Current News
UNC Mouse Resource highlighted in special issue of Genetics/G3 featuring 11 papers coauthored by CCGS faculty
February 24, 2012
The February 2012 issue of the GENETICS and G3 journals featured 15 articles featuring the Collaborative Cross mice and present the first exciting results, both data- and methods-driven, issuing from this cross. CCGS and Genetics faculty member Fernando Pardo Manuel de Villena is the corresponding author on the anchor paper and was featured in a News and Observer front page article as well as a sound byte on NPR last Thursday. Congratulations to Fernando and the other CCGS authors on 11 of the 15 papers which included Fei Zou, Leonard McMillan, Fred Wright, Wei Wang, Will Valdar, Wei Sun and Pat Sullivan.
News and observer article: http://www.newsobserver.com/2012/02/16/1858729/library-of-mice-is-key-to-human.html
UNC Press release: http://news.unchealthcare.org/news/2012/february/north-carolina-based-genetic-resources-fuel-big-scientific-progress
List and links to the 15 papers: http://www.genetics.org/site/misc/MouseGeneticResources.xhtml
CCGS scientists funded to study genome sequencing in clinical settings
December 6, 2011
Link to article in UNC Healthcare News
Praveen Sethupathy recognized as a “rising young investigator” by Genome Technology
December 6, 2011
Congratulations to Praveen Sethupathy, who was selected as a “rising young investigator” by Genome Technology in their sixth annual profile of young PIs recognized for their interesting and thought provoking research in genomics. Praveen joined the UNC department of genetics and the CCGS as an Assistant Professor in September 2011. His profile, and a link to a list of the other selected investigators, are listed below. This is the second year in a row that a CCGS investigator has been recognized. Last year, Jonathan Berg was cited for “clinical cancer genomics”.
Praveen Sethupathy: MicroRNA, Regulation, and Complex Diseases
December 2011/January 2012
By Ciara Curtin (Genome Web)
Recommended by: Francis Collins, NIH
The genes expressed in a cell give that cell its identity and determine its function. Something, however, has to control that gene expression to give the cell stability in a changing environment. The University of North Carolina at Chapel Hill's Praveen Sethupathy wants to know how that control is regulated, particularly in disease. MicroRNAs, he says, are emerging as regulators of cellular robustness.
"That arena is exciting to me because I believe that it's going to advance our basic understanding of mechanisms that underlie this concept of cellular robustness, but it is also going to suggest novel therapeutic strategies for the diseases," he says.
Currently, Sethupathy is applying that idea to the study of type 2 diabetes. He is trying to identify which miRNAs govern the function of the pancreatic islet. "The hope is to be able to understand microRNA networks in ground state, and then be able to decipher how those network interactions — connectivity — is changing in the context of disease or islet dysfunction," he says.
To do so, he and his lab are combining computational and experimental genomics, beginning with next-generation sequencing and then moving to computational models to analyze their sequencing data before moving into cell cultures. For further in vivo validation, he adds, they team up with collaborators.
Publication of note
Sethupathy and his colleague in the Collins lab, Michael Stitzel, published a paper in Cell Metabolism in 2010 in which they profiled the epigenome of the pancreatic islet. This, Sethupathy says, was to better understand transcriptional regulation in the islet and provide insights into the etiology of type 2 diabetes.
And the Nobel goes to…
Rather than winning a Nobel Prize, Sethupathy would prefer to be recognized for helping his students. "If there was some sort of recognition about the impact you've had on your students or your colleagues, I think I'd be really happy about something like that," he says.
Link to article
and complete list of 2011/2012 young investigator award recipients
Large international study discovers common genetic contributions to mental illness
September 19, 2011
A team of over 250 researchers from more than 20 countries have discovered that common genetic variations contribute to a person’s risk of schizophrenia and bipolar disorder. The study of more than 50,000 adults ages 18 and older provides new molecular evidence that 11 DNA regions in the human genome have strong association with these diseases, including six regions not previously observed. The researchers also found that many of these DNA variants contribute to both diseases.
The findings, reported by the Psychiatric Genome-Wide Association Study Consortium and published online Sept. 18, 2011 in two papers in the journal Nature Genetics, represent significant advances in the understanding the causes of these chronic, severe, and debilitating disorders.
Also known as a whole genome association study, a genome-wide association study examines all or most of the genes of different individuals to see how much the genes vary from individual to individual.
