Studies have linked the serine-threonine kinase MAP4K4 to the regulation of a number of biological processes and/or diseases, including diabetes, cancer, inflammation, and angiogenesis. With a majority of the members of our lead series (e.g., 1) suffering from time-dependent inhibition (TDI) of CYP3A4, we sought design avenues that would eliminate ... More
Deficiency of endothelial sirtuin1 in mice stimulates skeletal muscle insulin sensitivity by modifying the secretome.
Downregulation of endothelial Sirtuin1 (Sirt1) in insulin resistant states contributes to vascular dysfunction. Furthermore, Sirt1 deficiency in skeletal myocytes promotes insulin resistance. Here, we show that deletion of endothelial Sirt1, while impairing endothelial function, paradoxically improves skeletal muscle insulin sensitivity. Compared to wild-type mice, male mice lacking endothelial Sirt1 (E-Sirt1-KO) ... More
Mito-Mendelian interactions alter in vivo glucose metabolism and insulin sensitivity in healthy mice.
JournalAmerican journal of physiology. Endocrinology and metabolism
PubMed ID34370595
The regulation of euglycemia is essential for human health with both chronic hypoglycemia and hyperglycemia having detrimental effects. It is well documented that the incidence of type 2 diabetes increases with age and exhibits racial disparity. Interestingly, mitochondrial DNA (mtDNA) damage also accumulates with age and its sequence varies with ... More
Deciphering the interactome of Ataxin-2 and TDP-43 in iPSC-derived neurons for potential ALS targets.
Ataxin-2 is a protein containing a polyQ extension and intermediate length of polyQ extensions increases the risk of Amyotrophic Lateral Sclerosis (ALS). Down-regulation of Ataxin-2 has been shown to mitigate TDP-43 proteinopathy in ALS models. To identify alternative therapeutic targets that can mitigate TDP-43 toxicity, we examined the interaction between ... More
Quantitative PCR analysis of DNA, RNAs, and proteins in the same single cell.
AuthorsStåhlberg A, Thomsen C, Ruff D, Åman P
JournalClin Chem
PubMed ID23014600
The single cell represents the basic unit of all organisms. Most investigations have been performed on large cell populations, but understanding cell dynamics and heterogeneity requires single-cell analysis. Current methods for single-cell analysis generally can detect only one class of analytes. ... More
The Src inhibitor dasatinib accelerates the differentiation of human bone marrow-derived mesenchymal stromal cells into osteoblasts.
AuthorsId Boufker H, Lagneaux L, Najar M, Piccart M, Ghanem G, Body JJ, Journé F
JournalBMC Cancer
PubMed ID20565769
The proto-oncogene Src is an important non-receptor protein tyrosine kinase involved in signaling pathways that control cell adhesion, growth, migration and differentiation. It negatively regulates osteoblast activity, and, as such, its inhibition is a potential means to prevent bone loss. Dasatinib is a new dual Src/Bcr-Abl tyrosine kinase inhibitor initially ... More