Areas of Interests
- Research Interest
- Mechanism & Treatment of GI Ulcer Disease & Cancer
Mechanism & Treatment of GI Ulcer Disease & Cancer
The gastrointestinal (GI) mucosa is constituted by a population of highly differentiated epithelial cells that have secretary, absorptive and endocrine function. The luminal surface of these polarized epithelial cells, interfaces with a hostile proteolytic environment that will readily digest dietary nutrients. To prevent autolysis, the GI mucosa developed intricate barrier properties that prevent the back – diffusion of luminal acid, bacterial toxins and other agents (e.g. bile salts). This barrier property is compromised in disease states leading to peptic ulcer disease and other erosive diseases of the GI tract. Our laboratory has been studying the surface barrier properties of the stomach in health and disease states both in clinical tissue and in animal models of peptic ulcer disease and colitis. We have determined that the mucus gel layer of both the gastric and colonic mucosa have unique hydrophobic or non-wettable properties that protect the underlying tissue from noxious water-soluble agents in the lumen. Furthermore, we have demonstrated that this biophysical property is attributable to the ability of surface mucus cells to biosynthesize and secrete surfactant-like phospholipids (PLs) that recruit to the air/liquid interface of the mucus gel layer. We have also demonstrated that this hydrophobic PL layer is attenuated in conditions associated with peptic ulcer disease (intake of aspirin and other non-steroidal anti-inflammatory drugs/NSAIDs and infection with Helicobacter pylori) and colitis in both man and animal models. We are presently utilizing this information to develop strategies to fortify the barrier to treat/prevent peptic ulcer disease and inflammatory bowel disease. A start-up company, PLx Pharma Inc. was formed in 2003 to commercialize a novel class of NSAIDs that have been pre-associated with soy PLs to reduce the drugs’ GI toxicity. The first of these PL-associated drugs (PL2200 Aspirin) has recently received NDA regulatory approval by the FDA. A new focus of the Lichtenberger lab is to study the mechanism by which aspirin and related NSAIDs reduce the incidence and metastatic spread of cancer. Dr. Lichtenberger currently serves as Associate Director of the TMC-Digestive Diseases Center
- Zhou Y, Maxwell KN, Sezgin E, Lu M, Liang H, Hancock JF, Dial EJ, Lichtenberger LM, Levental I. (2013) Bile acids modulate signaling by functional perturbation of plasma membrane domains. J Biol Chem. 288(50):35660-70. doi: 10.1074/jbc.M113.519116. Epub 2013 Oct 28.
- Lim YJ, Dial EJ, Lichtenberger LM. (2013) Advent of novel phosphatidylcholine-associated nonsteroidal anti-inflammatory drugs with improved gastrointestinal safety. Gut Liver. 7(1):7-15. doi: 10.5009/gnl.2013.7.1.7. Epub 2012 Nov 13.
- Lichtenberger LM. (2013) Role of phospholipids in protection of the GI mucosa. Dig Dis Sci. 58(4):891-3. doi: 10.1007/s10620-012-2530-8.
- Lichtenberger LM, Zhou Y, Jayaraman V, Doyen JR, O’Neil RG, Dial EJ, Volk DE, Gorenstein DG, Boggara MB, Krishnamoorti R. (2012) Insight into NSAID-induced membrane alterations, pathogenesis and therapeutics: characterization of interaction of NSAIDs with phosphatidylcholine. Biochim Biophys Acta. 1821(7):994-1002. doi: 10.1016/j.bbalip.2012.04.002. Epub 2012 Apr 14.
- Lichtenberger LM, Phan T, Okabe S. (2011) Aspirin’s ability to induce intestinal injury in rats is dependent on bile and can be reversed if pre-associated with phosphatidylcholine. J Physiol Pharmacol. 62(4):491-6.
- Cryer B, Bhatt DL, Lanza FL, Dong JF, Lichtenberger LM, Marathi UK. (2011) Low-dose aspirin-induced ulceration is attenuated by aspirin-phosphatidylcholine: a randomized clinical trial. Am J Gastroenterol. 106(2):272-7. doi: 10.1038/ajg.2010.436. Epub 2010 Nov 16.