Anthony J. Saviola
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View article: Targeting nicotinamide salvage pathway is a unique metabolic vulnerability of high-risk MDS stem cells
Targeting nicotinamide salvage pathway is a unique metabolic vulnerability of high-risk MDS stem cells Open
Background: High-risk myelodysplastic syndrome (MDS) is an incurable age-related clonal disorder of the hematopoietic stem cell (HSPC). The current standard of care for MDS patients is hypomethylating agents, like azacitidine; however, onl…
View article: Cardiomyocyte-expressed TGFβ signals to fibroblasts to program early heart maturation and adult myocyte identity
Cardiomyocyte-expressed TGFβ signals to fibroblasts to program early heart maturation and adult myocyte identity Open
Transforming growth factor β (TGFβ) is a secreted growth factor that is sequestered to the extracellular matrix (ECM) as a latent complex. In adult disease TGFβ release in the heart transforms fibroblasts into a differentiated state that s…
View article: Development of a Vaginal Extracellular Matrix Hydrogel for Combating Genitourinary Syndrome of Menopause
Development of a Vaginal Extracellular Matrix Hydrogel for Combating Genitourinary Syndrome of Menopause Open
Genitourinary syndrome of menopause (GSM) is initiated by the hypoestrogenic state consequent to cessation of ovarian function and involves changes in all vaginal layers. These alterations include decreased epithelial proliferation and dif…
View article: Proteomic characterization of type I collagen N-terminal crosslinked peptides
Proteomic characterization of type I collagen N-terminal crosslinked peptides Open
Collagen cross-links mediated by the lysyl oxidase and lysyl hydroxylase families of enzymes significantly contribute to the biomechanical strength and rigidity of tissues, influencing cell signaling and the downstream cell phenotype. In t…
View article: Structural and functional characterisation of isolated puff adder (<i>B. arietans</i>) serine proteases
Structural and functional characterisation of isolated puff adder (<i>B. arietans</i>) serine proteases Open
Serine proteases are known to play a major role in the haemotoxic actions of viper venom, but compared with those from other vipers, the serine proteases of puff adder venoms have not been extensively characterised. To address this, we iso…
View article: Volumetric printed biomimetic scaffolds support in vitro lactation of human milk-derived mammary epithelial cells
Volumetric printed biomimetic scaffolds support in vitro lactation of human milk-derived mammary epithelial cells Open
The human breast is remarkably plastic and remodels with each birth to produce milk optimally suited for the changing demands of the newborn. This dynamic nature of lactation makes it challenging to study under controlled conditions. Given…
View article: Human Retinal Organoid Model of Disease-Relevant Photoreceptor Cell Death Amenable to Drug Screening
Human Retinal Organoid Model of Disease-Relevant Photoreceptor Cell Death Amenable to Drug Screening Open
Dry age-related macular degeneration (AMD) is characterized by the progressive loss of retinal pigment epithelium cells in the macula, leading to photoreceptor degeneration and loss of central vision. Current treatments only modestly delay…
View article: Delayed blastocyst development is associated with altered metabolism and proteome in male and female bovine embryos
Delayed blastocyst development is associated with altered metabolism and proteome in male and female bovine embryos Open
Developmentally delayed embryos are associated with reduced implantation potential and live birth rates; however, inherent causes of delayed development are not well understood. Metabolism during preimplantation development is responsible …
View article: Volumetric printed biomimetic scaffolds support <i>in vitro</i> lactation of human milk-derived mammary epithelial cells
Volumetric printed biomimetic scaffolds support <i>in vitro</i> lactation of human milk-derived mammary epithelial cells Open
The human breast is remarkably plastic and remodels with each birth to produce milk optimally suited for the changing demands of the newborn. This dynamic nature of lactation makes it challenging to study under controlled conditions. Given…
View article: Divergent response to radio-immunotherapy is defined by intrinsic features of the tumor microenvironment
Divergent response to radio-immunotherapy is defined by intrinsic features of the tumor microenvironment Open
Background Treatment with immunotherapy can elicit varying responses across cancer types, and the mechanistic underpinnings that contribute to response vrsus progression remain poorly understood. However, to date there are few preclinical …
View article: <i>Streptococcus pneumoniae</i><scp>GAPN</scp> is a key metabolic player necessary for host infection
<i>Streptococcus pneumoniae</i><span>GAPN</span> is a key metabolic player necessary for host infection Open
Streptococcus pneumoniae ( S. pneumoniae ) employs various metabolic pathways to generate nicotinamide adenine dinucleotide phosphate (NADPH), which is essential for redox balance, fatty acid synthesis, and energy production. GAPN, a non‐p…
View article: Biophysical characterization of the dystrophin C-terminal domain: Dystrophin interacts differentially with dystrobrevin isoforms
Biophysical characterization of the dystrophin C-terminal domain: Dystrophin interacts differentially with dystrobrevin isoforms Open
Duchenne muscular dystrophy (DMD) gene encodes dystrophin, a large multidomain protein. Its nonfunctionality leads to dystrophinopathies like DMD and Becker muscular dystrophy, for which no cure is yet available. A few therapies targeted t…
View article: A bovine model of hypoxia-induced pulmonary hypertension reveals a gradient of immune and matrisome response with a complement signature found in circulation
A bovine model of hypoxia-induced pulmonary hypertension reveals a gradient of immune and matrisome response with a complement signature found in circulation Open
