M. Silva, PhD

Columbia University

Dr. Silva, is an Assistant Professor of Pathology at the Institute for Cancer Genetics, HICCC, at Columbia University Medical Center, New York, since 2008. Dr. Silva’s research centers on breast cancer biology, in particular on the identification of tumor targets for personalized breast cancer therapies. His work focuses on identifying genes that are essential for the viability of breast cancer cells that carry cancer-specific genetic alterations (synthetic lethality) using genome-wide RNAi screens. Blocking the function of these genes will reduce the viability of tumor cells without affecting normal cells, which could lead to more efficient and less harmful breast cancer therapies.

Dr. Silva received a Bachelor of Science degree from the Complutense University of Madrid in 1995, and his doctorate from the Autonoma University of Madrid in 2000. In 2001, he began his postdoctoral studies at Dr. Greg Hannon’s lab at Cold Spring Harbor Laboratory (CHLS), New York, where he was promoted to senior fellow in 2007. During his time at CHSL, Dr. Silva developed shRNA plasmid libraries to target every gene in the human genome and developed a microarray-based platform that facilitates genome-wide RNAi screens.

Serena Silver, PhD

The Broad Institute

Dr. Serena Silver leads the RNAi Screening group within the RNAi Platform at the Broad Institute, where she works with collaborators from the Harvard and MIT community and beyond to design and execute RNAi and overexpression screens.

Dr. Silver and her colleagues have used high throughput RNAi screens to elucidate the pathways and genes important for many developmental processes and disease states, including altered response of an immune cell to pathogens, increased growth of axons from neurons, or increased resistance or susceptibility of a cancer cell to a chemotherapy agent.

Marino Zerial, PhD

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden

Marino Zerial graduated in biology at the University of Trieste in 1982 with a thesis on applied biochemistry of lysosomal storage disorders. He conducted post-doctoral experiences at Institute J. Monod, Paris and at the European Molecular Biology Laboratory EMBL, Heidelberg. He became EMBL Research Group Leader in 1991 when he started his work on the molecular regulation of endocytosis. In 1998 he became Max Planck Director and co-founder of the Max Planck Institute of Molecular Cell Biology and Genetics, MPI-CBG, Dresden. He is honorary Professor at the Medical Faculty, University of Technology, Dresden.
Marino Zerial's research group investigates the molecular mechanisms underlying organelle biogenesis and intracellular transport, focusing on endocytosis, a central process in all eukaryotic cells. His work led to the understanding of the molecular mechanisms underlying endosomal membrane tethering and fusion, especially the role of Rab GTPases in this process, and endosome biogenesis. More recently, he has been combining quantitative image analysis with functional genomics to conduct a system analysis of endocytosis and integrate it with other cellular functions such as signal transduction and cell polarity, in the context of tissue morphogenesis.