[XNDA Roster]

The Xenobiotic and Nutrient Disposition and Action [XNDA] Study Section reviews applications related to the disposition (absorption, metabolism, distribution, and excretion) of supraphysiologic (SP) levels of nutrients and non-nutrient chemicals, including xenobiotics such as pro-drugs and drugs, biopharmaceutical agents, alcohol, phytochemicals/ botanicals, and other non-drug chemicals, and the study of their mechanisms of action (both pharmacological and toxicological) in normal and pathological conditions of the digestive system.

Studies that address the effects of digestive system-generated metabolites of xenobiotics on organ systems other than the digestive system may be considered in this Study Section. XNDA may also lend its expertise to the review of applications that address the metabolism and disposition of xenobiotic in other organs (e.g., lung, immune system, reproductive system, kidney) when the context of the applications are multi-organ effects.

Specific areas covered by XNDA:

• Gastrointestinal (including splenic/lymphatic) and/or hepatic disposition of nutrients (e.g., vitamins, minerals, amino acids, at supra-physiological levels), drugs (ranging from small molecules to biopharmaceuticals/macromolecules) and non-drug chemicals (including alcohol, metals, toxins, phytochemicals/botanicals and environmental toxicants), including processes of absorption. biotransformation, distribution and excretion. 
• In vitro and animal models that study xenobiotic disposition.
• Biotransformation including the phase I (e.g., oxidation), phase II (e.g., conjugation) and phase III (e.g., transport) processes. 
• Membrane processes related to xenobiotic and nutrient disposition, including passive, vesicular, receptor, and transporter-mediated processes (e.g., nutrient transporters, efflux transporters, MDR / MRPs, ion transport/channels). 
• Hepatic clearance processes as related to xenobiotics and SP nutrients, including perfusion, uptake, binding, biotransformation, and/or biliary excretion.
• The role of bile acids and lipids in xenobiotic disposition and/or toxicity.
• Interactions among xenobiotics (e.g., drug-drug interactions, and nutrient-drug interactions, alcohol-drug interactions), involving disposition and response processes.
• Role of genetics and genomics in disposition and effects of SP nutrients and xenobiotics (e.g., pharmacogenetics, pharmacogenomics, toxicogenetics, toxicogenomics).
• In vitro and animal models that investigate the molecular basis of 'gene-environment' interactions related to the digestive system, including studies focused on putative environmental susceptibility genes and/or pharmacogenetics.
• Role of physiological variation in disposition and action of xenobiotics and SP nutrients.
• Theoretical, mechanistic, and/or integrated studies of kinetics and/or dynamics of SP nutrients and xenobiotics (e.g., pharmacokinetics, pharmacodynamics, toxicokinetics and toxicodynamics).
• Mechanisms of action of xenobiotics and SP nutrients, including toxicological and/or pharmacological effects on the digestive system.
• Xenobiotic and SP nutrient-mediated alterations in signal transduction, cell cycle regulation, receptors, genes, apoptosis and/or oncosis (necrosis).
• Structure-function relationships for enzymes/transporters/receptors involved in SP nutrient and/or xenobiotic disposition and effects.
• Production, elimination and biological effects of reactive intermediates, including reactive oxygen species (e.g., oxidative stress), mediated by SP nutrients or xenobiotics.

XNDA has the following shared interests within the DIG IRG:

• With Gastrointestinal Cell and Molecular Biology [GCMB]:  Applications focusing on understanding fundamental processes/ pathways of dysplasia, neoplasia, mutagenesis and/or DNA repair, could be assigned to GCMB.  If the focus is on understanding the disposition and/or mechanisms of action of xenobiotics, or SP nutrients, the application could be assigned to XNDA.
  
  
• With Gastrointestinal Cell and Molecular Biology [GCMB]; Hepatobiliary Pathophysiology [HBPP]; and Gastrointestinal Mucosal Pathobiology [GMPB]:  There is shared interest in the area of oxidative stress with GCMB, HBPP and GMPB.   An application to evaluate the toxicological or pharmacological implications of xenobiotic-induced oxidative stress (production/elimination of reactive intermediates, including reactive oxygen and nitrogen) could be assigned to XNDA.  Where the focus is on oxidative stress related to infection or inflammation, it could be assigned to GMPB; where the focus is on the molecular and cellular processes that address endogenously-mediated oxidative stress, it could be assigned to GCMB.  Where the focus is on oxidative stress related to ischemia-reperfusion injury or other mechanisms of hepatic cell injury, it could be assigned to HBPP.
  
