Pollution-intensive industrial manufacturing processes threaten the health of ecosystems and societies through toxic waste streams and energy intensive processes that lead to greenhouse gas emissions. Biological systems present more sustainable routes to many useful industrial chemicals by using enzymes at low temperatures, but the time and effort required to optimized...
Genetic studies have found variants in the protein-degrading autophagy-lysosomal pathway (ALP) to be among the most common risk factors for developing Parkinson’s disease (PD). Macroautophagy (MA) is the arm of this pathway which delivers cytosolic components to lysosomes for degradation and is essential for neuronal health. The defining pathological protein...
SCN2A encodes the NaV1.2 voltage-gated sodium channel, which is thought to contribute to the development of the central nervous system. Pathogenic variants in SCN2A have been associated with neurodevelopmental disorders (NDD), including developmental and epileptic encephalopathies (DEE), intellectual disability (ID), and autism spectrum disorder (ASD). These disorders represent a significant...
Pediatric high-grade gliomas (pHGGs) are aggressive pediatric CNS tumors and an important subset are characterized by mutations in H3F3A, the gene that encodes Histone H3.3 (H3.3). Substitution of Glycine at position 34 of H3.3 with either Arginine or Valine (H3.3G34R/V), was recently described and characterized in a large cohort...
Autism spectrum disorder (ASD) and intellectual disability (ID) are two of the most highly prevalent neurodevelopmental disorders (NDDs), each affecting roughly 2% of the population. Despite the need for therapies, few exist due to a myriad of challenges, such as the complex underlying genetic etiology and historic inaccessibility of neural...
CD95/Fas ligand (CD95L) is a well characterized activator of extrinsic apoptosis. CD95L protein binds to its cognate receptor, CD95/Fas/APO-1, inducing apoptotic signaling in sensitive cells. However, expression of CD95L is toxic even in the absence of CD95. We previously reported that the CD95L open reading frame (ORF) is enriched for...
CD95/Fas ligand (CD95L) is a well characterized activator of extrinsic apoptosis. CD95L protein binds to its cognate receptor, CD95/Fas/APO-1, inducing apoptotic signaling in sensitive cells. However, expression of CD95L is toxic even in the absence of CD95. We previously reported that the CD95L open reading frame (ORF) is enriched for...
Tumor-initiating cells with reprogramming plasticity are thought to be essential for cancer development and metastatic regeneration in many cancers; however, the molecular mechanisms are not fully understood. We have previously identified that CD44, a breast tumor-initiating cell marker, drives mammosphere self-renewal and multicellular aggregation of circulating tumor cell (CTC) clusters,...
The ability to regenerate lost tissues or organs is widespread in the animal kingdom, but the mechanistic basis underpinning this process is incompletely understood. The planarian flatworm Schmidtea mediterranea has an incredibly robust and flexible capacity for regeneration, able to regenerate an entire organism from arbitrary starting points. This makes...
Genetic variation in genes regulating metabolism may be advantageous in some settings but not others. The non-failing adult heart relies heavily on fatty acids as a fuel substrate and source of ATP. In contrast, the failing heart favors glucose as a fuel source. A bootstrap analysis for genes with deviant...