Neuroleadership: a new way for happiness management.

In a post-pandemic era, managers and leaders have a role to enable the changes needed to make workplaces happier and more productive. This paper aims to analyse the role of neuroleadership in the application of happiness management. Two research questions are proposed: what do we know about neuroleadership? and what role can neuroleadership play in happiness management? A mixed methodology is applied. A bibliometric technique is used to identify the main topics studied in neuroleadership. An in-depth analysis and logical reasoning are applied to propose a neuroleadership research roadmap and to present some research pathways for neuroleadership for happiness management. A neuroleadership research roadmap is proposed, considering the approaches, practices/actions, and purposes. It is observed that the consideration of the management of emotions and cognitive processes in the work environment is attracting interest to develop a leadership focused on making better workplaces. A new line of action focused on the management of happiness is emerging. In addition, neuroleadership is presented as a new way of understanding management. Their combined application can mark a before and after in business management, and for that, a proposal of future research lines and questions is developed. This paper presents four future research pathways-perspectives, reasons, adoption and implementation, and results-for studying neuroleadership for happiness management.

Direct Measurement of KDM1A Target Engagement Using Chemoprobe-based Immunoassays.

The assessment of the target engagement, defined as the interaction of a drug with the protein it was designed for, is a basic requirement for the interpretation of the biological activity of any compound in drug development or in basic research projects. In epigenetics, target engagement is most often assessed by the analysis of proxy markers instead of measuring the union of the compound to the target. Downstream biological readouts that have been analyzed include the histone mark modulation or gene expression changes. KDM1A is a lysine demethylase that removes methyl groups from mono- and dimethylated H3K4, a modification associated with the silencing of gene expression. Modulation of the proxy markers is dependent on the cell type and function of the genetic make-up of the cells investigated, which can make interpretation and cross-case comparison quite difficult. To circumvent these problems, a versatile protocol is presented to assess the dose effects and dynamics of the direct KDM1A target engagement. The assay described makes use of a KDM1A chemoprobe to capture and quantify uninhibited enzyme, can be broadly applied to cells or tissue samples without the need for genetic modification, has an excellent window of detection, and can be used both for basic research and analysis of clinical samples.

Chemoprobe-based assays of histone lysine demethylase 1A target occupation enable in vivo pharmacokinetics and pharmacodynamics studies of KDM1A inhibitors.

Screening of cellular activity for inhibitors of histone lysine modifiers is most frequently performed indirectly by analyzing changes in the total levels of histone marks targeted by lysine methylases/demethylases. However, inhibition of histone lysine modifiers often leads to local rather than total changes in histone marks. Also, because histone modifications can be modulated by more than one cellular enzyme, it is not always clear whether changes in histone marks are a direct or indirect consequence of the inhibitor treatment applied. Direct assessment of target occupation can provide a useful tool to quantify the fraction of an epigenetic modifier that is bound to a pharmacological inhibitor (target engagement). Here, we developed and used a novel chemoprobe-based immunoassay to quantify target engagement in cells. Quantification of the fraction of free KDM1A was made possible, in an immune-based assay, by coupling a biotinylated chemoprobe to a warhead capable of selectively and irreversibly binding to the free active form of KDM1A. The results obtained confirmed that this approach is able to determine the degree of target engagement in a dose-dependent manner. Furthermore, the assay can be also used on tissue extracts to analyze the in vivo pharmacokinetics and pharmacodynamics relationship of KDM1A inhibitors, as has been exemplified with ORY-1001 (iadademstat), a potent and irreversible inhibitor of KDM1A. The principle of this assay may be applied to other targets, and the KDM1A probe may be employed in chemoproteomic analyses.