Current Projects
National Institutes of Health RO1 DK061568
Cysteine, Intestinal Thiols, and Goblet Cell Development
HR Gaskins (PI); Co-investigator: Sharon Donovan
Tests the hypothesis that the lack of luminal cysteine is a primary insult perceived by the parenterally nourished intestinal epithelium, and that the functional endpoint of this nutritional deficiency is a more oxidized intracellular redox potential, leading to goblet cell expansion. Thus, we propose that mucus-producing goblet cells are guardians of mucosal redox homeostasis.
National Institutes of Health R21 EB004513
Engineered Platforms to Control Intracellular Redox
PJA Kenis (Co-PI) Chemical & Biomolecular Engineering; Co-PI: HR Gaskins
This project focuses on the design and validation of: 1) Engineered electrochemical platforms for cell studies that permit precise control of the intracellular redox environment; and 2) FRET-based redox biosensors that permit visual monitoring of intracellular and intraorganellar redox potentials.
Carle UIUC Translational Research Program
Genetic Variation in Mucosal Defense and Inflammatory Bowel Disease
HR Gaskins (PI); Co-Investigators: Eugene Greenberg, Carle Foundation Hosptial; Steve Blanke, Rod Mackie, Richard Tapping, Sheng Zhong
A clinical study in which patients presenting with Crohn's disease will be compared with appropriately matched controls to determine if defined clinical features of IBD and/or individual colonic microbiota signatures are associated with: 1) common allelic or functional variants of genes encoding pattern recognition receptors; 2) allelic variants of goblet cell-specific genes; and 3) specific mucin chemotypes; or with 4) some combination of these variables.
General Mills Bell Institute for Health and Nutrition
Toward an Understanding of Interindividual Variation in Microbial Mechanisms of Hydrogen Disposal and Colonic Health
HR Gaskins (PI); Co-Investigator: RI Mackie
This study focuses on the design and validation of molecular probes that target both the 16S rRNA gene as a phylogenetic marker and genes encoding biochemical pathways uniquely expressed by two major groups of hydrogenotrophic microbes associated with the colonic mucosa of humans, sulfate reducing bacteria and methanogenic archaea.
Bristol-Myers Squibb Freedom to Discover Nutrition Research Grant
Defining the Nutritional Requirements of the Developing Intestinal Ecosystem
SM Donovan (PI); Co-Investigators: George Fahey, Peter Garlick, Rex Gaskins, Rod Mackie, Larry Schook, Kelly Swanson, Kelly Tappenden, Bryan White
This project focuses on the use of the neonatal pig as a model to study the influence of the intestinal microbiota on the nutritional status of newborns (premature births). Cloned newborn piglets that are colonized with various bacterial mixtures are used to determine the influence of host genotype on colonization and nutritional needs.
Representative Publications
Huycke MM, Gaskins HR (2004) Commensal bacteria, redox stress, and colorectal cancer: Mechanisms and models. Exp Biol Med 229(7):586-597.
Conour JE, Graham WV, Gaskins HR (2004) A combined in vitro/bioinformatic investigation of redox regulatory mechanisms governing cell cycle progression. Physiol Genomics 18(2):196-205.
Graham WV, Tcheng DK, Shirk AL, Attene-Ramos MS, Welge ME, Gaskins HR (2004) Phylomat: an automated protein motif analysis tool for phylogenomics. J Proteome Res 3(6):1289-1291.
Attene-Ramos MS, Kitiphongspattana K, Ishii-Schrade KB, Gaskins HR (2005) Temporal changes of multiple redox couples from proliferation to growth arrest in IEC-6 intestinal epithelial cells. Am J Physiol Cell Physiol 289(5):C1220-1228.
Attene-Ramos MS, Wagner ED, Plew MJ, Gaskins HR (2006) Evidence that hydrogen sulfide is a genotoxic agent. Mol Cancer Res 4(1):9-14.
Attene-Ramos MS, Wagner ED, Gaskins HR, Plewa MJ (2007) Hydrogen sulfide induces direct radical associated DNA damage. Mol Cancer Res 5(5):455-9.
Chowdhury SR, King DE, Willing BP, Band MR, Beever JE, Lane AB, Loor JJ, Marini JC, Rund LA, Schook LB, Van Kessel AG, Gaskins HR (2007) Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets. BMC Genomics 8(1):215.
Kolossov VL, Spring B, Sokolowski A, Conour JE, Clegg RM, Kenis PJA, Gaskins HR (2008) Engineering redox-sensitive linkers for genetically encoded FRET-based biosensors. Exp Biol Med 233(2): 238-48.
Congdon CB, Aman J, Nava GM, Gaskins HR, Mattingly C (2007) An evaluation of information content as a metric for the inference of putative conserved noncoding regions in DNA sequence using a genetic algorithms approach. IEEE/ACM Trans Comput Biol Bioinform 5(1):1-14.
Recent Meetings and Abstracts
Experimental Biology 2008
Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis
GM Nava, DY Lee, SY Cai, JL Boyer, A Hernández-Zavala, DJ Thomas, HR GaskinsToxicogenomic analysis of human intestinal epithelial FHs 74 Int cell responsiveness to sulfide
MS Attene-Ramos, GM Nava, MG Muellner, E Wagner, M Plewa, HR Gaskins
Experimental Biology 2007
Genomic analysis of glutathione biosynthesis and metabolism in the invertebrate chordate Ciona intestinalis
GM Nava, JH Ospina, HR GaskinsPolarized provision of cysteine affects glutathione biosynthesis without impacting gene expression pathways responsive to oxidative stress in intestinal epithelial cells
SR Chowdhury, JE Conour, HR GaskinsHydrogen sulfide induces direct radical associated DNA damage
HR Gaskins, MS Attene-Ramos, ED Wagner, MJ Plewa
Supplemental Data
Redox-regulated Cell Cycle Proteins: Redox Motif List
