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Dr. Jennifer Chase

Northwest Nazarene University

Chemistry Department

jrchase@nnu.edu

Research:

Two of the many negative health results of alcohol abuse are fetal alcohol syndrome (FAS), and liver and other aerodigestive cancers. It is broadly believed that alcohol consumption and alcoholism lead to cancer and FAS, at least in part, via inhibition of synthesis of the transcription activator retinoic acid (RA) synthesis from retinol (vitamin A). A better understanding of the mechanism by which alcohol consumption leads to decreased RA production would be valuable for both prevention and amelioration of alcohol-associated disease. It is well established that ethanol directly competes with endogenous retinol for oxidation by several isoforms of alcohol dehydrogenase (ADH, EC 1.1.1.1). There is a widely-held, but unproven, theory that the ethanol-induced shifts in the levels of NADH also play a role in decreased oxidation of retinol by ADH. It has been difficult to design experiments to quantify the roles of the various inhibition mechanisms in retinol oxidation because inhibition is a cell system property rather than a phenomenon assignable to a single enzyme. We have developed a novel computational model of retinol oxidation that can be used to address inhibition in the context of several enzyme systems operating together to allow analysis and manipulation of the significant reactions encompassing ethanol and its interaction with retinol metabolism.

We hypothesize that the ethanol-induced NADH increase inhibits RA synthesis in liver cells by inhibition of aldehyde and alcohol dehydrogenases. This represents the novel mechanism by which ethanol may decrease RA synthesis. The NADH-oxidative capacity of susceptible tissue and the potential for ethanol oxidation (producing NADH) are both measurable risk factors for FASD/developmental toxicity and upper airway/GI cancers where alcohol may affect RA signaling. Furthermore, since oxidative stress is implicated as a risk factor contributing to the development of liver cancer, this hypothesis provides an additional mechanism by which elevated NADH levels contribute to the development of the disease state.

Summer Project:

1. Computational modeling of alcohol dehydrogenase and/or aldehyde dehydrogenase oxidation of retinol and retinaldedhye to retinoic acid in a system of reactions. Involves light programming in Python on LINUX
2. Purification from E. coli and characterization of alcohol dehydrogenase oxidation of retinol with in vitro enzyme assays.
3. Cell Culture manipulation to assess the impact of NADH elevation on retinol oxidation by ADH.  Also involves HPLC analysis of extracts. 

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Dr. Barry Myers

Northwest Nazarene University

Research:

Repeat elements are prolific and are estimated to account for 42% of the human genome and specifically, LINE-1 repeat elements (L1s) make up approximately 20% of the DNA of some mammals and at least 30% of human DNA. They have been implicated in disease onset. Research has shown that the distribution of L1s on the human X chromosome is significantly different than autosomes. Their evolutionary impact remains unclear, because no comparative survey of their distribution across several genomes has been done. In fact, several recent studies have pointed to the beneficial nature of comparing the human genome to non-mammalian vertebrates (e.g., fish) for detecting regulatory elements. It is possible that repeat elements, often referred to as junk DNA, may play an important role in genetic change. And since these areas of duplicated material may contain answers to complex disease traits, their locations, content, and distribution must be studied. The research question will be to explain the differences between mammalian and non-mammalian orders. This has health implications because transposition in humans has caused diseases, and if there is a transposition control mechanism in non-mammals then it could indicate a way to prevent this sort of disease.

Summer Project:

·         developing scripts to automate the access and maintenance of genome sequence databases locally

·         acquiring, installing, and learning to use software applications required to complete the analyses (e.g., RepeatMasker, Censor, gridMathematica, etc.)

·         comparing the outputs of the different repeat detection programs

·         comparing the distribution of repeat elements (such as L1s, ALUs, SINEs, etc.) on sex chromosomes versus autosomes across species

·         comparing the distribution of repeat elements (such as L1s, ALUs, SINEs, etc.) on sex chromosomes versus autosomes between classes

·         comparing the distribution of repeat elements (such as L1s, ALUs, SINEs, etc.) of a single chromosome across species

·         comparing the distribution of repeat elements (such as L1s, ALUs, SINEs, etc.) across chromosomes of varying arm length

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Dr. Ron Strohmeyer

Northwest Nazarene University

Biology

rwstrohmeyer@nnu.edu

Research:

Chronic brain inflammation has been studied in the Alzheimer’s disease brain for nearly two decades, characterizing numerous inflammatory proteins and toxic molecules, their effects on brain cells, and the brain cells producing them. Less well studied have been the controls within cells that regulate these processes. Cells control their expression of proteins by carefully regulating the expression of the genes encoding them via transcription factors.

Dr. Strohmeyer’s research interests are studying a transcription factor family that plays a central role in regulating several cellular programs of interest in Alzheimer’s disease. This family is known as the CCAAT/Enhancer Binding Proteins (C/EBPs) and is a family of six genes. Together and in combination with other types of transcription factors, C/EBPs help regulate cellular programs of energy metabolism, cell proliferation and differentiation, and inflammation. Though all are important areas in Alzheimer’s research, Dr. Strohmeyer is currently focusing on studying the role of C/EBPs in regulating the expression of inflammatory genes in microglia and astrocyte cells in the brain in Alzheimer's disease.

This research project encompasses four major objectives:

• Characterizing the expression pattern of each C/EBP isoform in human brain tissue and in brain cell cultures.

• Assessing the functionality of C/EBPs in modulating the expression of cytokine, chemokine, complement, iNOS, and other inflammatory genes.

• Assessing the role of C/EBPs in glial cell activation and differentiation in response to inflammatory stimuli and β-amyloid protein.

• Determining whether C/EBPs may be modulated by an anti-inflammatory signaling pathways triggered by cholesterol-lowering drugs collectively known as statins.

Summer Project:

Establish mouse microglia cell line (BV-2) and treat with amyloid, NSAIDs, and statins and measure C/EBP levels by western blot in these cultures under these treatment conditions.

Immunocytochemistry of BV-2 mouse microglia cells for each of the C/EBP isoforms under each of the conditions described above.

Development of IL-1, IL-6, and TNF-α ELISAs to measure these cytokines in BV-2 mouse microglia cultures under each of the conditions described above.

Immunohistochemistry in human brain sections for each of the C/EBP isoforms.

Western Blot assay of human brain protein extracts for each of the C/EBP isoforms.

Immunocytochemistry of BV-2 mouse microglia cells for each of the C/EBP isoforms.