+publisher:"Penn State University" +contributor:("Scott Brian Selleck, Committee Member")

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Penn State University

1. Wang, Wenqing. Tissue specific effects of NAD+ biosynthesis on muscle function, fat metabolism and gonad development in Caenorhabditis elegans.

Degree: 2014, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/23632

Both acting as a cofactor in diverse biochemical reactions, and as an obligate co-substrate for NAD+ consumers which regulate a number of key cellular processes, nicotinamide adenine dinucleotide (NAD+) is a critical molecule in cellular metabolism. Our lab has established an excellent C. elegans model system to study the developmental roles of NAD+ biosynthesis. Mutation in the C. elegans nicotinamidase PNC-1, the first enzyme in NAD+ salvage biosynthesis from nicotinamide (NAM) causes a spectrum of developmental defects, which are separately related to the PNC-1 biological function of NAM clearance or NAD+ production. In my study, I investigated the tissue specific defects on muscle functions, fat metabolism and gonad development caused by defective NAD+ biosynthesis. Because the live bacterial diet provides NAD+ precursors and possibility NAD+ to support C. elegans growth, the NAD+ biosynthesis defective pnc-1 mutants are more susceptible to dietary changes, and low quality diet induces abnormal fat accumulation and exacerbates gonad developmental delay in pnc-1 mutants. I used a metabolomics approach to gain a comprehensive understanding of the effect of defective NAD+ biosynthesis on global metabolism. Although blocking NAD+ salvage from NAM only moderately depletes NAD+ in pnc-1 mutants, it leaves a broad impact on metabolism. Metabolomics data have shown that glycolysis is defective in pnc-1 mutants, which as works of my colleagues pointed out, may be an underlying cause of pnc-1 gonad developmental defects. Besides NAD+ salvage biosynthesis from NAM, salvage from nicotinamide riboside (NR) and de novo NAD+ biosynthesis from tryptophan also contribute to building the NAD+ reservoir in C. elegans. Interestingly, a key enzyme in the de novo NAD+ synthesis pathway is absent from C. elegans genome, nonetheless, metabolites in de novo pathway functions as NAD+ precursors in promoting gonad development. Although endogenous NR salvage and de novo NAD+ biosynthesis are not the major NAD+ source in C. elegans, their activities are important for body wall muscle functions when NAM salvage is compromised. In summary, my work has expanded our knowledge of how NAD+ biosynthesis regulates physiological processes via modulation of NAM and NAD+ levels. I have demonstrated the tissue specific contributions made by different NAD+ biosynthesis pathways. The established metabolomics profile of pnc-1 mutants provides insights into its influence on global metabolism, and my work will help to decipher how metabolic perturbations lead to developmental and physiological consequences. Advisors/Committee Members: Wendy Hanna Rose, Committee Chair/Co-Chair, Melissa Rolls, Committee Member, Lorraine C Santy, Committee Member, Scott Brian Selleck, Committee Member, Ramesh Ramachandran, Committee Member.

Subjects/Keywords: NAD+; vitamin B3; nicotinamidase; nicotinamide riboside; quinolinic acid; metabolomics; glucose metabolism; lipid metabolism

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wang, W. (2014). Tissue specific effects of NAD+ biosynthesis on muscle function, fat metabolism and gonad development in Caenorhabditis elegans. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/23632

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wang, Wenqing. “Tissue specific effects of NAD+ biosynthesis on muscle function, fat metabolism and gonad development in Caenorhabditis elegans.” 2014. Thesis, Penn State University. Accessed April 15, 2021. https://submit-etda.libraries.psu.edu/catalog/23632.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wang, Wenqing. “Tissue specific effects of NAD+ biosynthesis on muscle function, fat metabolism and gonad development in Caenorhabditis elegans.” 2014. Web. 15 Apr 2021.

Vancouver:

Wang W. Tissue specific effects of NAD+ biosynthesis on muscle function, fat metabolism and gonad development in Caenorhabditis elegans. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Apr 15]. Available from: https://submit-etda.libraries.psu.edu/catalog/23632.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang W. Tissue specific effects of NAD+ biosynthesis on muscle function, fat metabolism and gonad development in Caenorhabditis elegans. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/23632

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

2. Hall, Molly Ann. Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits.

Degree: 2015, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/26751

Genome-wide association studies (GWAS) have identified numerous loci associated with human phenotypes. This approach, however, does not consider the richly diverse and complex environment with which humans interact throughout the life course, nor does it allow for interrelationships among genetic loci and across traits. Methods that embrace pleiotropy (the effect of one locus on more than one trait), gene-environment (GxE) and gene-gene (GxG) interactions will further unveil the impact of alterations in biological pathways and identify genes that are only involved with disease in the context of the environment. This valuable information can be used to assess personal risk and choose the most appropriate medical interventions based on an individual’s genotype and environment. Additionally, a richer picture of the genetic and environmental aspects that impact complex disease will inform environmental regulations to protect vulnerable populations. Three key limitations of GWAS lead to an inability to robustly model trait prediction in a manner that reflects biological complexity: 1) GWAS explore traits in isolation, one phenotype at a time, preventing investigators from uncovering relationships that exist among multiple traits; 2) GWAS do not account for the exposome; rather, they simply explore the effect of genetic loci on an outcome; and 3) GWAS do not allow for interactions between genetic loci, despite the complexity that exists in biology. The aims described in this dissertation address these limitations. Methods employed in each aim have the potential to: uncover genetic interactions, unveil complex biology behind phenotype networks, inform public policy decisions concerning environmental exposures, and ultimately assess individual disease-risk. Advisors/Committee Members: Marylyn Deriggi Ritchie, Dissertation Advisor/Co-Advisor, Marylyn Deriggi Ritchie, Committee Chair/Co-Chair, Santhosh Girirajan, Committee Chair/Co-Chair, Scott Brian Selleck, Committee Member, Ross Cameron Hardison, Committee Member, George H Perry, Committee Member, Catherine Mc Carty, Special Member.

Subjects/Keywords: gene-gene interactions; epistasis; PheWAS; phenome; EWAS; exposome; gene-environment interactions; complex traits

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hall, M. A. (2015). Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/26751

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hall, Molly Ann. “Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits.” 2015. Thesis, Penn State University. Accessed April 15, 2021. https://submit-etda.libraries.psu.edu/catalog/26751.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hall, Molly Ann. “Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits.” 2015. Web. 15 Apr 2021.

Vancouver:

Hall MA. Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Apr 15]. Available from: https://submit-etda.libraries.psu.edu/catalog/26751.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hall MA. Beyond genome-wide association studies (GWAS): Emerging methods for investigating complex associations for common traits. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/26751

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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