“This is the largest study of its kind by far,” said Patrick F. Sullivan, MD, Ray M. Hayworth & Family Distinguished Professor of Psychiatry and professor of genetics at the University of North Carolina at Chapel Hill. Sullivan, a PGC coordinator and principal investigator in the study, is also a member of the UNC Lineberger Comprehensive Cancer Center and the Carolina Center for Genome Sciences.
The study that focused on schizophrenia identified “strong evidence for seven different places in the human genome, five of which were new and two previously implicated, that contain DNA changes that are significantly associated with schizophrenia,” Sullivan said.
And in a joint analysis of a schizophrenia and bipolar disorder sample, the Consortium found three different DNA regions, or loci, in which both disorders reached genome-wide statistical significance. “This tells us that these disorders, which many of us have considered to be separate things, actually share fundamental similarity,” Sullivan said.
“The consortium is the largest research consortium ever in psychiatry and is certainly the largest biological experiment we’ve ever done in the field,” Sullivan said. “We are studying on the order of 90,000 individuals across multiple disorders, while trying to do something for the greater good, which is effectively to go as far and as deep as we can in understanding the genomics of mental illness.”
Study confirms males and females have at least one thing in common: upregulating X
October 24, 2011
In a study published in the journal Nature Genetics, a group of scientists including UNC biologist and CCGS Director Jason Lieb, Ph.D., present experiments supporting a longstanding hypothesis that explains how males can survive with only one copy of the X chromosome. The finding provides clarity to a hotly debated topic in science and provides biologists with more information to interpret experiments involving genetic measurements in males and females.
Women have two X chromosomes, while men have one X and one Y. The lack of a ‘back up’ copy of the X chromosome in males contributes to many disorders that have long been observed to occur more often in males, such as hemophilia, Duchenne muscular dystrophy, and certain types of color blindness. Having only one copy of X and two copies of every other chromosome also creates a more fundamental problem – with any other chromosome, the gene number imbalance resulting from having only one copy would be lethal. How can males survive with only one X?
Biologists have been debating how organisms and cells manage the imbalance between X and other chromosomes for years, with the dominant theory being that both sexes up-regulate the expression of X-linked genes, essentially doubling their expression to “2X” in males and “4X” in females. Then, to correct the imbalance that now appears in females (since they have the equivalent of “4” Xs now and 2 of every other chromosome), females then ‘turn off’ one of the hyperactive X chromosomes, resulting in a balanced “2X” expression of those genes across both sexes.
The advent of new technology based on RNA sequencing and proteomic analysis has given scientists more accurate ways to measure gene expression, and some results published in the last few years have not supported the idea that X chromosomes up-regulate.
Lieb and his colleagues re-analyzed data used in previous analyses, along with new data from humans, mice, roundworms, and fruit flies and found more evidence that the up-regulation hypothesis is correct – but with some interesting twists across species. In mammals – humans and mice – both males and females up-regulate X chromosome gene expression and females then equalize expression by turning off the one X chromosome. In roundworms (C. elegans) both female X chromosomes stay active, but the genes on both Xs are down-regulated by half to compensate in the females. In fruit files (Drosophilia melanogaster), males increase the expression of X chromosome genes, with no upregulation of X in females.
“There are several ways to get the same result and we are seeing how the dosage-balancing mechanism works in different species,” says Lieb. “We also found that not all X-linked genes are dosage compensated to the same degree– adding another layer of complexity for scientists who study gene regulation.”
CCGS faculty funded to develop tools for analysis of Collaborative Cross mouse data
August 29, 2011
The Collaborative Cross (CC) collection of inbred mouse strains maximizes genetic diversity in an inbred mouse model providing a unique resource for systems genetics, gene - environment studies, and predictive biology. The 
goal is to better model the heterogeneous human population, overcoming many of the limitations to studying human complex traits.
A wide array of genomic and phenotypic information is being collected on the CC lines and the F1 hybrids (RIX) derived from the parental lines. Utilization of this data depends on the development of specialized statistical tools. This is the focus of an R01, “Robust Methods for Complex Trait Mapping with the Collaborative Cross”, awarded to Fei Zou (CCGS/Biostatistics) and co-investigators Fred Wright (CCGS/Biostatistics) and Wei Sun (CCGS/Biostatistics). The NIGMS funded project will provide a statistical analysis platform to address unique features of the CC-RIX samples, supporting complex phenotypic analysis, integration of genotype, expression, and phenotype data, and developing strategies for selection of lines for predictive biology. The computational tools developed will also be extended to the analysis of human GWAS data.
