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Research Interests

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Last updated, Feb. 1, 2016

Research Interests


   Small-intestine epithelial cells are the primary site of absorption of nutrients such as glucose and amino acids. Absorption through the intestine requires such molecules to cross two distinct membranes: (1) take up by the epithelial cells from the lumen across the brush-border membranes (BBMs), (2) followed by transfer to the blood across the basolateral membranes. Pancreatic proteases, small brush-border proteases, and peptidases digest proteins of dietary or endogeneous origin to release short-chain peptides and free amino acids. A growing body of scientific evidence in the past decade has revealed that many food proteins and peptides exhibit specific biological activities in addition to their established nutritional value. Bioactive peptides are specific protein fragments that positively impact body function or condition and ultimately may influence human health. These peptides include opioid, hypotensive, mineral-absorption stimulating, anticoagulative, and immunomodulatory types.
My primary research interest is molecular approaches to the study of structure-function relationships of egg and milk derived bioactive proteins/peptides and egg allergy, to enhance human intestinal health. The egg is the largest biological cell known which originates from one cell division and is composed of various important chemical substances that form the basis of life. Therefore, the avian egg is considered to be a store-house of nutrients such as proteins, lipids, enzymes and various biologically active substances including growth promoting factors and defences against bacterial and viral invasion. Milk is also recognized as containing an array of bioactiveties that dramatically extended the range of influenced of mother over young beyond simple nutrition. Our group is characterizing the biophysiological functions of egg and milk components and seeking novel biologically active substances. Egg and milk proteins have numerous potential for releasing biologically functional peptides due to degradation by pepsin, trypsin or chymotrypsin in the gut. My group is studying 3 major functions of anti-tissue oxidative stress, anti-inflammatory and immunomodulatory functions. Food allergy is a major human health concern. My lab is working on the fine mapping of allergenic epitopes of ovomucoid and ovalbumin, dominant allergens of egg white and structure-function studies of allergenic proteins using site-directed mutagenesis and genetic glycosylation for engineering food allergens to design hypoallergenic variants for specific immunotherapy (SIT). We are also studying a mechanism of intestinal transportation of food allergens across epithelial cells and examining effective anti-allergenic agents from natural foods to prevent such allergic reactions as well as a mechanism of epithelial transport of bioactive peptides.

 

Current Research Projects

  1. Food allergy (molecular allergology of egg allergens)
  2. Anti-tissue oxidative stress peptides/amino acids
  3. Enhancement of mucosal immune system
  4. Anti-inflammatory peptides/amino acids
  5. Intestinal absorption of egg allergens and bioactive peptides.

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Food allergy


(Mucosal allergic sensitization and reactions)

Food allergy is one of the most problematic issues of health concerns. Our laboratory is examining molecular approaches to the studies of egg allergens to answer the question "What makes an allergen and why?" and to develop novel approaches to prevent egg allergy.

Current Research Projects

  1. Molecular allergology of egg allergens (Ovomucoid and Ovalbumin)
  2. Anti-allergic agents from natural agents.
  3. Mechanism of antigen transportation across the human intestinal epithelial cells.
  4. Effect of probiotics on the modulation of allergic reactions.
  5. Modulation of Th1/Th2 associated cytokines and T-regulatory cells

 




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Anti-tissue oxidative stress and anti-inflammatory peptides/amino acids

Oxidative stress occurs when the production of damaging free radicals and other oxidative molecules exceeds the capacity of the body's antioxidant defences to detoxify them. The gut inflammatory response is a highly regulated physiological process that is critically important. Thus, gut oxidative stress and inflammatory damages are underlying factors implicated in the cause of a vast variety of human disorders, including cardiovascular disease, cancer, neurological disorders, diabetes, inflammatory diseases, and ischemia-reperfusion, as well as in the ageing process Our lab is exploring in finding natural bio-functional peptides and amino acids and its mechanism of cell signaling and regulation of transcriptional factors. Our lab is using nutrigenomic and proteomics approaches to achieve our goals.


Current Research Projects

  1. Anti-inflammatory/oxidative stress peptides in egg/milk proteins
  2. Functional amino acids
  3. Mechanism of cell signaling and regulation of transcriptional factors

 

Enhancement of Mucosal Innate Immune System


The mucosal immune system plays an important defensive role against luminal antigens (toxins, pathogenic bacteria, viruses, etc) to prevent their interaction with the epithelial surface. In addition to host-derived mechanisms of defense, we are interested in food-derived peptides that have an impact to modulate the mucosal immune system.

Current Research Projects

  1. Egg and milk derived immunomodulatory peptides.
  2. Structure-function studies of these peptides
  3. Innate immunity of food derived bioactive peptides.


Nat Rev Microbiol. (2004) 2:747-765

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Intestinal absorption of egg allergens and bioactive peptides.

The small intestinal mucosa is a layer of epithelia compartmentalized into villi and crypt regions. The transepithelial transport of oligopeptides across intestinal epithelial cells has attracted considerable interest in investigations into how biologically active peptides express diverse physiological functions in the body. There are three possible mechanisms for the intestinal transport of oligopeptides: (1) PEP 1-mediated transcellular transport for di- and tripeptides, (2) a transcytotic route, which is known to be used for the transport of macromolecules such as proteins, and (3) intracellular passive transport for peptide absorption. However, the role of these pathways in intestinal oligopeptide absorption is not yet fully understood, with the mechanism for oligopeptide transport across the intestinal epithelial apical membrane still being obscure. Our lab is exploring the research to understand the mechanism of transport of bioactive peptides and egg allergens. We use molecular and biochemical approaches to achieve these goals.

Current Research Projects

  1. PEP-1 mediated transcelluar transport of bioactive peptides and its cell signaling.
  2. Egg allergen transport across the intestinal epithelial cells and its impact on mucosal immunity.
  3. Food factors-gene interaction in regulating peptide transporter.

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Role of the Extracellular Calcium-sensing Receptor in Chronic Inflammatory Diseases

The extracellular calcium-sensing receptor (CaSR) is a class C G-protein coupled receptor (GPCR) and it plays a key role in the regulation of extracellular Ca2+ homeostasis in mammals. CaSR is widely distributed in diverse cell types in various tissues including the parathyroid, brain, kidney, lung and bone marrow, where it regulates cellular activities including secretion, apoptosis, proliferation, differentiation and ion-channel activity. It is also present in the gastrointestinal tract, and its activation has been shown to promote intestinal homeostasis, suggesting that CaSR may be a promising target for novel therapies to prevent chronic intestinal inflammation such as inflammatory bowel disease (IBD).

Current Research Projects

  1. Anti-inflammatory activity of ?-glutamyl cysteine (?-EC) and ?-glutamyl valine (?-EV) in intestinal inflammation in a mouse model of colitis.
  2. The CaSR-mediated anti-inflammatory effects of g-EV/EC and cross talking with the TNF-? receptor (TNFR).


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