September 22, 2011

Aliquots — research highlights from VUMC laboratories


A boost for radiation’s killing power

Radiation therapy – ionizing radiation that kills cells by producing DNA damage – is an important tool for treating human cancer. Because cancer cells can acquire resistance to radiation, Sekhar Konjeti, Ph.D., Michael Freeman, Ph.D., and colleagues are searching for ways to enhance the DNA damage produced by ionizing radiation in order to overcome cancer cell resistance.

The investigators have now identified a novel chemical entity (YTR107) that enhances the sensitivity of several different cancer cell lines to radiation. They report Aug. 30 in Clinical Cancer Research that YTR107, which has been patented by Vanderbilt, targets a protein called nucleophosmin that has a role in DNA repair. They demonstrated that YTR107 blocks phospho-nucleophosmin shuttling to the sites of radiation-induced DNA damage.

These findings support the idea that blocking DNA damage repair – through a novel pathway (nucleophosmin shuttling) – is an effective strategy for sensitizing cancer cells to the killing effects of ionizing radiation and increasing the efficacy of radiation therapy.

Leigh MacMillan


Kif18A’s tail goes the distance

Wellcome Images

Wellcome Images

In the Sept. 2 issue of Molecular Cell, Ryoma Ohi, Ph.D., and colleagues identify the protein’s “tail” section as being crucial to its function. By creating Kif18A mutants, they showed that accumulation of the protein at microtubule plus-ends depends on the C-terminal tail domain, whereas suppression of microtubule growth depends on the N-terminal motor domain. The tail region works by “tethering” the motor to the microtubule track, thereby increasing the distance that the protein can move along microtubules.

Since some chemotherapy drugs, like Taxol, act by disrupting microtubule dynamics, the findings may have implications for cancer therapeutics.

Melissa Marino


Protein trio ups gastric cancer risk

Helicobacter pyloriH. pyloricagcag

Timothy Cover, M.D., and colleagues used mass spectrometry and electron microscopy tools to reveal that three cag PAI proteins (CagH, CagI and CagL) are involved in the formation of hair-like structures called pili on the bacterial surface. These proteins – and the pili they produce – are essential for moving CagA into the gastric epithelial cells, where it promotes cellular changes that can lead to the development of cancer.

The findings in the September issue of PLoS Pathogens reveal unique components of the H. pylori secretion system and demonstrate that this system varies from previously characterized bacterial secretion systems.

Leigh MacMillan


Seeing through skin proteins

Lillian Nanney, Ph.D., Richard Caprioli, Ph.D., and colleagues employed two advanced Imaging Mass Spectrometry methods (MALDI-IMS) to detect and spatially define protein signatures in normal human skin. They report, in the August issue of Experimental Dermatology, that these methods can detect patterns of protein differences between the epidermis (the outer skin layer) and the dermis (the thick layer below the epidermis that contains sweat glands, hair follicles and capillaries) – as well as differences between different regions of the dermis. In addition, the mass spectrometry methods were able to detect proteins that may vary between individuals, suggesting that these methods may be applicable in the realm of individualized medicine.

Melissa Marino


We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012