In this video collection, authors of findings published in The Journal of Clinical Investigation present personally guided tours of their results. The JCI accepts video submissions from authors of recently accepted manuscripts. Instructions can be found on the Author's Take Guidelines page.
The hormone kisspeptin is essential for reproductive function, an effect that is mediated by its actions in the hypothalamus. Recent studies suggest that kisspeptin and its receptor are also expressed in other regions of the brain; however, little is known about the effects of this hormone in the brain in regions outside of the hypothalamus. In this episode, Waljit Dhillo and colleagues evaluate limbic system-specific effects of kisspeptin administration in healthy male volunteers. The data from this study indicate that kisspeptin action in the limbic system mediates sexual and emotional brain processing.
Retinitis pigmentosa (RP) is a heterogeneous genetic disorder that is characterized by a progressive loss of photoreceptors that results in deterioration of vision. While gene therapy has shown promise for some forms of RP, over 60 genes have been implicated in this disorder; therefore, non-gene-targeted therapies are of great interest. In this episode, Stephen Tsang and colleagues discuss their study, which shows that upregulation of glycolytic flux, via targeted downregulation of sirtuin 6, in rod photoreceptors improves photoreceptor survival and preserves vision in a mouse model of RP. As this strategy is not gene-specific, it may be beneficial for a range of neurodegenerative disorders.
Cancer cells have a different response to nutrient limitation than healthy cells; therefore, targeting nutrient acquisition pathways has potential as a therapeutic strategy for limiting cancer cell growth. In this episode, Aimee Edinger discusses a recent study from her group, which describes the effects of a sphingolipid-based compound, SH-BC-893, in multiple pre-clinical cancer models. SH-BC-893 simultaneously disrupts both glucose and amino acid transporters and was effective against both rapid- and slow-growing tumors without affecting normal tissues. The results of this study support further exploration of the therapeutic potential of this compound.
There is substantial crosstalk between tumor cells and surrounding stromal cell populations, and the specific microenvironment of a tumor greatly influences progression, malignancy, metastasis, plasticity, and therapeutic response. In this episode, Michael Stürzl, Elisabeth Naschberger, and Andrea Liebl discuss their study, which identifies endothelial cell secretion of the protein SPARCL1 as an important regulator of colorectal cancer aggressiveness. SPARCL1 expression was increased in endothelial cells from normal colon and in tumor endothelial cells that were isolated from patients with a favorable prognosis and dramatically reduced in tumor endothelial cells from patients with aggressive colorectal carcinoma. Together, the results of this study indicate that endothelial cell-derived SPARCL1 promotes an antitumorigenic microenvironment by inducing cell quiescence and limiting angiogenesis.
Pulmonary hypertension (PH) refers to a collection of vascular diseases that are characterized by increased arterial pressure in the lung, which can subsequently lead to heart failure and possibly death. It is not clear how PH develops or how early events in the disease correlate with later phenotypes. In this episode, Stephen Chan discusses work from his laboratory that links increased vascular stiffness to altered glutamine metabolism in the pathogenesis of PH. The results of this study provide important insight into the development of PH and identify metabolic pathways that have potential as therapeutic targets for PH.