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...
For some inducible genes, the rate and molecular mechanism of transcriptional activation depend on the prior experiences of the cell. This phenomenon, called epigenetic transcriptional memory, accelerates reactivation, and requires both changes in chromatin structure and recruitment of poised RNA polymerase II (RNAPII) to the promoter. A well-established model for...
Ensuring adequate water quality is essential for human health and for effective allocation of resources in agriculture, energy, and manufacturing. However, the current state-of-the-art for water quality testing requires expensive equipment and technical expertise to analyze samples and takes days to obtain results from off-site labs, making it inaccessible to...
SAMDI-MS, which stands for self-assembled monolayers (SAMs) for matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS), is a powerful tool that has enabled the development of novel high-throughput screening and experimentation methods for decades. SAMDI-MS works by immobilizing analytes to functionalized SAMs prior to MS analysis and is capable of...
Reproduction requires a complex orchestration of processes from the formation of the reproductive system through the successful development of the fetus, and nutrients are necessary to fuel these processes during many aspects of reproduction. Zinc is an essential metal that is fundamental in gamete maturation, gonadogenesis, and fertilization. Disruption in...
Methanotrophs, bacteria that can metabolize methane, remain a promising solution to mitigating the effects of climate change by removing atmospheric methane and converting it to useful chemical precursors. However, a full understanding of the main enzyme they use to oxidize methane, particulate methane monooxygenase (pMMO), is critical for harnessing their...
MYC regulates multiple gene programs, raising questions about the potential selectivity and downstream transcriptional consequences of MYC inhibitors as cancer therapeutics. MYC func-tions to either globally amplify RNA production or selectively regulates genes by repression or ac-tivation. In models of MYC inhibition by small molecules the functionality of MYC is...
DNA double-strand breaks (DSBs) are caused by either endogenous agents or exogenous ionizing radiation and chemicals. Incorrect DSB repair can lead to undesired genome rearrangements. Homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways are two major DNA repair pathways that repair DSBs and maintain genome integrity. When homologous DNA is...
CD99-Like 2 (CD99L2) is a 52 kDa type I glycoprotein expressed on leukocytes and endothelial cells as well as other cell types in mice. It is related to CD99, although it shows only 32% sequence identity. CD99L2 has been shown to play a role in leukocyte extravasation in mice under...
Glioblastoma multiforme (GBM) is the most prevalent primary central nervous system tumor, characterized by resistance to therapeutic intervention, inevitable recurrence, and ultimately patient death. The dismal prognosis is due in part to underlying molecular factors that promote an intratumoral cellular state heterogeneity and protect tumor cells from cell death pathways....
RNA viruses cause a wide range of diseases that range from mild respiratory illness to fatal hemorrhagic fevers. To combat these pathogens, most cells in the human body scan the cell for viruses and activate a potent cell-intrinsic immune response by producing interferon (IFN), a cytokine that amplifies the innate...