  
• With Hepatobiliary Pathophysiology [HBPP]:  (1) There is shared interest with HBPP in the area of biliary excretion.  Where the focus is on understanding the physiological aspects of biliary function, the application could be assigned to HBPP.  Where the focus is on biliary elimination of xenobiotics or alterations of xenobiotic disposition by the hepatobiliary system, the application could be assigned to XNDA. (2) There is shared interest in the area of alcohol metabolism and effects between HBPP and XNDA.  Where the focus of the application is on the disposition of alcohol or the effects of alcohol on the disposition of other xenobiotics, the application could be assigned to XNDA.  Where the focus is on the pathophysiology of alcohol-related liver disease, the application could be assigned to HBPP.
  
  
• With Clinical and Integrative Gastrointestinal Pathobiology [CIGP]:  (1) There is shared interest with CIGP in the area of gastrointestinal motility.  Applications with a focus on understanding the consequences of altered GI motility on xenobiotic disposition (absorption) could be assigned to XNDA.  All other studies related to GI motility could be assigned to CIGP.   (2) There is shared interest with CIGP in the area of 'gene-environment' interactions. Laboratory-based studies examining pathways involved in 'gene-environment' interactions, including in vitro and animal models, could be assigned to XNDA.  Gene-environment interaction studies focused on human populations (epidemiologic or patient based) could be assigned to CIGP.   Studies related to interactions of the microenvironment of the intestine and genes could be assigned to CIGP.  (3) There is shared interest in the area of alcohol metabolism and effects between CIGP and XNDA.  Where the focus of the application is on the disposition of alcohol, or the effects of alcohol on the disposition of other xenobiotics, the application could be assigned to XNDA.  Where the focus is on the pathophysiology of alcohol-related pancreatic or intestinal disorders, the application could be assigned to CIGP.

XNDA has the following shared interests outside the DIG IRG:

• With the Biological Chemistry and Macromolecular Biophysics [BCMB] IRG:  Shared interest exists for structure-function relationships for enzymes/transporters/receptors involved in nutrient and/or xenobiotic disposition.  Where interests are focused primarily on structure-function relationships of enzymes, transporters and/or receptors for xenobiotics and nutrients in the digestive system, they could be assigned to the XNDA.  Studies designed to address general principles of enzymes, transporters and/or receptors may be considered under the auspices of the BCMB IRG.  Shared interests also exist in the study of pro-drugs. Studies focused primarily on the disposition and action of the pro-drug in the digestive system could be assigned to XNDA.  In general, studies of pro-drug structure and function that use primarily biophysical techniques (e.g., X-ray diffraction, electron spin resonance, and single molecular techniques) could be assigned to the BCMB IRG.
  
• With the Bioengineering Sciences and Technologies [BST] IRG: Shared interests exist for mathematical modeling.  Studies focused on mechanisms and applications in xenobiotic or nutrient (at supraphysiological levels) transport, pharmacokinetics, pharmacodynamics and toxicodynamics could be assigned to XNDA.  Studies focused on developing mathematical modeling methods could be assigned to the BST IRG.  Applications focused on GI specific biological mechanisms and therapies could be assigned to XNDA. Applications focused on developing technologies to introduce genes and drugs in a general cellular context could be assigned to the BST IRG.
  
• With the Immunology [IMM] IRG: There is shared interest with IMM in studies involving xenobiotics used to diagnose or treat immunological disorders and diseases.  Studies on the mechanisms of action or efficacy of pharmaceutical agents used in the diagnosis or treatment of immune disorders or diseases may be appropriate for IMM.  Similar studies of the use or action of immunological adjuvants may also be appropriate for IMM.  Applications where the primary focus is on the disposition (absorption, metabolism, distribution, and excretion) of xenobiotics, including pharmaceutical agents may be appropriate for the DIG IRG.
  
