Articles in 2013

Autoimmunity is triggered by trafficking of self-reactive T cells into tissues. Joonsoo Kang and colleagues show that the kinase ITK regulates T cell trafficking. ITK inhibition or genetic ablation prevents homing of autoreactive T cells into tissues and reduces islet destruction in models of type 1 diabetes without affecting T cell activation or antiviral T cell responses, suggesting that this kinase may be targeted in autoimmune disease.

T cells specific for hepatitis C virus (HCV) have been reported in some individuals who have been repeatedly exposed to virus, yet have never had detectable HCV or HCV-specific antibodies. These findings suggest that T cells in these individuals may protect against infection by HCV. Barbara Rehermann and colleagues now test this assumption in a nonhuman primate study exposing animals to a very low dose of HCV.

Matthias Hackl and his colleagues developed a new serial multiphoton microscopy approach to track migrating podocytes and parietal epithelial cells over time in vivo in the intact kidney. Use of this new approach is demonstrated in several mouse models and should help answer questions surrounding podocyte proliferation and migration to other (peri)glomerular regions, thus shedding light on the mechanisms of glomerular injury and regeneration.

Detecting tumor recurrences early and developing therapies capable of targeting recurrences that resist frontline therapy could be of enormous benefit to patients with cancer. Using mouse tumor models, Richard Vile and colleagues find a cytokine signature associated with very early stage recurrences, as well as evidence that the recurrent tumors are resistant to innate immune responses. By targeting the altered phenotype of the recurrent tumors, the researchers cured the mice of cancer, suggesting new avenues for research into human cancer recurrence.

Excess ammonia in the blood can cause neurologic dysfunction and seizures. Although previous studies have suggested astrocyte swelling and brain edema are associated with hyperammonemia, the authors show that ammonia compromises potassium buffering by astrocytes, increasing extracellular potassium concentrations and resulting in cortical disinhibition. Pharmacological or genetic inhibition of NKCC1 attenuates ammonia-induced neurologic impairment and seizures, suggesting hyperammonemia may be treated by targeting NKCC1.

Dean Sheppard and his colleagues show that genetic or pharmacological inhibition of α_v integrin signaling ameliorates fibrosis in several solid organs.

In exploring the possibility that racial differences in platelet function might exist, Paul Bray and his colleagues report that platelets from blacks have a greater propensity to aggregate than those from whites in response to activation of the PAR4 thrombin receptor. Mechanistically, this difference in platelet function seems to reflect differences in the expression of the microRNA miR-376c and its target, the enzyme phosphatidylcholine transfer protein.

University technology transfer offices are tasked with helping bring the inventions made by academics to the attention of potential investors. But selling off intellectual property to patent aggregators in an effort to bring in money to their institutions could stifle the future development of new technologies.

In August, Novartis appointed Ricardo Dolmetsch to be the company's global head of neurosciences—the first new hire for its reincarnated neuroscience division. As a professor at California's Stanford University School of Medicine for the past ten years, Dolmetsch made his name using induced pluripotent stem (iPS) cells to study a rare form of autism known as Timothy syndrome. Elie Dolgin met with Dolmetsch at the Novartis Institutes for BioMedical Research in the Technology Square area of Cambridge to discuss how he plans to succeed where so many others have failed.

Understanding the molecular mechanisms that govern diabetes-induced loss of kidney function is crucial. A new study shows that in mouse models of diabetes, sirtuin 1 (Sirt1) in the proximal tubules of the kidney can modulate the expression of podocyte Claudin-1, a key regulator of albuminuria and glomerular function (pages 1496–1504).