Stanley M. Stevens, Jr.

Stanley M. Stevens, Jr.
University of South Florida | USF · Department of Cell Biology, Microbiology and Molecular Biology

Ph.D.

About

133
Publications
19,180
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Introduction
Mass spectrometry (MS)-based proteomics is a powerful, unbiased approach to understand the complex molecular mechanisms underlying fundamental biological processes as well as mechanisms associated with the development and progression of human disease. This approach is an integral component of our research program, where we are currently investigating epigenetics changes that occur in various cell and tissue types after chronic alcohol use. Specifically, we utilize MS to identify and quantify changes in alcohol-induced histone modifications as well as differential protein expression on a global scale in cell culture and animal models of acute and chronic alcohol exposure.
Additional affiliations
January 2009 - August 2015
University of South Florida
Position
  • Professor (Assistant)

Publications

Publications (133)
Article
Trapped ion-mobility spectrometry (TIMS) was used to fractionate ions in the gas phase based on their ion mobility (V s/cm2), followed by parallel accumulation-serial fragmentation (PASEF) using a quadrupole time-of-flight instrument to determine the effect on the depth of proteome coverage. TIMS fractionation (up to four gas-phase fractions) coupl...
Article
Full-text available
Alcohol overconsumption is a major cause of preventable mental disorders and death in the United States and around the world. The pathogenesis of alcohol dependence, abuse, and toxicity to the central nervous system remains incompletely understood. Cell culture-based models have been highly valuable in studying the molecular and cellular mechanisms...
Article
As the resident immune cells in the central nervous system, microglia play an important role in the maintenance of its homeostasis. Dysregulation of microglia has been associated with the development and maintenance of chronic pain. However, the relevant molecular pathways remain poorly defined. In this study, we used a mass spectrometry-based prot...
Article
Full-text available
The microtubule-associated protein tau pathologically accumulates and aggregates in Alzheimer’s disease (AD) and other tauopathies, leading to cognitive dysfunction and neuronal loss. Molecular chaperones, like small heat-shock proteins (sHsps), can help deter the accumulation of misfolded proteins, such as tau. Here, we tested the hypothesis that...
Article
Full-text available
Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphe...
Article
Background: Acute intoxication caused by binge ethanol drinking is linked to widespread impairments in brain functions. Various alcohol administration paradigms have been used in animals to model the heterogenous clinical manifestation of intoxication in people. It is challenging to model a procedure that produces "visible intoxication" in rodents...
Article
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Malignant transformation of fallopian tube secretory epithelial cells (FTSECs) is a key contributing event to the development of high-grade serous ovarian carcinoma (HGSOC). Our recent findings implicate oncogenic transformative events in chronic iron-exposed FTSECs, including increased expression of oncogenic mediators, increased telomerase transc...
Article
Oxidative and nitrative stress have been implicated in the molecular mechanisms underlying a variety of biological processes and disease states including cancer, aging, cardiovascular disease, neurological disorders, diabetes, and alcohol‐induced liver injury. One marker of nitrative stress is the formation of 3‐nitrotyrosine, or protein tyrosine n...
Article
Background Microglia are the resident immune cells in the brain where they play essential roles in the development and maintenance of physiological functions of this organ. Aberrant activation of microglia is speculated to be involved in the pathogenesis of a variety of neurological disorders, including alcohol use disorders. Repeated binge ethanol...
Article
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Type 1 diabetes (T1D) results in the loss of pancreatic beta cells and subsequent loss of insulin production. Exogenous insulin is the only effective treatment, but there is still no cure or interventional therapy available to inhibit progression of T1D. Successful T1D interventional therapy must protect pancreatic beta cells from autoimmunity whil...
Article
Microglia, the resident immune cells of the brain, can exhibit a broad range of activation phenotypes, many of which have been implicated in several diseases and disorders of the central nervous system including those related to alcohol abuse. Given the complexity of global-scale molecular changes that define microglial activation, accurate phenoty...
Article
Full-text available
Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide clinical benefits over chemotherapy for lung cancer patients with EGFR activating mutations. Despite initial clinical responses, long‐term efficacy is not possible because of acquired resistance to these therapies. We have developed EGFR TKI drug‐tolerant (DT...
Article
Microglia, as the resident brain immune cells, can exhibit a broad range of activation phenotypes, which have been implicated in a multitude of central nervous system disorders. Current widely studied microglial cell lines are mainly derived from neonatal rodent brain which can limit their relevance to homeostatic function and disease‐related neuro...
Article
