Summer Research

The following students conducted research for RIMI during the summer of 2014:

Student Research
Ryan Dougherty Synthesis and Characterization of Bidentate NiN2S2 Model Complexes
Korey Reid  Insight into Intrinsically Disordered Proteins by F > A Substitution in the FG-Motifs of a Model Nucleoporin
Karina Hernandez and Yesenia Thompson Polymorphism analyses in specific xenobiotic-metabolizing genes of Hispanic farmworkers from the San Joaquin Valley with hormone-dependent cancer
Malika Sahni Metabolomic analysis of HER2-positive breast cancer cells
Austen Scruggs The Investigation of Chemical Aerosols Attributed to the Cigarette Smoke Aging Process and Their Impact in Cellular Toxicological Studies

 

Synthesis and Characterization of Bidentate NiN2S2 Model Complexes

            Some metalloproteins hold possible applications in the area of drug targets, clean energy sources due to their ability to produce hydrogen gas, and using them as models for enantioselective catalysts.  However, more research and investigation is still needed in order to elucidate information about the active sites of these huge proteins.  Model complexes have been shown to be useful for exposing such information.  Most research on model complexes has only pertained to tetradentate ligand systems due to the ease at which they are prepared.  In the Golden Lab, However, we have employed the use of only bidentate ligand systems due to the fact that these ligand systems more closely resemble biological conditions.  Currently in the Golden Lab we are synthesizing and characterizing bidentate nickel complexes that contain a N2S2 coordination sphere, which is a common active site motif found in metalloenzymes.   

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Polymorphism analyses in specific xenobiotic-metabolizing genes of Hispanic farmworkers from the San Joaquin Valley with hormone-dependent cancer

Organochlorines (OC) are a common class of pesticides known as endocrine disruptors in humans.  OC pesticides are known to modify the effects of estrogen and testosterone and may act as agonists or antagonists or have mixed effects in the microenvironment of tissues. The pathway to pesticide (xenobiotic) elimination from the body is a multi-step process resulting in excretion of contaminants through the urine or bile. The first step involves oxidation which is primarily carried out by the Phase I enzyme family, cytochrome P450 (CYP), and is typically an activating reaction creating a more polar byproduct. The second step involves conjugation with an endogenous ligand through a Phase II enzyme family, glutathione-S-transferase (GST), and is typically a detoxifying reaction. The goals of this study have been to determine the association between exposure to OC pesticides and risk of a hormone-dependent cancer (breast or prostate) in the Hispanic population of the intensely agricultural San Joaquin Valley of California. Our case-control study involves the use of DNA samples consented from 42 Hispanic female participants and 180 Hispanic male participants and assesses single nucleotide polymorphisms (SNPs) in select xenobiotic-metabolizing genes utilizing three different molecular strategies. For female samples, we found no association between the GSTM1 null polymorphism and breast cancer risk in this sample (O.R. = 0.99, 95% CI=0.28, 3.51), but did find a doubling in breast cancer risk among those women who carried the null polymorphism for GSTT1 (O.R. = 2.21, 95% CI=0.39, 12.63). In females, two CYP1B1 polymorphisms (codon 119 Ala/Ser and codon 432 Val/Leu) were also genotyped. While no association in breast cancer risk for codon 119 (O.R. = 0.77, 95% CI=0.14, 3.70) was found, we did find elevated risk of breast cancer (O.R. 2.33, 95% CI= 0.64, 8.54) at codon 432 (Val>Leu) suggesting that women carrying the Val CYP1B1 allele had higher risk than those women with the Leu/Leu genotype.  Due to the small sample population, Odds Ratios are deemed statistically unstable and thus one must be prudent in drawing firm conclusions. Analyses of male samples are ongoing. This study indicates that it is feasible to identify, trace, consent and recruit female and male Hispanic participants in the San Joaquin Valley of California who have recently been diagnosed with breast cancer or prostate cancer for future interventional studies.

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The Investigation of Chemical Aerosols Attributed to the Cigarette Smoke Aging Process and Their Impact in Cellular Toxicological Studies

Dr. Alam Hasson, Dr. Viswanathan Krishnan, Dr. Jason Bush, Austen K. Scruggs*,  Annabelle Lolinco, Divine Yang, and Teagan Zoldoske

            Various studies have shown cigarette smoke to be a health hazard to the individual smoker, a health hazard to those exposed, and environmental pollutant. Further studies in the toxicological, biochemical, and biological fields have been conducted that highlight several chemical species as organic, inorganic, physical, and or cellular toxins. Though various studies have investigated several aspects of primary and secondary cigarette smoke, relatively few studies have investigated the chemical fate of cigarette smoke in the atmosphere in conjunction with the impact of aged cigarette smoke in cellular toxicological studies.  The current smoking study here at California State University, Fresno attempts to resolve this issue by conducting a comprehensive research project at the Fresno State through RIMI. RIMI is a conglomerate of many experienced professors, graduate, and undergraduate researchers from various disciplines. The chemical analysis portion of this study is overseen by both Dr. Alam Hasson and Dr. Viswanathan Krishnan. Dr. Alam Hasson investigates the fate of cigarette smoke in the atmosphere utilizing aspects of photochemistry, aerosol chemistry, and gas phase radical chemistry. He utilizes a TE-2 Smoking System, a  Nephelometer, and a Proton Transfer Reaction Mass Spectrometer to evaluate chemical changes both the gas phase and in aerosols exposed to gas phase radicals confined in a Teflon bag chamber in real time. He also utilizes filter extraction techniques to further evaluate aerosols via Gas Chromatography Mass Spectrometry. Dr. Viswanathan Krishnan analyzes aerosol composition and aerosol chemical changes utilizing Nuclear Magnetic Resonance, he performs a battery of complex  experiments on filter extracts provided by Dr. Alam Hasson. The biological and toxicological portion of this study is overseen by Dr. Jason Bush. He utilizes Flow Cytometry and a myriad of other analytical biological techniques to investigate the cellular  toxicity of the various filter extracts produced by Dr. Alam Hasson. The data procured through the coordination of the RIMI personnel are helping to produce more information about the fate of cigarette smoke in the atmosphere and its cellular toxicity. Thus, RIMI and all of its associates are helping to produce a more complete picture of the various impacts cigarettes have on both human health and the environment.

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