October 2012

Two more Tabor young investigators

At meeting in the Netherlands, Catherine Bell was lauded for project on T-cell–mediated drug-hypersensitivity reactions

Photo of Catherine Bell 

Catherine Bell, a doctoral student at the Medical Research Council Centre for Drug Safety Science at the University of Liverpool, won a Journal of Biological Chemistry/Herb Tabor Young Investigator award in June at the 19th International Symposium on Microsomes and Drug Oxidations and 12th European International Society for the Study of Xenobiotics Meeting in Noordwijk aan Zee, Netherlands. Bell was acknowledged for her work on the role of metabolism in drug hypersensitivity reactions.

Drug-induced, T-cell–mediated hypersensitivity reactions are a cause of concern for clinicians and pharmaceutical companies. They are usually detected during late stages of drug development and occur at low frequency; however, they remain a cause of mortality.

“I am particularly interested in the drug abacavir,” a nucleoside analog used to treat AIDS and known by the brand name Ziagen, Bell said. “This is quite a hot topic at the moment, and a lot of new data has recently emerged suggesting novel mechanisms of drug interaction with T cells.”

Bell explains that patients expressing the HLA-B*57:01 allele are at significantly increased risk of abacavir hypersensitivity reactions. In fact, the U.S. Food and Drug Administration recommends pretherapy screening for the presence of the HLA-B*57:01 allele and the selection of alternative therapies for patients who carry it.

“We have generated abacavir-specific T-cell clones from healthy individuals expressing this allele to study how they are activated,” Bell said. “Our data suggest that both direct and processing-dependent pathways are involved.”

Originally from Lincolnshire, Bell moved to Liverpool in 2005 to embark on her undergraduate studies in pharmacology under the mentorship of Kevin Park and Dean Naisbitt. She is now in her final year of doctoral studies and has used quantitative methodologies, such as mass spectrometry, to study drug metabolism fate in patient immune cells as well as bioinformatic analyses, such as those used to examine human leukocyte antigen haplotype relationships among the alleles associated with organ-specific human diseases.

In France, Tomé won award for work on muscular dystrophy and other triplet repeat expansion disorders

Photo of Stéphanie Tomé 

Stéphanie Tomé, a postdoctoral fellow at the Hospital for Sick Children and the University of Toronto, won the Journal of Biological Chemistry/Herb Tabor Young Investigator Award at the 7th International Conference on Unstable Microsatellites and Human Disease in June in Strasbourg, France.

Tomé was recognized for her work to unravel novel mechanisms and factors that regulate the genetic instability and subsequent pathobiology of the trinucleotide repeat expansion disorder myotonic dystrophy type 1. Also known as Steinert disease, DM1 is the most common adult form of muscular dystrophy and one of more than 40 diseases caused by unstable repeating DNAs.

Tomé earned her doctorate in human genetics in 2009 at Paris Diderot University under the guidance of Geneviève Gourdon. She said she became “fascinated by genetic instability” initially during a stint in 2004 in Stockholm, where she worked with the lab of Ulf Rannug analyzing the instability of CEB1 (human minisatellites) in Swedish people exposed to ionizing radiation. Then she set out on a course “to understand the mechanisms of CAG/CTG repeat instability in DM1 patients using a transgenic mouse model of DM1,” she explained.

She collaborated with Christopher Pearson’s group in Canada, with whom she pursued a postdoc fellowship. She has investigated the role of the DNA mismatch repair proteins MSH2 and MSH3 in the formation of CTG expansions and identified the role of ligase I in the formation of maternal CTG repeat expansion in vivo.

“I participated in the development of an efficient antibody specific to MSH3 with the laboratory of Dr. Glen Morris in the United Kingdom,” she said. “This new tool was important for my subsequent studies and for other labs.”

This semester, Tomé is revisiting her alma mater in Paris to team up with Gourdon again to identify the genetic factors causing repeat contractions, rather than expansions, observed in some patients. She said she is moved by the potential translational impact of their research, adding, “Reversing repeat expansions in the mutant genes to the shorter lengths present in the nondiseased population is a worthy therapeutic goal, as the DNA is a single target that is the basis for the multitude of downstream events and symptoms.”


Photo of Aditi DasAditi Das (addas06@gmail.com) is a Washington, D.C.-based science writer and research consultant at the National Institutes of Health and Maryland Biotech Center. Connect with her on LinkedIn.

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