IMA offers powerful tools to aid translational researchers

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Clinical and translational researchers have access to new intellectual and technical resources and specialized instrumentation and technologies in the Integrated Molecular Analysis facility (IMA).

Andra Frost examine a tissue sample on the laser-
capture microdissection instrument in the Integrated Molecular Analysis facility.
The IMA provides a centralized resource for tissue preparation, gene-expression analysis and protein quantification. Instrumentation and technologies available include laser capture microdissection, real-time PCR including Taqman Low Density Arrays, and quantitative proteomics analysis using a Meso Scale Imager.

“This is impossible for many independent labs to set up on their own,” says Martin Johnson, Ph.D., director of the facility. “This is a central place to go and incorporate the analysis into your research without the need to spend a tremendous amount of time and expense trying to figure out how to do it and where to do it, likely while borrowing other people’s equipment.

“Researchers have the ability to prepare their tissues or samples for RNA, DNA or protein analysis, run genetic or protein tests in one comprehensive place and get all of the information they are seeking,” Johnson says. “We have a laser-capture microdissection facility, a gene-expression facility and a protein-analysis facility, and they all use separate instrumentation. They all run different standards.”

The IMA is capable of analyzing a variety of samples, including snap-frozen tissues, fine needle aspirates, archived paraffin-embedded tissues, in vitro cell lines and in vivo xenograft tissues.

The IMA facility supports intra- and extra-mural research projects through access to selected advanced instruments and methodology performed by personnel with demonstrated expertise. Results often can be provided in just a few days.

“Collectively, this facility will provide the intellectual and technical resources that can assist the investigator in designing and conducting experiments, preparing the appropriate samples for analysis, analyzing them in the most appropriate way and assisting in interpreting the results,” Martin says. “We have a lot of experience dealing with difficult tissues, including clinical samples like needle biopsies. They’re very tough to analyze, but we have the skill and experience to do it.”

Translational research
Albert LoBuglio, M.D., associate director for clinical research in the UAB Comprehensive Cancer Center, has been using the IMA technology to explore the mechanisms that account for resistance of breast cancers to treatment with anti-estrogens and to demonstrate the mechanisms for a new treatment of breast cancer using anti-estrogens and anti-angiogenesis, or an inhibition of tumor blood flow.

“The Cancer Center is deeply involved in translational — or bench to bedside — research that requires the ability to measure the expression of multiple genes and biologic pathways in individual human tumors,” LuBuglio says. “This technology enables us to identify patient tumors that are most likely to respond to a specific therapy. We can better determine why some patients respond or are resistant to various treatments and the effects that occur with specific therapies, and we can analyze mechanisms that are responsible for tumor behaviors.”

Johnson says the facility enables the re-searcher to expand their projects by providing tissue analyses in an integrated platform that would be inefficient or impractical for individual projects to support. This is possible through more comprehensive testing on smaller tissue samples using a wider variety of advanced methods.

The IMA facility can:

  • Provide laser-capture microdissection using two different instruments
  • Provide real-time quantitative polymerase chain reaction, Taqman low-density array and single nucleotide polymorphism analysis of human and animal tissues
  • Provide multiplex protein quantification using the MESO scale diagnostics platform.

 

The facility aims to be Clinical Laboratory Improvement Amendments-certified (CLIA) by the end of the year. Results from the IMA facility labs can be used for clinical diagnosis once the certification is granted; that means patients in clinical trials can have their treatment altered by their physicians based on the findings in the lab.

Powerful equipment
Analyzing gene expression with the Taqman low-density array (TLDA) is a key component to translational research, Johnson says.

“A researcher can examine the expression of up to 384 genes in just two hours. This makes it possible to examine complete pathways” says Johnson, who helped in the development and validation of the TLDA technology. “It’s very, very powerful. Most people don’t even know this technology exists, and most universities don’t have it.”

The laser microdissection instruments and the MESO Scale Imager have well-known histories as well.

The Laser Microdissection Facility was established in 1998 under the direction of Andra Frost, M.D., IMA co-director, by the UAB Comprehensive Cancer Center and the Department of Pathology.
Data obtained by the MESO Scale Imager detects proteins from formalin-fixed, paraffin-embedded and frozen tissues, body fluids and fine-needle aspirates and proteins obtained from a variety of protocols used in basic science laboratory research. Thus, the potential uses of the instrument for protein quantification are “virtually unlimited,” Johnson says.

“When you couple laser microdissection, TLDA and the MESO Scale technology you get the ability to perform a comprehensive analysis (capable of determining mRNA or protein levels) on virtually any clinical biopsy,” Johnson says.

To learn more about the IMA and its capabilities, visit peir.path.uab.edu/coreweb/ or contact Johnson at martin.johnson@ccc.uab.edu.