Natural products from both terrestrial and marine sources represent a significant source of novel drug leads, and have previously been developed into clinically-approved agents for the treatment of various human diseases. This work represents the biological characterization of the mechanistic basis for activity of several natural product structures in models...
The integumentary system is the largest organ system of the body that comprises of skin and its appendages such as hair follicles, sebaceous and sweat glands. Skin is divided into three distinct structural layers: the epidermis, dermis and hypodermis. The epidermis originates from the ectoderm and is composed of four...
Human cathelicidin antimicrobial peptide (CAMP/LL-37) is a cationic antimicrobial peptide that is widely expressed by myeloid and epithelial cells at the human-environment interface. It possesses broad spectrum antimicrobial capacity against bacteria, fungi and viruses. In addition to its direct antimicrobial activity, CAMP/LL-37 also attracts and recruits monocytes, neutrophils and other...
The aryl hydrocarbon receptor (AhR) has recently been described as a novel therapeutic target, given the potent suppression of multiple immune-mediated diseases following activation by the prototypic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In the parent-into-F1 graft-versus-host (GVH) model, suppression of the cytotoxic T-lymphocyte (CTL) response is associated with the presence of CD25⁺CTLA-4⁺IL-10⁺Foxp3[superscript...
Billions of pounds of bisphenol A (BPA) are produced annually around the globe for the manufacture of numerous consumer products, including polycarbonate food and water containers, the protective resin linings of food cans, thermal printing paper, and dental fillings. BPA exposure during nervous system development has been associated with learning...
Skin is the largest organ in the body that protects the organism from environmental, chemical and physical traumas of each passing day. The protective skin epidermal permeability barrier (EPB) is formed within the exterior layers of the epidermis, which are regularly sloughed off and repopulated by movement of inner cells....
Targeting the epigenome, including the use of histone deacetylase (HDAC) inhibitors, is a novel strategy for cancer chemoprevention. Sulforaphane (SFN), a compound found at high levels in broccoli and broccoli sprouts, is a potent inducer of Phase 2 detoxification enzymes and inhibits tumorigenesis in animal models. SFN also has a...
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds are well-recognized for their immunosuppressive activity, which is mediated through an intracellular receptor and transcription factor, aryl hydrocarbon receptor (AhR). Laboratory animals exposed to TCDD are less resistant to infection and have severely impaired humoral and cell-mediated immune responses. This dissertation addressed the hypothesis that...
The immune toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been studied for over 35 years, but only recently has the profound immune suppression associated with TCDD exposure been linked to induction of regulatory T cells (Tregs). The effects of TCDD are mediated through binding the aryl hydrocarbon receptor (AhR), a ligand-activated transcription...
EF-hand proteins are a conserved family of proteins that are modulated by divalent cations and regulate diverse cellular activities. In the present study we characterized the molecular determinants of myosin regulatory light chain (RLC) interaction with several subunits of the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Myosin RLC is an EF-hand protein...