Posts By: Nicola Brunetti-Pierri

Vascularized and functional human liver was generated from transplantation of an iPSC-derived organ bud

Posted by & filed under Part 02: PERSPECTIVES.

The first demonstrating of a functional human organ (i.e. liver) generated from pluripotent stem cells has been recently reported in Nature. Specified hepatic cells (immature endodermal cells destined to track the hepatic cell fate), endothelial cells and mesenchymal cells self-organized into three-dimensional liver buds in vitro that were transplanted in recipient mice. The vasculature of liver bud transplants became functional […]

Loss of function mutations in SIM1 are responsible for severe obesity and Prader-Willi-like syndrome

Posted by & filed under Part 18: HORMONES.

Two independent groups have published on the July issue of the Journal of Clinical Investigation that loss of function mutations in the SIM1 gene result in severe obesity and in a Prader-Willi-like phenotype. SIM1 is a basic helix-loop-helix transcription factor involved in the development and function of the paraventricular nucleus of the hypothalamus. SIM1 haploinsufficiency in […]

WNT1 mutations are responsible for early-onset osteoporosis and osteogenesis imperfecta

Posted by & filed under Part 22: CONNECTIVE TISSUE.

Three independent studies have shown that WNT1 mutations are responsible for bone fragility. WNT1 mutations were found in families with moderately severe recessive osteogenesis imperfecta and early-onset osteoporosis. WNT1 is a secreted signaling protein that binds the frizzled receptor (FZD) and the co-receptor low-density lipoprotein-receptor-related protein 5 (LRP5). Biallelic loss-of-function mutations in LRP5 result in recessive […]

Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs

Posted by & filed under Part 21: MEMBRANE TRANSPORT DISORDERS.

The group of Michael Welsh has recently published a paper showing that CFTR expression in the intestine is sufficient to rescue meconium ileus in cystic fibrosis (CF) pigs. CF pigs develop disease with features remarkably similar to those of CF patients, including exocrine pancreatic destruction, focal biliary cirrhosis, micro-gallbladder, vas deferens loss, airway disease, and meconium ileus. Whereas […]

Bioengineered sulphamidase for therapy of MPS IIIA

Posted by & filed under Part 16: LYSOSOMAL DISORDERS.

A paper recently published in EMBO Molecular Medicine by Sorrentino et al. showed efficacy of a chimeric sulphamidase that was engineered by adding the signal peptide from the highly secreted iduronate-2-sulphatase and the blood-brain barrier (BBB)-binding domain from the Apolipoprotein B. This bioengineered sulphamidase was highly secreted, was efficient in BBB transcytosis, restored enzyme activity in the brain, improved […]

Loss of SNX27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down syndrome

Posted by & filed under Part 05: CHROMOSOMES.

A recent paper in Nature Medicine showed that Down syndrome brains have reduced expression of Sorting nexin 27 (SNX27) and CCAAT/enhancer binding protein beta (C/EBP beta) and identified C/EBP beta as a transcription factor for SNX27. Down syndrome results in overexpression of miR-155, a chromosome 21–encoded microRNA that negatively regulates C/EBP beta, thereby reducing SNX27 expression. SNX27 is a brain-enriched […]

Phenylbutyrate for therapy of pyruvate dehydrogenase deficiency

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION.

My apologies for posting my own work published this month in Science Translational Medicine. The data presented in this paper highlight the potential of phenylbutyrate for therapy of pyruvate dehydrogenase complex (PDHC) deficiency, the most common genetic disorder leading to lactic acidosis, and systemic lactic acidosis. PDHC activity is regulated by phosphorylation of the E1-alpha subunit by pyruvate […]

Discovery of a long noncoding transcript coating the active X chromosome

Posted by & filed under Part 05: CHROMOSOMES.

X-chromosome inactivation (XCI) in mammals relies on XIST, a long noncoding transcript that coats and silences the X chromosome in cis.  Vallot et al. have discovered a long noncoding RNA, XACT, that is expressed from and coats the active X chromosome in human pluripotent cells. In the absence of XIST, XACT is expressed from both X […]

FGF21, a mitochondrial disease biomarker, extends lifespan in mice

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION.

Measurement of Fibroblast growth factor 21 (FGF21) concentrations are raised in serum of mice and humans with mitochondrial respiratory chain deficiencies and has been proposed by Suomalainen et al. ( as a first-line diagnostic test for mitochondrial disorders to reduce the need for muscle biopsy. FGF21 is a hormone secreted by the liver during fasting […]

Novel therapeutic targets for malignant peripheral nerve sheath tumors

Posted by & filed under Part 04: CANCER.

A recent paper in the Journal of Clinical Investigation identified targets for therapy of malignant peripheral nerve sheath tumors (MPNST) in patients with Neurofibromatosis type 1 (NF1). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras/Raf/MEK/ERK signaling. PD0325901, a highly selective pharmacological inhibitor of MEK, reduced aberrantly […]