Genome Integrity Discussion Group December 2016

Organizers

Scott Keeney, PhD

Memorial Sloan Kettering Cancer Center

Susan Smith, PhD

NYU Langone Medical Center

Lorraine Symington, PhD

Columbia University Irving Medical Center

Sonya Dougal, PhD

The New York Academy of Sciences

Caitlin McOmish, PhD

The New York Academy of Sciences

Speakers

Songtao Jia, PhD

Columbia University

Dr. Songtao Jia obtained his Bachelor's degree in Molecular Biology from Nankai Univeristy, China. He obtained his PhD degree in Biochemistry from UCLA, working with Dr. Albert Courey to study the mechanism of transcriptional regulation during early embryo development. He did his postdoctoral research in the laboratory of Dr. Shiv Grewal, first at Cold Spring Harbor laboratory and then at the National Cancer Institute, to study the role of non-coding RNAs in the regulation of higher order chromatin assembly. Dr. Jia established his own lab at Columbia University in 2006 and is currently an Associate Professor at the Department of Biological Sciences. His lab studies epigenetics: the regulation of chromatin structure to control the accessibility of genetic information. Epigenetic mechanisms gradually restrict the developmental potential of stem cells during differentiation and also constitute memories of gene activity, which ensure faithful inheritance of cell identity. Defects in epigenetic regulation have been extensively demonstrated to play causal roles in numerous developmental disorders and cancers. Dr. Jia's lab uses a combination of approaches, such as high throughput genetic screens, genomics, and proteomics, combined with traditional genetic and biochemical analyses to study the role of epigenetic mechanisms in regulating genome function in fission yeast. His lab has also developed yeast models of human diseases, taking advantage of the power of yeast genetics to identify the underlying molecular mechanisms of these diseases.

Luciano Marraffini, PhD

The Rockefeller University

Dr. Marraffini received his undergraduate degree from the University of Rosario in Argentina in 1998 and his Ph.D. from the University of Chicago in 2007, studying bacterial pathogenesis in the laboratory of Dr. Olaf Schneewind. He was a postdoc at Northwestern University from 2008 to 2010 with Dr. Erik Sontheimer, where he pioneered studies on CRISPR-Cas immunity. Dr. Marraffini determined that that CRISPR-Cas systems target DNA molecules in a sequence-specific manner, a study that was key to understand the mechanisms of CRISPR immunity at the molecular level. This finding also predicted the existence of RNA-programmable Cas nucleases and their applications. In 2010 he joined Rockefeller University as assistant professor. He is a 2012 Rita Allen Foundation Scholar and a 2011 Searle Scholar and is the recipient of a 2012 NIH Director’s New Innovator Award, a 2015 Burroughs Wellcome Fund PATH Award and the 2016 ASBMB Earl and Thressa Stadtman Distinguished Scientist Award. For more information about Dr. Marraffini please visit http://marraffini.rockefeller.edu.

Alexandra L. Nuygen

Rutgers

Alexandra Nguyen is a PhD student in Cell and Developmental Biology at Rutgers University working under the guidance of Dr. Karen Schindler. Dr. Schindler's lab focuses on the processes that control female gamete formation in mice. Alexandra received her Bachelor's degree in Biology from the University of North Florida with an emphasis in Ecology and Evolutionary biology. Her undergraduate research focused on the reproductive health of a large land tortoise species called the Gopher Tortoise. After graduation Alexandra was interested in learning molecular techniques to study reproduction so she joined the Schindler lab first as a technician. As a technician Alexandra was involved in determining a role for Haspin in regulating Aurora Kinase C in female meiosis. Through this work she became interested in deepening her understanding about the molecular mechanisms that control meiosis I in mouse oocytes and will present data from her PhD thesis work here where she is elucidating the requirements for the Aurora protein kinases during female meiosis.

