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Retired Gen. Dan McNeill, commander of  the International Security Assistance Force in Afghanistan in 2007 and 2008, will give a keynote speech at North Carolina State University’s General Hugh Shelton Leadership Forum on Friday, Nov. 5, at the McKimmon Center. Continue Reading »

Republican claims of political corruption in North Carolina’s Democratic Party have made little impact on public opinion among potential voters in the state, according to new polling data analyzed by North Carolina State University researchers. The findings show that highlighting actual corruption is not necessarily an effective electoral strategy. Continue Reading »

Researchers at North Carolina State University have found a way to “cage” genetic off switches in such a way that they can be activated when exposed to UV light. Their technology gives scientists a more precise way to control and study gene function in localized areas of developing organisms.

The off switches,  called morpholino oligonucleotides, are like short snippets of DNA that, when introduced into cells, bind to target RNA molecules, effectively turning off specific genes. Morpholinos have been used as genetic switches in many animal models, including the zebrafish embryo. However, morpholinos are distributed throughout dividing cells in a developing embryo, thereby turning off the specific gene everywhere. Moreover, they are active right after injection, silencing the targeted gene throughout development of the organism. Such uncontrolled genetic disruption makes studying tissue-specific and time-specific gene function difficult.

Dr. Alex Deiters, associate professor of chemistry, Dr. Jeffrey Yoder, associate professor of molecular biomedical sciences, and a team of NC State researchers developed a new methodology to turn off genes at a specific time and in a specific region of an organism. Deiters’ team devised a way to synthesize morpholinos that would only bind with RNA molecules after a brief exposure to UV light, effectively “caging” the morpholino and providing a method for precisely controlling the genetic off switch. Yoder’s team then tested the new photo-caged morpholinos in a zebrafish model and confirmed that they performed as expected: the caged morpholinos did not disrupt gene function unless the embryos were briefly exposed to UV light.

The researchers’ results appear  online in the Journal of the American Chemical Society.

The research was funded by grants from the National Institutes of Health. The Department of Molecular Biomedical Sciences is part of NC State’s College of Veterinary Medicine. The Department of Chemistry is part of NC State’s College of Physical and Mathematical Sciences. Deiters and Yoder are members of NC State’s Center for Comparative Medicine and Translational Research.

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Note to editors: An abstract of the paper follows.

“Photocaged Morpholino Oligomers for the Light-Regulation of Gene Function in Zebrafish and Xenopus Embryos”
Authors: Alexander Deiters, R. Aaron Garner, Hrvoje Lusic,  Jeane M. Govan, Mike Dush, Nanette M. Nascone-Yoder, and Jeffrey A. Yoder, NC State University
Published: online in the Journal of the American Chemical Society

Abstract: Morpholino oligonucleotides, or morpholinos, have emerged as powerful antisense reagents for evaluating gene function in both in vitro and in vivo contexts. However, the constitutive activity of these reagents limits their utility for applications that require spatiotemporal control, such as tissue-specific gene disruptions in embryos. Here we report a novel and efficient synthetic route for incorporating photocaged monomeric building blocks directly into morpholino oligomers and demonstrate the utility of these caged morpholinos in the light-activated control of gene function in both cell culture and living embryos. We demonstrate that a caged morpholino that targets enhanced green fluorescent protein (EGFP) disrupts EGFP production only after exposure to UV light in both transfected cells and living zebrafish (Danio rerio) and Xenopus frog embryos. Finally, we show that a caged morpholino targeting chordin, a zebrafish gene that yields a distinct phenotype when functionally disrupted by conventional morpholinos, elicits a chordin phenotype in a UV-dependent manner. Our results suggest that photocaged morpholinos are readily synthesized and highly efficacious tools for light-activated spatiotemporal control of gene expression in multiple contexts.

Researchers at North Carolina State University have found that the overproduction of a key protein in stem cells causes those stem cells to form cancerous tumors. Their work may lead to new treatments for a variety of cancers.

Dr. Jon Horowitz, associate professor of molecular biomedical sciences, and a team of NC State researchers looked at the protein SP2, which regulates the activity of other genes. They knew that elevated amounts of SP2 had been observed in human prostate-cancer patients, and that these levels only increased as the tumors became more dangerous. They then showed that precisely the same thing occurs in mouse skin tumors.

