Living fabrication of functional semi-interpenetrating polymeric materials
Xiling Shen was part of a team that created a new approach to fabricate semi-interpenetrating polymer networks (IPN) that is living, functional and biocompatible. This is the first time bacterially-fabricated living materials have been used in a setting with direct clinical relelvance: to protect the gut microbiota against unintended perturbations by antibiotics.
Characterization of liver GSD IX γ2 pathophysiology in a novel Phkg2−/− mouse model
Aravind Asokan was part of a team that made the first mouse model that can recapitulate the liver-specific pathology of patients with Liver Glycogen Storage Disease IX.
Three-dimensional tissue-engineered human skeletal muscle model of Pompe disease
Nenad Bursac and team developed a 3-D model of infantile-onset Pompe disease that demonstrates the signature pathological features of the disease.
The NIH Somatic Cell Genome Editing program
Charlie Gersbach, Nenad Bursac and Aravind Asokan are part of the NIH Somatic Cell Gene Editing Consortium. In this publication, the team lays our their plans to develop and benchmark approaches to induce and measure genome modifications, and define downstream functional consequences of genome editing within human cells.
In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration
Ken Poss and team used a transgenic BioID2 strategy to capture cell-specific proteome changes in cardiomyocytes during heart regeneration in adult zebrafish.
Correcting signal biases and detecting regulatory elements in STARR-seq data
Bill Majoros, Andrew Allen, Tim Reddy and team developed a statistical model that corrects technical biases in STARR-seq data and improves detection of regulatory elements.
AP-1 subunits converge promiscuously at enhancers to potentiate transcription
Charlie Gersbach, Tim Reddy and team definitively established the genome-wide binding patterns of five AP-1 subunits using CRISPR to introduce a common antibody tag on each subunit.
Mutational processes in cancer preferentially affect binding of particular transcription factors
Raluca Gordan collaborated with Duke-NUS to develop the "Signature-QBiC" model that integrates signature profiles of mutational processes with the QBiC estimates of changes in binding affinity to investigate the effect of mutational signatures on the binding of 582 human transcription factors.
Adeno-Associated Virus-Mediated Gene Therapy in the Mashlool, Atp1a3 Mashl/+, Mouse Model of Alternating Hemiplegia of Childhood
Boris Kantor and Aravid Asokan were part of a team that investigated the effects of delivering an extra copy of the normal gene in a mouse model carrying the most common mutation that causes Alternating Hemiplegia of Childhood (AHC) in humans. AHC is a devastating autosomal dominant that can cause evere hemiplegia and dystonia spells, ataxia, debilitating disabilities, and premature death.
Exercise mimetics and JAK inhibition attenuate IFN-γ–induced wasting in engineered human skeletal muscle
Nenad Bursac and team demonstrated that human muscle has an innate ability to ward off the damaging effects of chronic inflammation when exercised. The discovery was made possible through the use of lab-grown, engineered human muscle.
Causal network inference from gene transcriptional time-series response to glucocorticoids
Tim Reddy and team developed a new method, BETS, that infers causal gene networks from gene expression time series. BETS runs quickly because it is parallelized, allowing even data sets with thousands of genes to be analyzed.
Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity
Xiling Shen was part of a team that provided evidence linking recent advances in stem cell biology with intestinal development to reprogram colonic fibroblasts isolated from ulcerative colitis patients to induced pluripotent stem cells, followed by directed differentiation to induced human ulcerative colitis organoids. This patient-derived organoid model will generate new insights into the underlying pathogenesis of ulcerative colitis while offering opportunities to tailor interventions to the individual patient.
Control of osteoblast regeneration by a train of Erk activity waves
Ken Poss and team applied transgenic tools, live imaging, quantitative analysis and mathematical modelling to investigate how signalling dynamics regulate bone regeneration in adult zebrafish. They discovered a signaling protein molecules called Erks that cause cells to divide also tell them when to stop dividing. This discovery could have future implications for regenerative therapy in humans.