April 17, 2009

Aliquots — research highlights from VUMC laboratories

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.


Teaching tolerance to B cells

As a protection against autoimmune diseases, antibody-producing B cells often exist in a state of “tolerance” in which they fail to recognize and attack the body’s own parts. But the mechanisms that establish and maintain tolerance in immature B cells (found in bone marrow) are not well understood – particularly in response to small hormone proteins like insulin, a key autoantigen in type 1 diabetes.

Using a bone marrow culture system, Rachel Henry, a graduate student working with James Thomas, M.D., found that immature B cells genetically programmed to recognize insulin develop signs of tolerance similar to those seen in mature B cells after short-term exposure to insulin. These tolerance features were reversed upon insulin removal, suggesting that constant antigen (insulin) engagement is required to maintain tolerance and to prevent insulin autoimmunity.

The results, in the March 15 Journal of Immunology, indicate that tolerance is initiated by insulin in developing B cells in the bone marrow and point to a window of opportunity for preventing insulin autoimmunity.

Melissa Marino


Embryos shape up with G proteins

During early vertebrate development, the simple and symmetrical embryo reshapes itself to reveal its fundamental body plan. This process – called gastrulation – involves cooperative cellular movements, whose underlying molecular mechanisms have not been fully defined.

In the March 23 issue of The Journal of Cell Biology, Fang Lin, Ph.D., Heidi Hamm, Ph.D., Lilianna Solnica-Krezel, Ph.D., and colleagues establish the proteins Ga12 and Ga13 as novel regulators of epiboly – one of the phases of gastrulation – in zebrafish. They provide in vivo evidence that Ga12/13 signaling can regulate different aspects of epiboly cell movements by two distinct mechanisms: inhibiting activity of E-cadherin (a cell adhesion protein) and modulating actin cytoskeleton organization.

Because Ga12/13 and E-cadherin have been implicated in tumor development and metastasis, the current findings may offer insights on the roles of these molecules in cancer biology as well as in other tissue- and organ-forming processes during development.

Leigh MacMillan


Cancer fusion protein disarms silencer

Synovial sarcoma is rare, aggressive soft tissue cancer – usually near the arm and leg joints – that typically afflicts young adults. A genetic rearrangement that produces one of two fusion proteins (SYT-SSX1 or SYT-SSX2) is present in more than 95 percent of synovial sarcoma tumors. But how these fusion proteins influence disease is not clear.

In PLoS ONE, Josiane Eid, M.D., and colleagues report that SYT-SSX2 protein interferes with the function of the polycomb repressive complex – a set of proteins that typically inhibits gene expression by remodeling the structure of chromatin (the DNA and proteins that constitute chromosomes).

Using human osteosarcoma (bone cancer) cells, they show that SYT-SSX2 destabilizes components of the polycomb complex, leading to the reactivation of genes that would normally be silenced. Although increased polycomb function has been recently implicated in some cancers, the current study demonstrates that expression of SYT-SSX2 can also lead to loss of polycomb function, suggesting that any imbalance in polycomb activity could drive cancer formation.

Melissa Marino


Program improves data collection

Biomedical research – particularly in the clinical and translational realm – often involves collaborations by many scientists in diverse locations. But collecting, storing and sharing data in a secure manner across academic departments or even institutions is challenging.

Paul Harris, Ph.D., and colleagues have developed a data collection and sharing platform to support clinical and translational research.

In the April issue of the Journal of Biomedical Informatics, the researchers describe the Web-based program they call REDCap (Research Electronic Data Capture). They explain the REDCap toolset and give details concerning the capture and use of study-related data. Initially launched in August 2004, the REDCap system quickly gained a wide reputation at Vanderbilt as a toolset and workflow method for providing secure, Web-based data collection services. The program currently supports nearly 500 translational research projects and 1,800 end-users in a growing collaborative network including 44 active partner institutions (see www.project-redcap.org).

Leigh MacMillan

Past Aliquots

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