Research Assistant Professor Mohamed El-Zaatari, Ph.D., the initial GCF-American Gastroenterology Association Foundation grantee, has developed three different research proposals that are moving forward because of his initial grant support provided by the Gastric Cancer Foundation. Your support of the Foundation’s mission is making a difference.
Last year, after his initial investigations at the University of Michigan, Dr. El-Zaatari received more than half a million dollars in funding from the Department of Defense to pursue his studies. Many members of the military become susceptible to the H. pylori bacteria, which has a suspected link to the formation of gastric cancer. His initial research focuses on how precancerous lesions develop in the stomach and whether this can be prevented by targeting the gastric B cells with rituximab to disrupt the immune cell cycle that fuels the pre-cancerous lesions.
His second investigation is related to developing a technique to increase or decrease the infiltration of cytotoxic T cells into the inflamed stomach, and to study their characteristics. Cytotoxic T cells appear to play a central role in fueling gastric pre-cancerous lesions, but can also be targeted to kill cancer cells. Fine-tuning a technique to increase or decrease their infiltration will not only help understand their characteristics in pathology, but will also open avenues to allow these cells to reach their targets better if they are targeted to specific cancer cell types. One example where this would be useful is the combined use of chimeric antigen receptor T-cells (CARTs) therapy, which has been successful against blood cancers, but faces obstacles of low efficiency for the killer T cells to infiltrate solid organ tumors.
His third research project involves identifying how one specific immune cell population, called Myeloid-Derived Suppressor cells (MDSCs), cross-talks with the epithelial layer to regulate in gastric precancerous lesions.
Overall, these studies provide further understanding of the role of immune cells in gastric cancer development. However, one byproduct from these studies is that Dr. El-Zaatari is now able to generate transcriptional signatures of different immune sub-populations in the stomach, and how they talk to each other.
“I now have a blueprint of how immune cells are talking to each other and can draw maps to identify their conversations within the inflamed pre-cancerous stomach. This will generate an ‘immunome’, that is a group of transcriptional immunological blueprints that will better define disease context and what different roles the immune cells undertake” El-Zaatari says.
As the early supporters of the Foundation were convinced, if they can keep talented young investigators involved in gastric cancer rather than other higher profile cancers, this disease will get the attention it deserves by ambitious researchers.