Although iron is essential for cell survival, dysregulated levels can contribute to cancer development or even cell death. The underlying mechanisms mediating these events remain unclear. Herein, we assessed proteomic alterations in iron‐treated ovarian cell lines using Reverse Phase Protein Array (RPPA) technology and potential functional response...
Article
Full-text available
Background Epigenetic dysregulation through ethanol‐induced changes in DNA methylation and histone modifications has been implicated in several alcohol‐related disorders such as alcoholic liver disease (ALD). Ethanol metabolism in the liver results in the formation of acetate, a metabolite that can be converted to acetyl‐CoA, which can then be used...
Conference Paper
Objectives: Lung cancer is the number one cause of cancer-related deaths. About 20% of all non-small cell lung cancer (NSCLC) patients are expected to harbor an Epidermal Growth Factor Receptor (EGFR) activating mutation. First- and second-generation EGFR tyrosine kinase inhibitors (TKIs) are clinically approved to treat advanced NSCLC patients. Ho...
Article
Full-text available
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein accumulation and loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Increased levels of alpha-synuclein have been shown to result in loss of mitochondrial electron transport chain complex I activity leading to increased reactive oxy...
Article
Neuroinflammation, especially activation of microglia, the key immune cells in the brain, has been proposed to contribute to the pathogenesis of ischemic stroke. However, the dynamics and the potential mediators of microglial activation following ischemic neuronal injury are not well understood. In this study, using oxygen/glucose deprivation and r...
Chapter
Stable isotope labeling by amino acids in cell culture (SILAC) is a versatile mass spectrometry-based proteomic approach that can achieve accurate relative protein quantitation on a global scale. In this approach, proteins are labeled while being synthesized by the cell due to the presence of certain amino acids exclusively as heavier mass analogs...
Chapter
Microglia have increasingly been recognized as playing a wide spectrum of roles in various physiological and pathological processes in the central nervous system. Studies in the past have mostly associated individual microglial enzymes or soluble factors such as cytokines with specific functions of microglia. Stable isotope labeling with amino acid...
Article
Full-text available
Background Age is the primary risk factor for many diseases. As such, age is a critical co-factor for examination in order to understand the progression and potential intervention in disease progression. Studies examining both the phenotype and transcriptome of aged microglia demonstrated a propensity for the development of a pro-inflammatory pheno...
Book
Full-text available
This new second edition provides updated and novel protocols of neuroproteomics methods that encompass both global-scale as well as targeted and specialized topics, which are timely additions for the molecular and phenotypic analysis of the central nervous system and CNS-related disorders. The detailed contents of this book include the exploration...
Article
Full-text available
Importance: DIC uptake and fixation by autotrophs is the primary input of inorganic carbon into the biosphere. The mechanism for dissolved inorganic carbon uptake has only been characterized for cyanobacteria despite the importance of DIC uptake by autotrophic microorganisms from many phyla among the Bacteria and Archaea. In this work, proteins ne...
Chapter
Exosomes and microvesicles are extracellular vesicles (EVs) released by most cell types. The role of EVs as a method of intercellular communication has led to these vesicles becoming a major area of interest in a variety of scientific fields including neuroscience. Emerging evidence is now demonstrating that the biomolecular composition of EVs, esp...
Book
This new edition provides updated and novel protocols of neuroproteomics methods that encompass both global-scale as well as targeted and specialized topics, which are timely additions for the molecular and phenotypic analysis of the central nervous system and CNS-related disorders. The detailed contents of this book include the exploration of seve...
Article
Full-text available
BMI1 is a component of the Polycomb Repressive Complex 1 (PRC1), which plays a key role in maintaining epigenetic silencing during development. BMI1 also participates in gene silencing during DNA damage response, but the precise downstream function of BMI1 in gene silencing is unclear. Here we identified the UBR5 E3 ligase as a downstream factor of...
Article
Full-text available
This article contains raw and processed data related to research published in “Quantitative Proteomic Profiling Reveals Hepatic Lipogenesis and Liver X Receptor Activation in the PANDER Transgenic Model” [1], and was generated by “spike-in” SILAC-based proteomic analysis of livers obtained from the PANcreatic-Derived factor (PANDER) transgenic mous...
Article
PANcreatic-DERived factor (PANDER) is a member of a superfamily of FAM3 proteins modulating glycemic levels by metabolic regulation of the liver and pancreas. The precise PANDER-induced hepatic signaling mechanism is still being elucidated and has been very complex due to the pleiotropic nature of this novel hormone. Our PANDER transgenic (PANTG) m...
Poster
Full-text available
In this study, we used both cell culture and animal models to investigate the significance of PHPT1 and pHis signaling in ethanol-induced liver injury. Hepatic ethanol response upon modulation of PHPT1 expression was investigated using advanced mass spectrometry-based phenotypic characterization. Using this approach, we identified altered PHPT1 exp...
