Erythropoietin-producing human hepatocellular (Eph) receptors and their corresponding ephrin ligands are asymmetrically expressed at cell-cell contacts allowing for bidirectional signaling with forward signaling through the receptor expressing cell and reverse signaling through the ligand expressing cell. Eph receptors are the largest family of receptor tyrosine kinases (RTKs) in mammals, which...
Over the past decade significant advancements have been made across the field of cancer biology resulting in transformative new therapies. Despite these advancements, treatments for metastatic cancer remain relatively ineffective. Metastasis is coordinated by various types of “healthy†stromal cells in addition to the tumor cells themselves. This requires a...
Ubiquitous in the environment are bacteria that have evolved to adapt to the environmental niches they colonize. To this end, bacteria sensory and signaling molecules are required for processing these extracellular changes within their environment into changes in gene expression. The plague-causing pathogen, Yersinia pestis, contains a repertoire of two-component...
In 2015, the United States Department of Agriculture (USDA) reported that 1 in 6 Americans fall ill with a foodborne infection annually, resulting in more than 3000 fatalities and an estimated $15 billion in economic burden due to combined medical costs, productivity loss, and death. On a per-case basis, infections...
Herpesvirus virions consist of three layers: nucleocapsid, tegument, and envelope. The innermost layer, the nucleocapsid, initially assembles as an immature procapsid precursor built around viral scaffold proteins. The event that initiates procapsid maturation is unknown but it is dependent upon activation of the internal protease. Scaffold cleavage triggers angularization, or...
Platyrrhines are an enigmatic and intriguing radiation of New World monkeys that currently inhabit the western hemisphere from Argentina to Mexico. Platyrrhini, a taxonomic parvorder within Primates, is their formal taxonomic designation, as they represent the sister group of the Catarrhini or all of the Old World monkeys and apes....
Immune checkpoint inhibitors have not been effective for immunologically “cold” tumors, such as prostate cancer, which contain scarce tumor infiltrating lymphocytes. We hypothesized that select tissue-specific and immunostimulatory bacteria can potentiate these immunotherapies. Here we show that a patient-derived prostate-specific microbe, CP1, in combination with anti-PD-1 immunotherapy, increased survival and...
There is a shortage of research models that adequately represent the unique mucosal environment of human ectocervical tissue, which has limited the development of new therapies for treating infection or cancer. I hypothesized that engineering the microenvironment of ectocervical tissue with in vivo-like endocrine and paracrine support, would enable squamous...
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting approximately 1 in 10 reproductive-age women and remains the leading cause of female factor infertility among women of childbearing age. PCOS presents with features of hyperandrogenism, irregular menses and polycystic ovaries. Twin and family studies have demonstrated high heritability estimates...
Post-transcriptional gene silencing (PTGS) and, more specifically, RNA interference (RNAi) include the processes by which a small double-stranded RNA, 19 to 22 nucleotides (nts) long, negatively regulates the expression and/or translatability of a target RNA, which harbors reverse complementarity to that small RNA, by recruiting the so-called RNA-Induced Silencing Complex...
Pseudomonas aeruginosa is a Gram-negative pathogen that frequently causes severe nosocomial infections through expression of virulence factors, evasion of immune clearance and resistance to therapeutic antimicrobial agents. These factors have led the US Centers for Disease Control and Prevention (CDC) and Infectious Disease Society of America (IDSA) to identify P....
Transcription by RNA polymerase II (Pol II) in metazoans is regulated in multiple steps, including preinitiation complex (PIC) formation, initiation, Pol II escape, productive elongation, cotranscriptional RNA processing, and termination. Genome-wide studies have demonstrated that the phenomenon of promoter-bound Pol II pausing is widespread, especially for genes that respond to...
Mucolipins are lysosomal cation channels, with high permeability to calcium ions, that are thought to regulate endolysosomal trafficking. While mucolipin 1 is expressed in all cells, mucolipin 3 is expressed in a small subset of cells (i.e. neonatal intestinal enterocytes, cochlear hair cells and marginal cells of stria vascularis). This...
Spinal cord injury occurs with a worldwide incidence of 13-33 cases per million per year, and more than 2.5 million patients worldwide suffer from spinal cord injury (SCI)-related disability (1, 2). Different methods have been attempted to promote axonal regeneration, including neurotrophin injection, hydrogel injection, olfactory ensheathing cells implantation and...
X-ray Fluorescence Microscopy (XFM) is a useful technique for study of biological samples. XFM was used to map and quantify endogenous biological elements as well as exogenous materials in biological samples, such as the distribution of titanium dioxide (TiO2) nanoparticles. TiO2 nanoparticles are produced for many different purposes, including development...
Eosinophils are major effector cells in diseases including asthma, rhinitis, certain gastrointestinal disorders and atopic dermatitis. Current treatments include mediator antagonists and anti-inflammatory drugs that reduce allergic cell numbers and inhibit mediator release, but they are not fully effective or curative. On their surface, eosinophils selectively express Siglec-8 (sialic acid-binding...
The Bcl-2 family is considered the guardian of the mitochondrial apoptotic pathway. While there are numerous endogenous Bcl-2 antagonists that share similar homology, structure, topology, and expression pattern, only the loss of Bim in mice is sufficient to lead to the development of a systemic autoimmunity. Even loss of both...
The Pseudomonas aeruginosa type III secretion system delivers effector proteins directly into target cells, allowing the bacterium to modulate host cell functions. ExoU is the most cytotoxic of the known effector proteins and has been associated with more severe infections in humans. Previous studies have shown that ExoU is a...
The study of tumor metabolism from the middle of the 20th century through the early 21st almost entirely ignored the mitochondria; instead, the field focused on cancer cells use of glycolysis even when oxygen was not limiting, termed aerobic glycolysis. Due to this observation, it was often speculated that malignant...
MAPK-interacting kinase (MNK) signaling leads to activation of cap-dependent mRNA translation through phosphorylation of the eukaryotic translation initiation factor 4E (eIF4E). In cancer cells, MNK-eIF4E signaling promotes translation of oncogenic mRNAs. In glioblastoma (GBM), the deadliest malignant brain tumor, MNK-eIF4E signaling is aberrantly activated and represents a promising therapeutic target....