BCL11B, also known as CTIP2, is a transcription factor which plays a critical role in the regulation and development of many tissues and organ systems, including the skin. A 2019 study by Goos et. al. uncovered a novel point mutation in BCL11B gene that converted the Arginine(R)-3 residue to a...
______________________________________________________________________________
MarkLeid, Committee Member, representing Washington State University College of Pharmacy
and
The red-sided garter snakes (Thamnophis sirtalis parietalis) of Manitoba, Canada, have been extensively studied for decades with little investigation into their immune system. These animals live very close to the arctic circle and spend over half of the year underground brumating. The annual cycle of the red-sided garter snakes make...
Molecular genetic and enzymological techniques have been employed to study secondary metabolite biosynthesis. These investigations have focused on two projects: the cloning and heterologous expression of biosynthetic gene clusters from unculturable marine organisms and the characterization of individual enzymes involved in the biosynthesis of the antifungal agent blasticidin S. The...
The emerging field of regenerative medicine is mainly approached by two different aspects. First is the use of stem cell based models to generate a suite of differentiated cells for therapeutic applications and the alternative approach is to utilize the non-mammalian models that have the inherent capacity to regenerate their...
The unfolding of human retinoid X receptor α in the presence of the denaturant guanidine HCl was studied using stopped-flow absorbance spectroscopy. The protein's four native cysteine residues were mutated to obtain four single-cysteine mutants, each with the other three cysteine residues mutated to alanine. The thiols of these hRXRα...
Ovarian cancer, “the silent killer,” is one of the deadliest gynecological diseases due to delayed diagnosis, leading to a heavily disseminated and aggressive metastatic cancer. Therapeutic options are limited at stages III-IV of ovarian cancer, in which debulking surgery and cytotoxic chemotherapy remain the mainstays of
intervention. However, these therapeutic...
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...
Cnidarians and their symbiotic dinoflagellates form a productive mutualism that shapes marine environments. In this symbiosis, dinoflagellate species from the family Symbiodiniacea reside within cnidarian host gastrodermal cells and provide the host with photosynthetically fixed carbon in exchange for host metabolites. This nutritional exchange allows both partners to thrive in...
Leukemogenesis, uncontrolled proliferation of dysfunctional, transformed immature lymphocytes, appears, especially in children, to be associated with abrogation of normal lymphopoiesis, and thymopoiesis in the case of T cell leukemias. Sequence specific transcription factors (SSTFs) are nuclear control switches that respond to cellular signals to alter cell state and cell fate...
The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that is a member of the basic helix-loop-helix PER-ARNT-SIM (bHLH/PAS) protein family of cellular sensors. The AHR is conserved across multiple animal phyla and is required for proper vertebrate development. A structurally diverse group of chemicals, including polycyclic aromatic...
Mammalian skin is the largest organ of the body and serves as a barrier to protect the body against chemical, mechanical and pathogenic insults as well as water loss. The epidermis is formed from the primitive ectoderm into a multilayered stratified epithelium, consisting of basal, spinous, granular and outermost cornified...
Melanoma is the deadliest form of skin cancer, arising from malignant transformation of pigment-producing melanocytes. The primary risk factor for melanoma and other skin cancers is DNA damage resulting from unprotected solar ultraviolet radiation (UVR). If incorrectly repaired, this damage can result in incorporation of mutations that cause aberrant cell...
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...
Cutaneous melanoma remains the deadliest form of skin cancer, with a
diagnosis of metastasis indicating a median survival rate of less than a year. Solar ultraviolet (UV) radiation, especially childhood sun exposure, is an important etiological risk factor of melanoma. Previous studies determined that mice selectively lacking the nuclear hormone...
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....
Recombinant human calpain-5 was expressed in insect cells using a baculovirus system. The expressed calpain-5 was purified by both traditional chromatography and by affinity-column chromatography. Both methods yielded active protease. Calpain-5 displayed very limited hydrophobicity. This indicated that calpain-5 is not a membrane binding protein. Calpain-5 had pI of 8.3....
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...
Numerous human conditions would be improved if therapies to encourage tissue regeneration were available. The goal of regenerative medicine is to encourage the body's intrinsic ability to repair and restore tissues lost by disease, injury or aging. While certain vertebrates have the inherent capacity to regenerate, mammals do not. To...
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...
Phospholipase C-β (PLC-β) isozymes are key effectors in G protein-coupled
signaling pathways. Prior research suggested that some isoforms of PLC-β may exist
and function as dimers, but little is known about dimerization of PLC-β. Data from coimmunoprecipitation
assays of differentially-tagged PLC-β constructs and sizeexclusion
chromatography of native PLC-β support homodimerization...
Homeodomain transcription factors control developmental processes. They pattern body formation, specify cell lineages and switch the onset of gene regulatory cascades. Pitx2, a bicoid-related homeodomain transcription factor, is asymmetrically expressed in the left lateral plate mesoderm and mesoderm-derived tissues. Pitx2 null mice are characterized by failure of body wall closure,...
White mold, caused by Sclerotinia sclerotiorum (Lib.) De Bary, is a destructive yield-limiting disease of common bean (Phaseolus vulgaris L.). Genetic resistance to this pathogen is limited in common bean. Identification of high levels of partial physiological resistance in a genetically cross compatible species, Phaseolus coccineus, is advisable. The objectives...
Skeletal muscle, the largest organ in the body in mass, is composed by 600 specialized muscles in humans with unique biochemical, physiological and metabolic identities. Skeletal muscles control body movement, locomotion, and nutrient balance. Muscle formation requires precisely orchestrated environmental signals and regulatory gene networks in time and space. Gene...
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...
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...