Targeting B Cell-Mediated Type II Autoimmunity in Gastric Carcinogenesis
Abstract
Rationale: A cancer-causing pathogen, called Helicobacter pylori, is widespread in military destinations (usually developing countries) and has the potential to infect military personnel while on active duty. This pathogen considerably increases the risk of stomach cancer. In contrast to the U.S. where it is less common, it is widely present in Iraq, for example, where it can be detected in the drinking water. A similar situation exists in Afghanistan, and similarly in potential future military destinations. This pathogen causes long-term inflammation in the stomach, which can progress to stomach cancer. Eradicating this pathogen after initial infection may not reduce the cancer risk once the development of pre-cancerous lesions occurs. Therefore, this pathogen appears to trigger a series of events that may not be reversible in the stomach, which pose a risk for stomach cancer. Therefore, reducing the body?s inflammation caused by this pathogen is important to alleviate the outcome and reduce the cancer risk, especially in patients who show evidence of pre-cancerous development. Scientific Objective: We have identified an autoimmune mechanism, in which the body?s immune system attacks its own cells, as an underlying cause of stomach pre-cancerous lesions in mouse models. Our objective is to establish the autoimmune basis for this gastric pre-cancerous development, as a starting point towards proposing new management strategies in the future. The identification of autoimmunity as a cause for pre-cancerous lesions in the stomach will unravel new ideas on how to approach and manage this disease. This is important since the management of this disease provides a preventative strategy that reduces the risk of stomach cancer. Principal Investigator?s (PI?s) Career Goals in Cancer Research: The PI aims to develop a lifelong career in cancer research. This goal stems from a passion for discovery, and a passion for wanting to alleviate the suffering of cancer patients. The PI has spent the past 13 years developing his skills in studying stomach pre-cancerous and cancerous development. This spanned the period of his PhD, postdoctoral training, and faculty appointment. For this purpose, it is necessary for the PI to bridge the financial gap that will allow him to become a fully independent investigator. Being fully independent and in charge of an autonomous lab usually requires larger independent investigative grants (e.g., National Institutes of Health [NIH] R01s, Department of Defense [DoD], Department of Veterans Affairs [VA] merit awards). These grants are highly competitive and require well-established preliminary projects to be competitive and successful in attaining funding. Hence, this DoD Career Development grant is absolutely critical to provide the resources for building the PI?s initial core project. The PI has already demonstrated a milestone achievement by securing one smaller grant, which is currently contributing to building his project. The second milestone of attaining the DoD grant will be sufficient to propel the PI to compete for larger independent funding in order to establish independence. It will also provide the PI with sufficient resources to freely operate in the mere pursuit of discovery. Competition for funding is therefore a critical element towards the PI?s goal for discovery. The PI plans to undertake an innovative approach for reducing the risk of stomach cancer. Currently, the inflammatory components that fuel the transition from precancerous lesions to cancer are not fully understood. The PI therefore plans to study stomach cancer progression from the standpoint of inflammation, to unravel new avenues for treatment. Therefore, while the short-term goal is to establish the role of autoimmunity in fueling gastric pre-cancerous lesions and to propose preventative strategies, the long-term goal is to develop an independent career focusing on the immunological aspect of gastr
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710496
Entities
People
- Mohamad El Zaatari
Organizations
- United States Army
- University of Michigan