Lab News

September 2014 Congratulations to Kate and Catherine!

Both Kate Hacker and Catherine Fahey are authors on the cover article of Cancer Cell's September 2014 issue!

The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.

February 2014 Congratulations to Kate and Alex!

Both Kate Hacker and Alexandra Arreola have successfully defended their theses in February of 2014. We wholeheartedly congratulate them on this wonderful accomplishment.

February 2014 Brooks et. al. accepted for publication in European Urology

The ClearCode34 biomarker was used to classify tumors in to good, intermediate, and poor risk groups, outperforming conventional clinical risk algorithms. In press in European Urology

February 2014 Upcoming Thesis Defences!

Kate Hacker - February 20, 2014 at 9:00 AM, in the Bioinformatics Building, Room 1131
Alexandra Arreola - February 25, 2014 at 1:30 PM, in the Bioinformatics Room 1131

December 2013 Samira Brooks Wins a Travel Award from the Society of Toxicology

The Society of Toxicology’s (SOT) 53rd Annual Meeting and ToxExpo will be held March 23–27, 2014, at the Phoenix Convention Center in Phoenix, Arizona. The SOT Annual Meeting is the largest meeting of its kind. This annual event features a broad range of scientific sessions and a thematic program that provides participants with a unique opportunity to deepen their knowledge in topical areas and interact with leaders in their respective disciplines. The scientific program includes a plenary session, the MRC Lecture, symposia, workshops, roundtable discussions, informational sessions, historical highlights sessions, as well as platform and poster sessions. The Society anticipates that more than 6,500 toxicologists from more than 50 countries will attend. The SOT Annual Meeting also features the ToxExpo, which is the largest exhibition, dedicated to toxicology and the biomedical sciences. The exhibition features 350 exhibitors, exhibit-hosted sessions, and the opportunity to debut cutting-edge products, services, and technologies.

October 2013 Kate Hacker's Paper is Published in the Genome Research

Congratulations to Kate Hacker, whose paper has been accepted and published by Genome Research. The paper was published online on December 26, 2013. Please read below for a brief overview of the paper, and click here to access the full article online.

Variation in chromatin accessibility in human kidney cancer links H3K36 methyltransferase loss with widespread RNA processing defects.

Comprehensive sequencing of human cancers has identified recurrent mutations in genes encoding chromatin regulatory proteins. For clear cell renal cell carcinoma (ccRCC), three of the five commonly mutated genes encode the chromatin regulators PBRM1, SETD2, and BAP1. How these mutations alter the chromatin landscape and transcriptional program in ccRCC or other cancers is not understood. Here, we identified alterations in chromatin organization and transcript profiles associated with mutations in chromatin regulators in a large cohort of primary human kidney tumors. By associating variation in chromatin organization with mutations in SETD2, which encodes the enzyme responsible for H3K36 trimethylation, we found that changes in chromatin accessibility occurred primarily within actively transcribed genes. This increase in chromatin accessibility was linked with widespread alterations in RNA processing, including intron retention and aberrant splicing, affecting ∼25% of all expressed genes. Furthermore, decreased nucleosome occupancy proximal to misspliced exons was observed in tumors lacking H3K36me3. These results directly link mutations in SETD2 to chromatin accessibility changes and RNA processing defects in cancer. Detecting the functional consequences of specific mutations in chromatin regulatory proteins in primary human samples could ultimately inform the therapeutic application of an emerging class of chromatin-targeted compounds.

September 2013 Neal Rasmussen Defends his PhD Thesis

Congratulations to Neal Rasmussen, who successfully defended his PhD Thesis on September 25, 2013. We wholeheartedly congratulate him on this wonderful accomplishment.

September 2013 Dr. Zufan Debebe Wins the AACR Travel Award

Congratulations Zufan Debebe, winner of an American Association for Cancer Research (AACR) Travel Award. Please click here for more information about AACR travel awards.

July 2013 Neal Rasmussen's Paper is Published in the Journal of Biological Chemistry

Congratulations to Neal Rasmussen, whose paper has been accepted and published by the Journal of Biological Chemistry. The paper was published online on July 26, 2013. Please read below for a brief overview of the paper, and click here to access the full article online.

Receptor Tyrosine Kinase-like Orphan Receptor 2 (Ror2) Expression Creates a Poised State of Wnt Signaling in Renal Cancer.

