Membrane Biology Lab
Key investigator
Elizabeth Marcus, MD
Associate Professor, Department of Pediatrics
Fellowship Program Director, Pediatric Gastroenterology, Hepatology, and Nutrition
David Geffen School of Medicine at UCLA
Dr. Marcus has a BA in psychology from Stanford University and an MD from the Keck School of Medicine at USC. She completed residency in pediatrics at Children’s Hospital Los Angeles and fellowship in pediatric gastroenterology, hepatology, and nutrition at UCLA. She has been a faculty member in the Department of Pediatrics since completing fellowship. Her research focus is on the gastric pathogen Helicobacter pylori.
Lab members
- Keith Munson, PhD
- Elmira Tokhtaeva, PhD
- Olga Vagin, PhD
Funding
- NIH-NIDDK
- UCLA Goodman Luskin Microbiome Center - Microbiome Vaccine Program
- Children's Discovery and Innovation Institute
Current research focus
- Acid acclimation of H. pylori and identification of potential therapeutic targets
- H. pylori is a neutralophile yet is able to survive in the acidic gastric environment via adjustment of the pH of the periplasmic space. UreI, an inner-membrane localized, pH gated urea channel, opens in response to a drop in media pH, allowing urea access to cytoplasmic urease enzyme, which traffics to the channel. Urea breakdown to carbon dioxide and ammonia is catalyzed by urease enzyme, and these products buffer the periplasmic space to a pH in the range of survival and growth of a neutralophile. This system of acid acclimation has several unique components that are being studied as potential drug targets, to help mitigate the issues of antibiotic resistance and compliance that plague current treatment regimens.
- Mechanisms of gastric injury by H. pylori
- H. pylori interferes with the integrity of the gastric epithelium, leading to the possibility of advanced gastric disease. The Na,K-ATPase is a critical eukaryotic transport enzyme required to maintain sodium gradients and also has an important role in cell junctions. We have shown that H. pylori interferes with BiP-mediated folding of newly synthesized α and β subunits of Na,K-ATPase in the endoplasmic reticulum (ER), leading to ubiquitylation and proteasomal degradation of these subunits before they can be packaged and trafficked to the membrane. The end result is less Na,K-ATPase in the basolateral membrane of gastric epithelial cells in both acute and chronic infection models and decreased barrier function of the epithelial layer. This work is currently being expanded to examine additional pathways of gastric injury related to ER lectin mediated protein quality control, cell migration, division, adhesion, and wound healing.
Publications
Founding director
George Sachs, DSc, MD (Memorium: November 12, 2019) is best known for his studies of the biochemistry and biology of the gastric H+,K+-ATPase. He showed that acid secretion by the stomach is due to an electro-neutral ATP-dependent pump, the H+-K+-ATPase. Based on this discovery, he helped to develop drugs, the PPIs, that specifically targeted this pump. These drugs are now the mainstay of treatment of peptic ulcer disease and gastro-esophageal reflux disease. Dr. Sachs has received many honors and awards, including the William Beaumont Prize in Gastroenterology, the Hoffman LaRoche Award, the William S. Middleton Award, the Janssen Award for Special Achievement in Gastroenterology and the Gairdner Foundation Award. He wrote more than 375 peer-reviewed articles, 76 reviews, 32 book chapters, and 8 books.