Article
It is now known that proteins associated with neurodegenerative disease can spread throughout the brain in a prionlike manner. However, the mechanisms regulating the trans-synaptic spread propagation, including the neuronal release of these proteins, remain unknown. The interaction of neurodegenerative disease-associated proteins with the molecular...
Article
Full-text available
Activation of the sensory nerve ion channel TRPA1 by electrophiles is the key mechanism that initiates nociceptive signaling, and leads to defensive reflexes and avoidance behaviors, during oxidative stress in mammals. TRPA1 is rapidly activated by subtoxic levels of electrophiles, but it is unclear how TRPA1 outcompetes cellular antioxidants that...
Article
Full-text available
Phosphohistidine phosphatase 1 (PHPT1), the only known phosphohistidine phosphatase in mammals, regulates phosphohistidine levels of several proteins including those involved in signaling, lipid metabolism, and potassium ion transport. While the high-resolution structure of human PHPT1 (hPHPT1) is available and residues important for substrate bind...
Article
Full-text available
Alzheimer's disease (AD) is the most common form of dementia and the 6th leading cause of death in the United States. The major pathological hallmarks observed in AD include the formation of intracellular neurofibrillary tangles comprised of phosphorylated forms of the microtubule associated protein tau, and the deposition of extracellular plaques...
Article
Microglia play important and dynamic roles in mediating a variety of physiological and pathological processes during the development, normal function and degeneration of the central nervous system. Application of SILAC-based proteomic analysis would greatly facilitate the identification of cellular pathways regulating the multifaceted phenotypes of...
Article
Full-text available
Amyloid Precursor Protein (APP) is regulated in a mitosis-specific manner and plays a role in proliferative signaling in cells. Though APP-derived Aβ generation has a well-established role in neurodegeneration, the mechanistic role of APP in this process is not fully understood. Here, we performed an unbiased, comprehensive analysis of the phosphop...
Article
Full-text available
Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (M...
Article
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The rodent malaria parasite Plasmodium berghei is a practical model organism for experimental studies of human malaria. Plasmepsins are a class of aspartic proteinase isoforms that exert multiple pathological effects in malaria parasites. Plasmepsins residing in the food vacuole (FV) of the parasite hydrolyze hemoglobin in red blood cells. In this...
Article
Full-text available
Microglia, the resident immune cells of the brain, have been shown to display a complex spectrum of roles that span from neurotrophic to neurotoxic depending on their activation status. Microglia can be classified into four stages of activation, M1, which most closely matches the classical (pro-inflammatory) activation stage, and the alternative ac...
Article
Full-text available
Identification of protein residues from prehistoric cooking pottery using mass spectrometry is challenging because proteins are removed from original tissues, are degraded from cooking, may be poorly preserved due to diagenesis, and occur in a palimpsest of exogenous soil proteins. In contrast, bone proteins are abundant and well preserved. This re...
Article
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The constitutively expressed heat shock protein 70 kDa (Hsc70) is a major chaperone protein responsible for maintaining proteostasis, yet how its structure translates into functional decisions regarding client fate is still unclear. We previously showed that Hsc70 preserved aberrant tau, but it remained unknown if selective inhibition of the activi...
Article
Full-text available
Staphylococcus aureus possesses a lone extracytoplasmic function (ECF) sigma factor, σS. In Bacillus subtilis, the ECF sigma factor, σW, is activated through a proteolytic cascade that begins with cleavage of the RsiW anti-sigma factor by a site-1 protease (S1P), PrsW. We have identified a PrsW homolog in S. aureus (termed PrsS) and explored its ro...
Article
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Proteomics is a powerful approach used for investigating the complex molecular mechanisms of disease pathogenesis and progression. An important challenge in modern protein profiling approaches involves targeting of specific protein activities in order to identify altered molecular processes associated with disease pathophysiology. Adenosine-binding...
Article
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The overproduction of reactive oxygen and nitrogen species (ROS and RNS) can have deleterious effects in the cell, including structural and possible activity-altering modifications to proteins. Peroxynitrite is one such RNS that can result in a specific protein modification, nitration of tyrosine residues to form nitrotyrosine, and to date, the ide...
Article
Full-text available
PANcreatic-DERived factor (PANDER, FAM3B) is a novel protein that is highly expressed within the endocrine pancreas and to a lesser degree in other tissues. Under glucose stimulation, PANDER is co-secreted with insulin from the β-cell. Despite prior creation and characterization of acute hepatic PANDER animal models, the physiologic function remain...