Chuck Perou appointed May Goldman Shaw Distinguished Professor of Molecular Oncology Research
August 16, 2011
Charles M. Perou, PhD, professor of genetics, and pathology & laboratory medicine, and leader of the UNC Lineberger Comprehensive Cancer Center breast cancer research program has been appointed the May Goldman Shaw Distinguished Professor of Molecular Oncology Research. The professorship, established by a $1 million gift from Wally (class of ’66) and Lil Loewenbaum of Austin, Texas is named in honor of Mrs. Lowenbaum’s mother, May Goldman Shaw.
Dr. Perou’s research crosses the disciplines of biology, genetics, bioinformatics, epidemiology and the clinical treatment of breast cancer. His most widely cited contribution to the field has been leading an interdisciplinary UNC team that characterized the diversity of breast tumors using genomics, and has classified them in a way that helps physicians better understand why some cancers do not respond to standard therapies and to tailor treatment to the patient’s disease subtype.
He and his colleagues have demonstrated that breast cancer can be classified into five molecular subtypes, with his lab focusing particular attention on the basal-like and claudin-low tumor subtype (known collectively as triple-negative breast cancers), which have a poor prognosis. He is currently studying the genetic mechanisms that give rise to each tumor subtype and is using animal models and human clinical trial samples to define why certain sub-types are resistant to current therapies.
Dr. Perou is also the recipient of the Komen/AACR 2009 Outstanding Investigator Award for Breast Cancer Research and the UNC Hettleman Prize for Artistic and Scholarly Achievement. He earned his BA in Biology at Bates College in Maine, his PhD in Cell Biology at the University of Utah, and performed his postdoctoral work in the laboratory of David Botstein (then of Stanford University). He has been a faculty member at UNC since 2000.
Ian Davis receives grant from Hyundai to study childhood sarcoma
September 2, 2011
Hyundai Hope on Wheels and Raleigh-Durham Area Hyundai Dealers awarded Ian Davis, MD, PhD, a $100,000 grant to support research into the causes of and treatments for pediatric sarcoma. Davis, assistant professor of 
pediatrics and genetics and a member of UNC Lineberger Comprehensive Cancer Center is one of 71 recipients of Hyundai Hope on Wheels’ 2011 Hope Grant program, where $7.1 million will be awarded to support research and programs in honor of National Childhood Cancer Awareness Month.
Davis uses state of the art genome wide techniques to find the causes of childhood sarcomas and on therapies to turn off the genes that are responsible for the growth of sarcoma tumors. Dr. Davis also specializes in the treatment of children with these types of tumors.
“We are working very hard in the laboratory to understand how differences in the structure of DNA causes cancer and to figure out how to counteract the oncogenes – cancer causing genes – that are responsible for the growth of certain types of sarcoma,” said Davis. “As with many rare diseases, government-sponsored research funding is limited. Private philanthropy, such as this grant from Hope on Wheels, is essential to our progress.”
Study links chemotherapy response to heritable factors
Thursday, Oct. 27, 2011
Physicians and scientists know that a patient’s genetic makeup can affect how well a particular drug works for them. Recent findings in pharmacogenomics are enabling safer use of drugs like the anticoagulant warfarin, with fewer side effects for patients. However, the role that genetics plays in the patient response to common chemotherapy drugs had not been evaluated.
A new study from UNC Lineberger Comprehensive Cancer Center and UNC’s Institute for Pharmacogenomics & Individualized Therapy evaluated 29 commonly used cancer chemotherapy drugs in the laboratory and found that the influence of genetics on chemotherapy response varies widely between different drugs and different classes of drugs.
The study was published online in the journal Pharmacogenomics.
The team tested inheritance of chemotherapy drug effect by using cancer cells derived from 14 extended families. Response varied a great deal among the 29 tested drugs. Genetics influenced as little as 15 percent of response to some drugs and as much as 60 percent for others.
The team also found genetic markers that were unique to drugs from the same chemical family.
“Our results can help us and other scientists ‘zoom in’ on the region of the genome that holds clues to why chemotherapy – or certain drug classes of chemotherapy – doesn’t work as well for some people,” said Howard McLeod, PharmD, the project’s principal investigator, Eshelman distinguished professor in the UNC Eshelman School of Pharmacy and a member of UNC Lineberger Comprehensive Cancer Center and Carolina Center for Genome Sciences.