Ehsan Pourkarimi, PhD

Memorial Sloan-Kettering

Ehsan Pourkarimi did his undergraduate studies in Budapest, Hungary. During this time, he uncovered the role of anti-metastasis gene, nm23 in modulating the level of Ras/MAPK signaling and also demonstrated the role of nm23 in mediating cell migration and apoptosis engulfment. After receiving a Cancer Research UK fellowship, he moved to Welcome Trust center for Gene Regulation and Expression in United Kingdom and undertook his PhD in Anton Gartner's lab. During his PhD he characterized the key components of C. elegans core apoptotic machinery and challenged the well accepted model of apoptosis induction in C. elegans. He also optimized and developed SILAC/quantitative proteomics approach in C. elegans and studied the effect of acute stress response in an organismal level. His research led to the discovery of the role of histone H3.3 variants in both starvation response and aging. For his post-doctoral research, Ehsan was interested to study replication initiation. Therefore, he joined Dr. Iestyn Whithouse's lab, at MSKCC in New York where he has introduced and stablished C. elegans research in the lab and has shifted his research interest to study DNA replication and its relation to chromatin modifications.

Bruce Stillman, PhD

Cold Spring Harbor Laboratory

Dr. Bruce Stillman is President & CEO of Cold Spring Harbor Laboratory. A native of Australia, he graduated with a Bachelor of Science degree with first class honors at The University of Sydney and a Ph.D. at the John Curtin School of Medical Research at the Australian National University. He moved to CSHL as a Postdoctoral Fellow in 1979 and has been at the Laboratory ever since. Dr. Stillman has been Director of the CSHL Cancer Center since 1992. In 1994, he succeeded Nobel laureate James D. Watson as Director of Cold Spring Harbor Laboratory and was appointed President in 2003.

Dr. Stillman's research focuses on the mechanism and regulation of duplication of DNA and chromatin in cells. He has been elected to The Royal Society (UK), the National Academy of Sciences, the Australian Academy of Sciences and the American Academy of Arts and Sciences. Dr. Stillman received a number of awards and prizes, including the Alfred P. Sloan Prize from the General Motors Cancer Research Foundation, the Louisa Gross Horwitz Prize from Columbia University, and the Herbert Tabor Research Award from The American Society for Biochemistry and Molecular Biology (ASBMS). He is an advisor to universities, foundations, corporations and government agencies.

Jingsong Yuan, MD, PhD

Columbia University Irving Medical Center

Dr. Jingsong Yuan's research goal is to leverage his expertise in the field of DNA damage repair for translation into the realm of cancer biology and therapeutics. Dr. Yuan's main interest is in the underlying molecular mechanisms that result in genomic instability and tumorigenesis, specifically, in understanding the molecular mechanisms underlying DNA replication stress response and homologous recombination (HR) DNA repair, the function of which is critical for preventing genomic instability and tumorigenesis. Dr. Yuan and his colleagues identified the roles of two annealing helicases, HARP/SMARCAL1 and AH2/ZRANB3, in stabilizing stalled replication forks, facilitating DNA repair and maintaining genome stability in response to replication stress. He showed that DNA double-strand breaks (DSBs)-induced DNA damage signaling cascade and HR-mediated DSB repair pathway can be genetically separated. He reported that the MRN (MRE11-RAD50-NBS1) complex is responsible for initial recognition of DSBs, it then works together with CtIP, a binding partner of BRCA1, and the H2AX-dependent DNA damage-signaling cascade to facilitate HR repair and DNA damage checkpoint activation. Dr. Yuan uncovered human SWI5-MEI5 complex and FIGNL1 complex, and showed that they have an evolutionarily conserved function in HR repair. Most recently, Dr. Yuan's group identified ETAA1 (Ewing tumor-associated antigen 1), also known as ETAA16, as a novel ATR activator involved in replication and DNA damage checkpoint control, and therefore provided a plausible explanation for why variants at ETAA1 loci increase the risk of developing cancer.