In this dissertation I study evolutionary patterns at genes encoding antimicrobial peptides (AMPs) in frogs. AMPs are short, amphipathic, cationic, secreted proteins that kill bacteria and other pathogens through a non-catalytic mechanism that involves
binding to and disrupting the microbial cell membrane. In many animal taxa, positive selection is much...
Otoferlin is a C2-domain, transmembrane protein whose mutated form is responsible for the DFNB9 subtype of prelingual hearing impairment. Mutations in otoferlin cause an autosomal recessive, non-syndromic form of deafness that is characterized by auditory neuropathy/ auditory dissynchrony (AN/AD), meaning that the outer hair cells (OHCs) are normal, and the...
Cognitive impairment, or cognitive decline, a noticeable and measurable decline in cognitive abilities (e.g. memory and learning) that exceeds those attributed to normal aging, represents an early symptom of neurodegeneration and increased risk for progression to more severe dementias, such as Alzheimer's disease (AD). While the complex etiology of these...
Coibamide A is a methyl-stabilized cyclic depsipeptide with a lariat side chain that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups program based in Panama. Previous testing of this potent and selective growth-inhibitory agent in the National Cancer Institute (NCI) in vitro 60 human...
Auditory defects and disorders are prevalent at all ages and affect 8% of the population in developed nations including newborns and children. Congenital hearing loss is the most common birth defect and it is estimated that 1 in 1000 children are affected by deafness at birth or before the onset...
Circadian clocks are endogenous molecular mechanisms that coordinate daily rhythms in gene expression, cellular activities, and physiological functions with external day/night cycles. Breakdown of circadian rhythms such as sleep/wake cycles is associated with the onset of several neurological diseases; however, it is not clear whether disruption of rhythms is a...
Estradiol (E2) plays a role in positive and negative feedback mechanisms of the hypothalamic-pituitary-gonadal (HPG) axis in female mammals. These mechanisms are regulated by two different populations of kisspeptin (KP)-producing neurons: anteroventral periventricular (AVPV) neurons, which are stimulated by E2, and arcuate (arc) neurons, which are inhibited by E2. AVPV...
Altogether, this dissertation highlights the value of mass spectrometry-based analysis of intact proteins for solving problems related to understanding disease mechanisms and developing new therapeutics.
Mutations to the antioxidant enzyme Cu, Zn Superoxide Dismutase (SOD1) perturb protein structure in vivo to cause 2-5% of amyotrophic lateral sclerosis (ALS) cases. Metal-deficient...
Multicellular coordination in response to environmental stimuli is essential in biology, and this coordination is often achieved by a division of labor to establish leaders and followers in a cell population. This is called emergent leadership, but how a cell adopts its role and effectively exchanges information with peers is...
Cervical cancer is the fourth most common cancer in women worldwide with human papillomavirus (HPV) being the main cause of the disease. Currently available treatment methods are limited and emphasize the need for discovery of new therapies that improve patient outcome. Chromosomal amplifications have been identified as a source of...