Extensive immune cell infiltration and matrisome alterations associated with hypoxia-induced pulmonary hypertension in a large mammal model. Matrisome components correlate with increased resistance to identify candidate alterations that dr…
View article: Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC
Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC Open
The EphB4-ephrinB2 signaling axis has been heavily implicated in metastasis across numerous cancer types. Our emerging understanding of the dichotomous roles that EphB4 and ephrinB2 play in head and neck squamous cell carcinoma (HNSCC) pos…
View article: IL15/IL15Rα complex induces an anti-tumor immune response following radiation therapy only in the absence of Tregs and fails to induce expansion of progenitor TCF1+ CD8 T cells
IL15/IL15Rα complex induces an anti-tumor immune response following radiation therapy only in the absence of Tregs and fails to induce expansion of progenitor TCF1+ CD8 T cells Open
Background This work seeks to understand whether IL15-incorporating treatments improve response to radiotherapy and uncover mechanistic rationale for overcoming resistance to IL15 agonism using novel therapeutic combinations. Experimental …
View article: Discerning Specific Thrombolytic Activities and Blood Clot Degradomes of Diverse Snake Venoms with Untargeted Peptidomics
Discerning Specific Thrombolytic Activities and Blood Clot Degradomes of Diverse Snake Venoms with Untargeted Peptidomics Open
Identification and characterization of snake venom toxins that interfere with hemostasis have important implications for the treatment of snake envenomation, the bioprospecting of therapeutically useful molecules, and the development of re…
View article: The pro-tumoral and anti-tumoral roles of EphA4 on T regulatory cells and tumor associated macrophages during HNSCC tumor progression
The pro-tumoral and anti-tumoral roles of EphA4 on T regulatory cells and tumor associated macrophages during HNSCC tumor progression Open
Head and Neck Squamous Cell Carcinoma (HNSCC) is a deadly cancer with poor response to targeted therapy, largely driven by an immunosuppressive tumor microenvironment (TME). Here we examine the immune-modulatory role of the receptor tyrosi…
View article: Suppression of the host antiviral response by non-infectious varicella zoster virus extracellular vesicles
Suppression of the host antiviral response by non-infectious varicella zoster virus extracellular vesicles Open
Varicella zoster virus (VZV) reactivates from ganglionic sensory neurons to produce herpes zoster (shingles) in a unilateral dermatomal distribution, typically in the thoracic region. Reactivation not only heightens the risk of stroke and …
View article: Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC
Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC Open
The EphB4-ephrinB2 signaling axis has been heavily implicated in metastasis across numerous cancer types. Our emerging understanding of the dichotomous roles that EphB4 and ephrinB2 play in head and neck squamous cell carcinoma (HNSCC) pos…
View article: Complex compositional and functional diversity of venom metalloproteinases in African puff adders
Complex compositional and functional diversity of venom metalloproteinases in African puff adders Open
The puff adder ( Bitis arietans ) is a highly venomous viper responsible for many fatalities in Africa, yet there have been few comprehensive analyses of its venom proteins, particularly of the proteases that play a key role in pathology o…
View article: Diverse Gene Regulatory Mechanisms Alter Rattlesnake Venom Gene Expression at Fine Evolutionary Scales
Diverse Gene Regulatory Mechanisms Alter Rattlesnake Venom Gene Expression at Fine Evolutionary Scales Open
Understanding and predicting the relationships between genotype and phenotype is often challenging, largely due to the complex nature of eukaryotic gene regulation. A step towards this goal is to map how phenotypic diversity evolves throug…
View article: Figure S1-S7 from PPARα Agonism Enhances Immune Response to Radiotherapy While Dietary Oleic Acid Results in Counteraction
Figure S1-S7 from PPARα Agonism Enhances Immune Response to Radiotherapy While Dietary Oleic Acid Results in Counteraction Open
Supplemental figures
View article: Figure S1-S7 from PPARα Agonism Enhances Immune Response to Radiotherapy While Dietary Oleic Acid Results in Counteraction
Figure S1-S7 from PPARα Agonism Enhances Immune Response to Radiotherapy While Dietary Oleic Acid Results in Counteraction Open
Supplemental figures
View article: Data from PPARα Agonism Enhances Immune Response to Radiotherapy While Dietary Oleic Acid Results in Counteraction
Data from PPARα Agonism Enhances Immune Response to Radiotherapy While Dietary Oleic Acid Results in Counteraction Open
Purpose:Head and neck cancer (HNC) improvements are stagnant, even with advances in immunotherapy. Our previous clinical trial data show that altered fatty acid (FA) metabolism correlates with outcome. We hypothesized that pharmacologic an…
View article: Data from PPARα Agonism Enhances Immune Response to Radiotherapy While Dietary Oleic Acid Results in Counteraction
Data from PPARα Agonism Enhances Immune Response to Radiotherapy While Dietary Oleic Acid Results in Counteraction Open
Purpose:Head and neck cancer (HNC) improvements are stagnant, even with advances in immunotherapy. Our previous clinical trial data show that altered fatty acid (FA) metabolism correlates with outcome. We hypothesized that pharmacologic an…
View article: Selected humanization of yeast U1 snRNP leads to global suppression of pre-mRNA splicing and mitochondrial dysfunction in the budding yeast
Selected humanization of yeast U1 snRNP leads to global suppression of pre-mRNA splicing and mitochondrial dysfunction in the budding yeast Open
The recognition of the 5′ splice site (5′ ss) is one of the earliest steps of pre-mRNA splicing. To better understand, the mechanism and regulation of 5′ ss recognition, we selectively humanized components of the yeast U1 (yU1) snRNP to re…