Three new JBC-Herb Tabor Young Investigator Award winners

Andrew DeVilbiss

Andrew DeVilbiss, a doctoral student in the cellular and molecular pathology graduate program at the University of Wisconsin School of Medicine and Public Health, received a Journal of Biological Chemistry/Herbert Tabor Young Investigator Award for his work on transcriptional control of erythropoiesis, the development of red blood cells.
 
Many changes must occur for a hematopoietic stem cell to become a red blood cell, including removal of the nucleus, alterations to the cytoskeleton and changes in the expression level of the globin genes, heme biosynthesis genes and many other genes. The master agent of this change is the transcription factor GATA-1.
 
ASBMB News Pic: Tabor DeVilbiss;
Andrew DeVilbiss received his Tabor award at the Midwest
Chromatin and Epigenetics meeting in Madison, Wis., in
May. JBC Associate Editor John Denu of the University
of Wisconsin-Madison issued the award.
DeVilbiss described a new interaction between the transcription factor and a chromatin-modifying enzyme with the exciting additional discovery that the interaction was context-dependent. That is, GATA-1 required the chromatin-modifying enzyme to repress some but not all of its target genes.
 
Moreover, the effects of the chromatin-modifying enzyme in combination with other known regulators of GATA function were variable: Some of the shared target genes also were sensitive to a second and/or third coregulator, while others were not.
 
It previously had been thought that GATA factors mediate transcription using a common cohort of coregulators at the majority of target genes. However, DeVilbiss and his coworkers found a more intricate mechanism whereby transcriptional repression by GATA-1 is dependent on different combinations of coregulators at different target genes.
 
Of his future work, DeVilbiss says, “I am now interested in identifying the unique molecular attributes of (GATA-1 regulated) loci that mandate different coregulator requirements for repression.”

Sheila Sadeghi

Sheila Sadeghi  
Sheila Sadeghi received her Tabor award at the 20th International Symposium on Microsomes and Drug Oxidations in Stuttgart, Germany. JBC Associate Editor F. Peter Guengerich of Vanderbilt University issued the award.
Sheila Sadeghi, a lecturer at the University of Torino in Italy, was honored with a Tabor award for her work on developing a testing platform for toxic interactions between small molecules that are known to be safe when administered individually.
 
Predicting adverse interactions between drugs is difficult; screening all possible combinations in model organisms would be prohibitively expensive and time-consuming. However, one major known source of toxicity is inhibition of the liver enzyme cytochrome P450, which catalyzes the metabolism and clearance of many drugs.
 
Because P450 is a redox enzyme, its activity is difficult to study outside of its complex biochemical context; however, Sadeghi and her colleagues used a solid electrode surface to immobilize P450 and characterize its catalytic rate in the presence of individual or combinations of drugs. This technology gives a way to predict exactly how two drugs metabolized by P450 will interact with one another and prevent patients from being prescribed deadly combinations.
 
In the long term, Sadeghi envisions her work leading to high-throughput tests of drug–drug and food–drug interactions and also applications that may use polymorphic P450 variants better to individualize treatment regimens.

Gopal Gunanathan Jayaraj

Gopal Gunanathan Jayaraj, a doctoral student at the CSIR-Institute of Genomics and Integrative Biology in India, received a Tabor award for his work illuminating the reasons that aminoglycoside antibiotics, such as the tuberculosis drug streptomycin, occasionally damage patients’ hearing for life.
 
Gopal Gunanathan Jayaraj
Gopal Gunanathan Jayaraj received his Tabor award at the International Conference on Chemical Biology – Disease Mechanisms and Therapeutics in Hyderabad in February. JBC Associate Editor Ruma Banerjee of the University of Michigan issued the award.
Jayaraj was studying a previously described effect of streptomycin on microRNAs, a category of small, noncoding RNAs that affect the translation of specific target genes. His colleagues had shown that streptomycin could bind to pre-microRNA21, preventing the microRNA from being completely processed and affecting cells’ ability to express microRNA21 targets.
 
When he followed up with a microRNA-wide screen to determine whether this effect extended beyond miRNA21, Jayaraj found that a large cluster of hearing-related microRNAs also was affected. Jayaraj characterized these interactions biochemically and further showed that streptomycin could repress these microRNAs in a zebrafish system in vivo, offering a tantalizing, though partial, possible explanation for the antibiotic’s toxic side effects.
 
Jayaraj adds that “this study also warrants a cautionary re-evaluation of other RNA-binding drugs for their off-target effects in the context of miRNA and other functional noncoding RNA.”
 
To learn more about the JBC/Herb Tabor Young Investigator award program, visit http://www.jbc.org/site/home/tabor_award.
Laurel OldachLaurel Oldach (loldach1@jhmi.edu) earned a B.A. in biology from Reed College and is pursuing a Ph.D. in biological chemistry at Johns Hopkins University School of Medicine.