February 19, 2010

Aliquots — research highlights from VUMC laboratories


Better estimates of cervical disease

Cervical cancer is the leading cause of cancer deaths among women in India, and HIV-infected Indian women are at particularly high risk. However, the standard screening method – cervical cytology, or Pap smear – may be underestimating the true burden of disease in this population.

Vikrant Sahasrabuddhe, M.D., Dr.PH, and colleagues are trying to improve detection (and therefore prevalence estimates) of precancerous cervical lesions by combining the standard Pap smear test with visual inspection of the cervix using colposcopy and by histopathological analysis of suspected colposcopic abnormalities. Using the combination of detection methods, they found that more than a quarter of HIV-positive Indian women (27.7 percent) had evidence of early precancerous lesions, and that one-sixth (16.5 percent) had more advanced lesions. Additionally, 41.7 percent were infected with HPV (human papillomavirus), the primary cause of cervical cancer.

The study in PLoS ONE provides the first estimates using the combined screening method and highlight a substantial burden of cervical precancerous lesions – which can progress to invasive cancer if not treated – in this population.

Melissa Marino


Cancer clues in cell’s ‘power plants’

The mitochondria – the small cellular structures that produce chemical energy that powers the cell – have their own genome, which is particularly sensitive to damage by environmental carcinogens. Several mutations in the “D-loop” region of mitochondrial DNA (mtDNA) – which regulates mtDNA replication and transcription – have been identified in breast cancer tissue.

To determine how these mutations are associated with breast cancer risk, Qiuyin Cai, M.D., Ph.D., and colleagues compared tumor tissue and adjacent non-tumor tissue from both breast cancer patients and patients with benign breast disease. They identified five common mutation patterns and determined that differences in the mutation patterns between tumor and non-tumor tissue were more common in breast cancer patients (28.3 percent) than in benign breast disease patients (15.3 percent).

The results, in the January issue of Breast Cancer Research & Treatment, suggest that mutations in this region of mtDNA may play a role in breast cancer development – and, more generally – that mutations in mtDNA could provide markers for cancer development.

Melissa Marino


A scaffold for assembling memories

At the cellular level, the processes of learning and memory are attributed to changing connections between neurons – strengthening some, deleting others. This “synaptic plasticity” requires a precisely coordinated series of molecular changes, which are often driven by changes in calcium levels. The calcium-dependent enzyme CaMKII plays a central role in translating calcium flux into synaptic changes.



In the Jan. 8 Journal of Biological Chemistry, Roger Colbran, Ph.D., and colleagues add new details to CaMKII’s actions. They report that CaMKII binds to and chemically modifies (phosphorylates) a specific variant of SAP97 – a protein that appears to serve as a scaffold for complexes of signaling proteins. This modification of SAP97 disrupts binding of another protein (AKAP79/150) and alters the regulation of glutamate receptors by the proteins PKA and calcineurin, which plays a key role in synaptic plasticity.

The findings suggest a model for the precise coordination of protein-protein interactions and phosphorylation events that are required for normal learning and memory.

Leigh MacMillan


Genes share rhythm-disrupting ways

Atrial fibrillation (AF), an irregular rhythm in the heart’s upper chambers, can cause palpitations, shortness of breath, lightheadedness, and even stroke. Although genetic mutations have been identified in inherited forms of AF, the underlying mechanisms – and implications for therapy – remain unclear.



In a study of 231 participants in the Vanderbilt AF Registry, Robert Abraham, M.D., and colleagues identified mutations in two genes (KCNQ1 and NPPA) in different families with AF. They examined the consequences of the gene changes in vitro and found that both types of mutations increased a certain type of cardiac potassium current in cultured cells. Computational models based on the observed changes in potassium current demonstrated that the mutations shortened the atrial electrical cycle (the action potential), which increases susceptibility to AF.

The study in the January Journal of Molecular and Cellular Cardiology is the first to report that diverse genetic defects associated with AF share a common mechanism and suggests the possibility of mechanism-based therapies for this common disorder.

Leigh MacMillan


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: aliquots@vanderbilt.edu.

Past Aliquots

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