Current Research Projects
"Mechanistic Analysis of Nanomaterial Induced Mitophagy.” Nanomaterials are hypothesized to exert their toxicity by the induction of reactive oxygen species (ROS). Increased ROS has a profound effect on the health of mitochondria, as the mitochondrion generates low levels of ROS and relies on a REDOX homeostasis to keep up with the energy demand of the cell. Multiple molecular biology techniques such as Western blotting, PCR, and ELISA were employed to analyze mitochondrial specific mitophagy pathways as well as the electron transport chain. This type of analysis will provide insight into the pathway of ROS induced cellular death.
"Changes in Mitochondrial Health After Nanomaterial Exposure: A Useful Biomarker in Toxicology Research." The structure and function of the mitochondria in mammalian cells is an important indicator of human health. This talk discusses our work that uses the mitochondria as a non-invasive biosensor of exposure after exposure to a variety of engineered nanomaterials. The mitochondria exist in a state of homeostasis with certain processes undergoing constant flux. The constrained, yet fluid, nature of mitochondrial morphology, ATP production, and oxygen consumption allow measurements of mitochondrial processes to give robust results following a low dose exposure to toxicants or environmental contaminants. We used aluminum nanoparticles as a challenge for this model. At high exposure concentrations (i.e. 1 mg/kg/day), aluminum in its ionic form functions as a deregulator of normal mitochondrial activity. The health effects of aluminum particle exposure are unknown. We found a dose-response change in coupling efficiency between ATP production and oxidative phosphorylation in this system. This result corresponds to the increase in reactive species (oxygen and nitrogen) detected in cells as well as a decrease in cellular viability. The consequence of this decoupling, increased oxidative stress, and decrease in viability relate to alterations in the response to energy demand. The resultant adverse effect could be labeled as an initiator for the onset of mitochondrial and metabolic diseases. More research that examines the health of the mitochondria is needed, but has the potential to aid in determining mechanisms of toxic action related to low dose exposures of many different environmental contaminants.
Collaborator(s): Air Force Research Labs
“Determining the biological mechanisms of action for environmental exposures: Applying CRISPR/Cas9 to toxicological assessments”. As the rapidly evolving field of nanotechnology continues to increase the number of products containing advanced materials, it is imperative that the field of toxicology maintains the same growth and adapt to properly guide public health safety recommendations. To date, the mechanisms of toxic action for most metal-based engineered nanomaterials are hypothesized as oxidative stress through the generation of reactive oxygen species (ROS). However, the exact mechanism of action or pathway through which toxicity is induced remains unknown. However, these mechanisms of toxicity can be uncovered by reviewing the techniques and validation studies undertaken by toxicologist in other fields. Specifically, the emergence of new laboratory techniques such as the CRISPR/Cas9 system for single gene knock-outs, CRISPR interference (CRISPRi), and CRISPR libraries, it is now possible to elucidate the exact mechanism through which metallic nanomaterials perturb normal cellular function.
Collaborator(s): Air Force Research Labs
"Comprehensive Physicochemical Characterization of Nanocellulose Materials”. The major goal of this work is to detect and measure the nanometer-sized components within micro-fibrillated cellulose materials. Physicochemical characterization of the materials include microscopy, spectroscopy, spectrometry, and chromatography.
Investigator(s): Marina Mulenos George, Thelma Ameh, Desirae Carrassco
"Synthesis and characterization of nanometer sized liposomes for encapsulation and microRNA transfer to breast cancer cells”. The use of liposomes as a drug delivery carrier (DDC) for the treatment of various diseases, especially cancer, is rapidly increasing, requiring more stringent synthesis, formulation, and preservation techniques to bolster safety and efficacy. Liposomes, otherwise referred to as phospholipoid vesicles are self-assembled colloidal particles. When formed in either the micrometer or nanometer size range they are ideal candidates as DDC because of their biological availability, performance, activity, and compatibility. Defining and addressing the critical quality attributes (CQA) along the pharmaceutical production scale will enable a higher level of quality control for reproducibility. Data shows that microRNA can be loaded into nanometer-sized liposomes, preserved for months in a dried form, and maintain encapsulation after extended time periods in storage.
"Comparing the Basal-level Gene and Protein Expressions of Human Cell-Types”. Using cell culture-based models to measure the hazards of particle systems has become routine and derivative over the past few years. The research presented in this study analyzes the differences among cells retrieved from varying depths of the pulmonary system and in varying diseased states. There is a need to advance cell line use and suggest guidelines on which cells to use for specific experiments.
"Comprehensive Physicochemical Characterization of Nickel Colloid and Nickel Oxide Nanomaterials: Challenges and Opportunities for Environmental Health”. The objective of this study is to execute a comprehensive material characterization of four nickel nanomaterials, investigating the chemical nature (i.e. chemical composition, surface reactivity, and ion-to-particle ratios in aqueous suspensions) and physical properties (i.e. size and size distribution, morphology, and aggregation/agglomeration state).
Investigator(s): Marina Mulenos George, Desirae Carrassco, Daniel Kang
“Characterizing Nanoparticle–Protein Coronas: Using Analytical Methods to Detect and Identify Proteins Adsorbed onto Gold Particle Surfaces”. The use of nanomaterials in pharmaceutical research is increasing. Engineered nanomaterials have been proposed as drug-carriers and can deliver precise doses of specific drugs to targeted locations. However, upon entering blood stream, proteins readily adsorb onto and desorb from the surface of these drug products. This cloud of adsorbed proteins is known as the ‘protein corona’ and is postulated to critically alter either the drug product’s therapeutic (positive) or toxicological (negative) effects. In order to understand the effects related to the protein corona, detection and identification of the proteins which make up the corona is necessary. Data suggest that control over protein corona formation is dependent on particle surface chemistry may be predictable, and holds promise as an engineering technique to employ therapies.
Investigator(s): London Steele, Marina Mulenos George, Andreanna Burman
“Antimicrobial Encapsulated Nanoparticles Project”. Vector control has become a public health crisis for humans, animal wildlife, and plant health. While most vector eradication methods have focused on pathogens spread in human populations, pathogens that spread in plant populations are equally detrimental. Plant health is a central tenant in the agriculture industry. When a segment of agriculture is damaged by a disease or pathogen spread by an organism, the industry risks substantial economic and sustainability losses. The goal of this proposal is to develop a series of proto-typical Antimicrobial Encapsulated Nanoparticle Systems that demonstrate multi-functional properties in the delivery of antibacterial, pesticidal, and/or therapeutic activity to Asian citrus psyllid, CandidatusLiberibacterbacteria, and/or citrus trees, respectively.
Investigator(s): Thelma Ameh, Bailey Sharp