Horowitz and the team decided to look at SP2 as a possible cause of tumor formation in epithelial cell-derived tumors, which comprise about 80 percent of all human tumors; epithelial cells cover the body’s internal and external surfaces. They found that overproduction of the SP2 protein in epithelial stem cells stopped them from spawning mature descendants. The affected stem cells, unable to produce mature cells, just kept proliferating, resulting in the formation of tumors.

The researchers’ results are published in the Nov. 3 edition of the journal Cancer Research.

“Something happens to normal stem cells that changes the way SP2 is regulated, and it starts being overproduced,” Horowitz says. “SP2 basically hijacks the stem cell, and turns it into its evil twin – a cancer cell.”

Now that the link between tumor formation and SP2 has been shown, Horowitz says, scientists can turn their attention to looking at ways to target the overproduction of this protein. “Our hope is that we can find an ‘antidote’ to SP2, to restore normal cell proliferation to those cancer stem cells and reverse the process.”

The research was funded by a grant from the National Institutes of Health (NIH). The Department of Molecular Biomedical Sciences is part of NC State’s College of Veterinary Medicine.

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Note to editors: Abstract of the paper follows.

“Overexpression of Transcription Factor Sp2 Inhibits Epidermal Differentiation and Increases Susceptibility to Wound and Carcinogen-Induced Tumorigenesis”
Authors: Tae-Hyung Kim, Shannon L. Chiera, Keith E. Linder, Robert C. Smart, and Jonathan M. Horowitz, NC State University; Carol S. Trempus, Metabolism and Molecular Mechanisms Group, Laboratory of Toxicology and Pharmacology, NIH, NIEHS
Published: Nov. 3 in Cancer Research

Abstract: Sp proteins are evolutionarily-conserved transcription factors required for the expression of a wide variety of genes that are critical for development and cell-cycle progression. De-regulated expression of certain Sp proteins is associated with the formation of a variety of human tumors, however direct evidence that any given Sp protein is oncogenic has been lacking. Here we report that Sp2 protein abundance in mice increases in concert with the progression of carcinogen-induced murine squamous cell carcinomas. Transgenic mice specifically overexpressing murine Sp2 in epidermal basal keratinocytes were highly susceptible to wound- and carcinogen-induced papillomagenesis. Transgenic animals that were homozygous rather than hemizygous for the Sp2 transgene exhibited a striking arrest in the epidermal differentiation program, perishing within two weeks of birth. Our results directly support the likelihood that Sp2 overexpression occurring in various human cancers has significant functional impact.

Dr. Randy Woodson will be formally installed as North Carolina State University’s 14th chancellor during an event at 10:30 a.m. on Tuesday, Oct. 26, in Reynolds Coliseum. Media coverage is invited. Parking is available in Jeter Bays deck off Jeter Drive, east of Reynolds Coliseum. Media should request a parking pass from News Services by calling 515-8387 or e-mailing mick_kulikowski@ncsu.edu.

The installation ceremony is part of a week’s worth of activities centered around the theme, “Locally responsive. Globally engaged.” Seminars, socials and strategic-planning sessions are also on tap.

Woodson was named chancellor on Jan. 8 and began work on April 5. He previously served as provost at Purdue University.

For more information about the installation or installation-week activities, visit the Web.

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The Bill & Melinda Gates Foundation and MDC, a nonprofit organization dedicated to expanding opportunity and reducing poverty, today announced that Raleigh has been selected as one of four cities to participate in the Partners for Postsecondary Success (PPS) initiative as part of a Gates-funded national effort to improve postsecondary completion rates among low-income young adults. Continue Reading »

North Carolina State University will host a presentation by Robert M. Groves, director of the U.S. Census Bureau, on Monday, Oct. 18, at 3 p.m. Groves will discuss the design of the census, the data-collection process and how the data is being tabulated and evaluated.

Media are invited to attend. Groves will be available for interviews following the presentation, which will be held in 323 Mann Hall on the NC State campus.

The lecture is hosted by the Department of Statistics, part of NC State’s College of Physical and Mathematical Sciences.

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