Efficient regeneration requires multiple cell types acting in coordination. To better understand the intercellular networks involved and how they change when regeneration fails, we profile the transcriptome of hematopoietic, stromal, myogenic, and endothelial cells over 14 days following acute muscle damage. We generate a time-resolved computational model of interactions and identify VEGFA-driven endothelial engagement as a key differentiating feature in models…
Severely-afflicted COVID-19 patients can exhibit disease manifestations representative of sepsis, including acute respiratory distress syndrome and multiple organ failure. We hypothesized that diagnostic tools used in managing all-cause sepsis, such as clinical criteria, biomarkers, and gene expression signatures, should extend to COVID-19 patients. Here we analyzed the whole blood transcriptome of 124 early (1–5 days post-hospital admission) and late (6–20…
Binding of USF1/2 and TFII-I (RBF-2) at conserved sites flanking the HIV-1 LTR enhancer is essential for reactivation from latency in T cells, with TFII-I knockdown rendering the provirus insensitive to T cell signaling. We identified an interaction of TFII-I with the tripartite motif protein TRIM24, and these factors were found to be constitutively associated with the HIV-1 LTR. Similar to…
Melanoma is a malignant tumor that accounts for the deadliest form of skin cancers. Despite the significant efforts made recently for development of immunotherapeutic strategies including using immune checkpoint inhibitors and cancer vaccines, the clinical outcomes are unsatisfying. Different factors affect efficient cancer immunotherapy such as side-effects, immunosuppressive tumor microenvironment, and tumor heterogeneity. In the past decades, various nanotechnology-based approaches…
The primary focus of Dr. Shernaz Bamji's lab at present is to determine how the addition and removal of a fatty acid lipid molecule, in a process known as ‘protein palmitoylation’, alters the function of key proteins that are involved in signaling at the synapse. They hope to better understand the critical role of palmitoylation in synaptic remodeling, and how disrupted palmitoylation contributes to numerous brain disorders, including Schizophrenia and X-linked intellectual disability.
Spinal cord injury leads to disruption in autonomic control resulting in cardiovascular, bowel, and lower urinary tract dysfunctions, all of which significantly reduce health-related quality of life. Although spinal cord stimulation shows promise for promoting autonomic recovery, the underlying mechanisms are unclear. Based on current preclinical and clinical evidence, this narrative review provides the most plausible mechanisms underlying the effects…
Massively parallel DNA sequencing has led to the rapid growth of highly multiplexed experiments in biology. These experiments produce unique sequencing results that require specific analysis pipelines to decode highly structured reads. However, no versatile framework that interprets sequencing reads to extract their encoded information for downstream biological analysis has been developed. Here, we report INTERSTELLAR (interpretation, scalable transformation, and…
Dr. Natalie Strynadka's team focuses on atomic resolution characterization and analysis of microbial targets, often membrane protein assemblies, that mediate drug resistance or are potential new targets for structure-guided antibiotic design. They used cryogenic electron microscopy to characterize the first atomic structures of a novel receptor that senses beta-lactam antibiotics in the environment, then signals through the membrane to control (via unprecedented direct proteolysis of a repressor), expression of genes underlying broad spectrum beta-lactam antibiotic resistance in drug resistant Staph aureus strains.
Novel therapeutics to manage bacterial infections are urgently needed as the impact and prevalence of antimicrobial resistance (AMR) grows. Antivirulence therapeutics are an alternative approach to antibiotics that aim to attenuate virulence rather than target bacterial essential functions, while minimizing microbiota perturbation and the risk of AMR development. Beyond known virulence factors, pathogen-associated genes (PAGs; genes found only in pathogens…