New Genome Science Building scheduled to open in March 2012
The new 210,000 square feet Genome Sciences Building (GSB), located behind the football stadium on Bell Tower Drive, is schedule to open in March 2012. The open design is meant to foster interdisciplinary collaboration and features an abundance of glass and natural light. In addition to 91,000 square feet of wet lab space, offices, and bioinformatics space, the facility will include 11,000 square feet of roof greenhouse space, 450 and 250-seat auditoriums, an 80-seat lecture hall, five 35-seat classrooms, and a cafe.
The Fall 2011 Carolina Arts and Sciences alumni magazine features a 7-page article on the GSB and the interdisciplinary research of several of the faculty that will be housed there including CCGS members Jeff Dangl, Wei Wang, Yufeng Liu, and Jason Lieb.
Please mark your calendars for the symposium that CCGS is organizing to celebrate the opening of the new building and genomics research on campus. This event will take place on October 12, 2012 (University Day) and will feature talks by several leaders in genomics (Evan Eichler, Joe Ecker, David Botstein, and Ruth Ley) as well as a poster session, ribbon cutting/dedication, and reception.
National Science Foundation taps Carolina researchers to develop national data infrastructure
September 28, 2011
The National Science Foundation has funded the University of North Carolina at Chapel Hill to lead a multi-institutional team that will build and deploy a prototype national data management infrastructure that addresses some of the key data challenges facing scientific researchers in the digital age. The infrastructure will support collaborative multidisciplinary research through shared collections, data publication within digital libraries and reference collections within persistent archives.
The NSF awarded nearly $8 million over five years to the DataNet Federation Consortium (DFC), a group that spans seven universities. The DFC will address the data management needs of six science and engineering disciplines: oceanography, hydrology, engineering design, plant biology, cognitive science, and social science. About half the award will support research and development at UNC-Chapel Hill.
The Data Intensive Cyber Environments (DICE) research group in UNC’s School of Information and Library Science (SILS) leads the consortium and RENCI (the Renaissance Computing Institute at UNC-Chapel Hill) is responsible for federating the consortium’s diverse data repositories to enable cross-disciplinary research.
The DFC will use iRODS, the integrated Rule Oriented Data System, to implement a policy-based data management infrastructure. iRODS, developed by UNC’s DICE Center and DICE researchers at the University of California at San Diego, enforces policies as computer actionable rules to organize distributed data into sharable collections. Procedures to automate data management functions are cast as computer executable workflows. Policies control data access, sharing and archiving. Research groups worldwide, including the NASA Center for Climate Simulations, the National Optical Astronomy Observatory, the Australian Research Collaboration Service, and the Texas Digital Libraries, use iRODS technology to manage their research data grids, implement digital libraries, and build persistent archives.
Experts in the DICE group and at RENCI will work with six NSF-supported national consortia to federate their distributed data repositories and create policies for retention, distribution, access and validation of critical data properties. Those communities are:
- The Ocean Observatories Initiative (OOI), an NSF-funded program led by the University of California at San Diego and the Scripps Institution of Oceanography in San Diego. The OOI researchers use data from environmental sensors to study the physical, chemical, geological and biological variables in the ocean and seafloor.
- The Consortium of Universities for Advancement of Hydrologic Science, Inc. (CUAHSI) an organization led by the University of South Carolina. CUAHSI includes more than 130 partner organizations, including UNC’s Institute for the Environment, working to advance water science.
- CIBER-U, the Cyber-Infrastructure-Based Engineering Repositories for Undergraduates, an initiative led by Drexel University, which uses digital design repositories to enhance engineering instruction and learning.
- The iPlant Collaborative, a community of researchers and students led by the University of Arizona that is developing an integrated cyberinfrastructure to advance studies of plant biology.
- The Odum Institute for Research in Social Science, an interdisciplinary institute at UNC-Chapel Hill that focuses on teaching and research in the social sciences.
- The Temporal Dynamics of Learning Center (TDLC), an NSF Science of Learning Center based at the University of California at San Diego that studies the role of time and timing in learning in order to improve educational practices.
Arizona State University researchers will participate in the DFC by collaborating on policy-based data management systems and Duke University researchers will collaborate on education and outreach initiatives to broaden the impact of the DFC.