February 2, 2012

Aliquots — research highlights from VUMC laboratories


Drugs reverse lung cancer cell changes

The protein transforming growth factor β (TGF-β) can act as either a tumor suppressor or a tumor promoter depending on the stage of cancer. Loss of TGF-β’s tumor suppressor activity may play an important role in lung cancer progression.

Pran Datta, Ph.D., and colleagues previously showed that this loss of responsiveness to TGF-β occurs mainly through loss of expression of the TGF-β type II receptor (TβRII). However little is known about the mechanisms underlying this loss of expression – or how it might be restored.

In a recent study published in Neoplasia, Datta and colleagues identify several proteins/pathways involved in regulating TβRII expression in lung cancer cell lines, and that histone deacetylation – an “epigenetic” change that modulates gene expression – is involved in the loss of TβRII expression in lung cancer cells. Additionally, drugs called histone deacetylase inhibitors (HDIs) were shown to restore expression of TβRII, suggesting that these compounds – either alone or in combination with other agents – may hold potential in treating or slowing the progression of lung cancer.

The research was supported by grants from the National Cancer Institute and the Department of Veterans Affairs.

Melissa Marino


Treatment window for genetic disorder




In the January issue of Neurobiology of Disease, Kevin Ess, M.D., Ph.D., and colleagues show that mice genetically engineered to lack Tsc1 in the brain die prematurely, have increased brain size, and have various anatomical and cellular abnormalities in both neurons and glia (the supporting cells in the brain). Additionally, activity of the “mammalian target of rapamycin complex” (mTORC1 and mTORC2) pathways was altered in brain cells, and treatment with rapamycin (a drug commonly used to combat organ rejection) prevented premature death and reversed glial abnormalities. The results suggest that a postnatal treatment window may exist for combating some of the neurological and cognitive effects of TSC.

The research was supported by the National Institute of Neurological Disorders and Stroke, the Tuberous Sclerosis Alliance, and the Vanderbilt Kennedy Center for Research on Human Development.

Melissa Marino


Tool finds connections in genome data

Genome-wide association studies (GWAS) have identified hundreds of genetic variants that increase a person’s susceptibility for complex diseases. Although these variants have added to our understanding of disease pathology, they usually account for only a small proportion of disease risk.



Zhongming Zhao, Ph.D., and colleagues have developed an approach to identify gene variants that act together – for example in a biological pathway – and have a joint effect on disease risk. Their method builds on the generalized additive model (gamGWAS). It eliminates a previously identified problem in the analysis of gene sets (the long gene bias) and does not require genotyping data from the original GWAS, which reduces computational burden.

The investigators used gamGWAS to analyze two existing schizophrenia GWAS datasets from the International Schizophrenia Consortium and the Genetic Association Information Network. They report in the February Journal of Medical Genetics that gamGWAS confirmed previous findings in these datasets and also pointed to new immune-related pathways that may have roles in schizophrenia.

This research was supported by the National Institute of Mental Health, a NARSAD Maltz Investigator Award and a NARSAD Young Investigator Award.

Leigh MacMillan


Matchmaker for clinical studies

In a collaborative project for institutions in the Clinical and Translational Science Awards (CTSA) consortium, Paul Harris, Ph.D., and colleagues designed ResearchMatch, a web-based national recruitment registry to help match individuals who wish to participate in clinical research studies with researchers actively searching for volunteers (www.researchmatch.org). In the January issue of Academic Medicine, the investigators describe ResearchMatch’s design, technical infrastructure, workflow model and utilization metrics. As of June 2011, ResearchMatch had registered 15,871 volunteer participants from all 50 states and 751 researchers from 61 CTSA institutions (current numbers on the website show 20,192 volunteers, 1010 researchers and 67 institutions).

ResearchMatch has proven successful in connecting volunteers with researchers, and the developers are currently evaluating regulatory and workflow options to open access to researchers at non-CTSA institutions.

This research was supported by the National Center for Research Resources.

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