• With the Infectious Diseases and Microbiology [IDM] IRG: When the emphasis is on the evaluation of the therapeutic mechanisms of action of novel agents that are potentially useful against infectious diseases, assignment to the IDM IRG may be appropriate.  Applications where the primary focus is on the disposition (absorption, metabolism, distribution, and excretion) of xenobiotics, including pharmaceutical agents, or their toxicological effects on the host, may be appropriate for the DIG IRG.
  
• With the Oncological Sciences [ONC] IRG:  Shared interests exist in the area of drug/ biopharmaceutical development for cancer treatment including chemotherapy.  When the emphasis is on the development and testing of cancer therapeutics, ONC IRG is appropriate. However, XNDA should be considered for applications related to GI toxicity of cancer therapeutics.
  
• With the Cardiovascular Sciences [CVS] IRG: Studies that examine arrhythmias due to administration of therapeutic agents may be assigned to the CVS IRG.   Applications that focus on the general disposition of pro-drugs and drugs or biopharmaceutical agents may be assigned to XNDA.
  
• With the Endocrinology, Metabolism, Nutrition and Reproductive Sciences [EMNR] IRG: Shared interests exist in areas of xenobiotic and/or nutrient metabolism, and toxicology.  Studies could be assigned to XNDA when the kinetics and mechanism pertain to xenobiotics and nutrients utilized at therapeutic and/or toxicological doses. On the other hand, applications dealing with metabolic aspects of nutrients or food components, once absorbed and available to non-digestive system tissues and cells, could be assigned to the EMNR IRG.  Basic or clinical studies that place a major emphasis on nutrients, xenobiotics, and endocrine disruptors and their action with endocrine systems may be assigned to the EMNR IRG.  However, when interactions with the endocrine system are not the primary focus, assignment should be made to XNDA.
  
• With the Respiratory Sciences [RES] IRG: Shared interests exist in areas such as the disposition and action of drugs and other foreign materials when taken into the body.  Studies could be directed to XNDA when they address the effects of digestive system-generated metabolites of xenobiotics or the absorption and excretion of xenobiotics by the digestive system or where multiple organ systems are involved or where the hepatic and /or gastrointestinal activities dominate.  Applications that address the metabolism and disposition of xenobiotics in the lung may be assigned to the RES IRG.  Environmental and occupational lung diseases (including interstitial lung diseases and asthma induced by environmental agents) and inhalation and respiratory toxicology, including the effects of particles and gasses, including drugs, on lung cells, may also be assigned to the RES IRG.
  
• With the Renal and Urological Sciences [RUS] IRG:  Shared interests exist in areas such as renal transport mechanisms and drug therapy.  Studies could be assigned to XNDA when the kinetics, dynamics and mechanisms address disposition and effects of drugs where multiple organ systems are involved, or where the hepatic and/or gastrointestinal activities dominate. Pharmacology relating to kidney function and toxic injury to the kidney, including xenobiotic-mediated alterations in renal signal transduction, cell-cycle regulation, receptors, genes, and apoptosis; as well as mechanisms of renal apoptosis and necrosis, senescence, genotoxic responses, DNA damage, oxidative stress, and cellular aging could be assigned to the RUS IRG.
  
• With the Surgical Sciences, Biomedical Imaging and Bioengineering [SBIB] IRG:  Studies of the pharmacodynamics and pharmacokinetics, including toxicology, of general or local anesthetic agents may be assigned to SBIB.  Studies of bioengineering approaches to facilitate drug delivery and studies of the use of biomaterials to modify drug delivery should be considered for assignment to SBIB.  General studies of the disposition of xenobiotics, biopharmaceutical agents, phytochemicals/ botanicals, and other non-drug chemicals, and the study of their mechanisms of action, particularly when they relate to normal and pathological conditions of the digestive system, may be assigned to XNDA.
   
• With the Integrative, Functional and Cognitive Neuroscience [IFCN] IRG: Shared interests exist in areas where the pharmacological and/or toxicological effects of xenobiotics, including alcohol, on the nervous system are studied.  Where studies relate primarily to the disposition of such xenobiotics, or toxicity to the digestive system, they could be assigned to XNDA.  Where studies of xenobiotics relate primarily to effects on the nervous system, they could be assigned to the IFCN IRG.