Expression of the receptor tyrosine kinase-like orphan receptor 2 (Ror2) has been identified in an increasing array of tumor types and is known to play a role as an important mediator of Wnt signaling cascades. In this study, we aimed to clarify Ror2 interactions with the Wnt pathways within the context of renal cell carcinoma (RCC). An examination of Ror2 expression in primary human RCC tumors showed a significant correlation with several Wnt signaling genes, including the classical feedback target gene Axin2. We provide evidence that Ror2 expression results in a partially activated state for canonical Wnt signaling through an increased signaling pool of β-catenin, leading to an enhancement of downstream target genes following Wnt3a stimulation in both renal and renal carcinoma-derived cells. Additionally, inhibition of low-density lipoprotein receptor-related protein 6 (LRP6) with either siRNA or dickkopf decreased the response to Wnt3a stimulation, but no change was seen in the increased β-catenin pool associated with Ror2 expression, suggesting that LRP6 cofactor recruitment is necessary for a Wnt3a-induced signal but that it does not participate in the Ror2 effect on β-catenin signaling. These results highlight a new role for Ror2 in conveying a tonic signal to stabilize soluble β-catenin and create a poised state of enhanced responsiveness to Wnt3a exogenous signals in RCC.

May 2013 Kate Hacker wins the Gertrude B. Elion Mentored Medical Student Research Award

Congratulations to Kate Hacker, winner of the Gertrude B. Elion Mentored Medical Student Research Award. The Gertrude B. Elion Mentored Medical Student Research Award will provide an annual award to one student in the amount of $10,000. These awards will support women medical students who are interested in pursuing health-related research projects. Students must have an interest in health research, and must have the support of a faculty mentor. Please click here for more information about the award.

Gertrude Belle Elion (January 23, 1918 – February 21, 1999) was an American biochemist and pharmacologist, and a 1988 recipient of the Nobel Prize in Physiology or Medicine. Working alone as well as with George H. Hitchings, Elion developed a multitude of new drugs, using innovative research methods that would later lead to the development of the AIDS drug AZT.

April 2013 Sudarshan Mohan wins a SURF Award

Congratulations to Sudarshan Mohan, winner of a Summer Undergraduate Research Fellowship Award. Please click here for more information about the award.

March 2013 Dr. Zufan Debebe wins a 2013 UNCF/Merck Science Initiative Award

Congratulations to Dr. Zufan Debebe, who has won the 2013 UNCF Merck Postdoctoral Science Fellowship, an award targeted towards providing opportunities for post-doctoral fellows to conduct original research. Please click here for more information about the award.

February 2013 Congratulations to Samira Brooks

Congratulations to Samira Brooks, who won third place for her poster entitled "Prognostic biomarker discovery for a distinct gene signature in clear cell Renal Cell Carcinoma" at the Spring 2013 North Carolina Society of Toxicology (NC SOT) meeting at the U.S. Environmental Protection Agency in Research Triangle Park, NC. A brief overview of her project is given in the January 2013 Rathmell Lab news update (below). Please click here for more information on the Spring 2013 NC SOT Meeting.

January 2013 Congratulations to Samira Brooks

Congratulations to Samira Brooks, who won first prize for her poster entitled "Prognostic biomarker discovery for a distinct gene signature in clear cell Renal Cell Carcinoma" at the 2013 UNC Toxicology program retreat. Below is a brief overview of her project:

The incidence of adult Renal Cell Carcinoma (RCC), or kidney cancer, is on a steady rise in the western world, with approximately 100,000 people affected in the United States and Europe in 2010. There are multiple subtypes of this disease, however, over 70% of patients with renal tumors have the clear cell (ccRCC) subtype, a tumor only recently found to be associated with a high degree of heterogeneity, that involves distinct genetic signatures. Genetic signatures have also been established as renal toxicant exposure biomarkers, which can serve as indicators of past renal injury and initial events of kidney cancer. Exploring the range of genome-wide expression alterations as a result of tumor heterogeneity and chronic toxicant exposure will enhance the understanding of this disease and shed light on future methods to provide a personalized care plan for patients with ccRCC.

December 2012 Kate Hacker Receives the Lineberger Cell Biology Training Grant

Congratulations to Kate Hacker (Genetics and Molecular Biology), the recipient of the Lineberger Cancer Cell Biology Training Grant. This grant supports talented students to develop a well-rounded experience integrating basic science concepts with the detection, diagnosis, and treatment of cancer. Grant support covers two years of training, and students participate in focused coursework, career development programming, and annual retreats. Click "read more" for more information on this award. Read more.

October 2012 Congratulations to Dr. Zufan Debebe

Congratulations to Zufan Debebe, PhD, the recipient of a Lineberger Postdoctoral Fellowship for 2012-2014. Click "read more" for more information on this award. Read more.

August 24, 2012 Dr. Rathmell Gives Keynote Speech

Dr. Rathmell was a featured speaker alongside UNC Head Basketball Coach Roy Williams at the American Cancer Society's Action Network breakfast held in RTP. Dr. Rathmell spoke about her American Cancer Society funded project. Read more.