Table of Contents

December 2009; 9 (6)



Nascent Transcripts

Therapeutic Windows

Beyond the Beach

Net Results



  • Cytotoxic-T-lymphocyte- and natural-killer-cell-mediated immune surveillance is crucial for preventing development and growth of malignancies. A recent intriguing study by Rüder et al. demonstrates that the estrogen receptor-binding fragment-associated gene 9 (EBAG9) protein acts as a novel inhibitor of cytotoxic immune responses, potentially influencing growth and spread of malignancies. EBAG9 does this by suppressing production of secretory lysosomes through negative regulation of adaptor proteins involved in intracellular vesicle transfer. Secretory lysosomes contain cell lysis effector molecules released into the immune synapse formed between cytotoxic immune cells and their target tumor cells. Thus, in addition to their direct ER-mediated suppressive effect on estrogen-dependent tumor growth, anti-estrogens may “switch off” EBAG9, thereby bolstering immune cytotoxicity against these cancer cells.

  • Although the influence of neural activity on immune and inflammatory pathways is undisputed, details of how neurotransmitters modulate signaling by cytokine and antigen receptors remain sketchy. New findings on the influence of the serotonin receptor subtype 2A (5-HT2A) and receptors for Tumor Necrosis Factor (TNF) suggest that in some cases there may be direct interactions between neurotransmitter and cytokine receptor signaling. These findings have implications for the many psychiatric patients on medications that modulate serotonin signaling and suggest that neurotransmitter receptors should not be ignored as candidate targets for immunoregulation.


  • Recent advances in high-resolution and high-sensitivity equipment, along with the development of selective biological probes and biomarkers, are rapidly providing new opportunities to investigate drug efficacy and safety. Depending on the modality used, imaging has applications throughout the entire drug lifecycle, and can provide data for target validation, defining mechanism of action, demonstrating efficacy/safety in both preclinical and clinical settings, and applying biomarkers of biological activity. Information gained in these regards can have direct bearing upon the investment of time and resources for phase 2 trials. Imaging studies allow longitudinal measures in the same subject, and recent developments in small-animal scanners can provide translational data for transition from preclinical into early clinical studies. A new wave of neuroimaging studies that engender useful biomarkers of disease for translational research promise to revolutionize the development of therapeutics for a range of neurological diseases.

  • We all know the string of usual suspects: A, T, G, and C. And we’ve known, for some time, that their intimate association with the histones goes much deeper than a mere packaging story: these basic proteins appear to undergo posttranslational modifications that regulate gene activity. Investigators are coming ever closer to understanding exactly how these modifications are being “read” by proteins that—in the case presented here—possess certain zinc fingers (aka PHD fingers). We can now be certain that modifications of specific residues on distinct histones interact with PHD fingers of proteins that in turn recruit additional protein associates to chromatin. The observed complexes can result in specific gene activation or silencing, depending on how the PHD finger–containing proteins “read” the posttranslational cues that reside on histones. In certain instances, mutational alteration of PHD finger–containing proteins has been related to disease; whether new therapeutics can be devised to counter such malfeasance is under ongoing investigation.