THE ROLE OF RIBOSOMES IN METAPLASIA IN THE GASTROINTESTINAL TRACT - PROJECT SUMMARY / ABSTRACT This K01 application proposes a five-year career development and research program focused on determining how ribosomes are regulated during zymogenic cell (ZC) metaplasia and how this process plays a critical role in regeneration and tumorigenesis. Candidate: Charles J. Cho, M.D., Ph.D., is an instructor in the Section of Gastroenterology and Hepatology, Department of Medicine at Baylor College of Medicine (BCM). Dr. Cho’s background includes 14 years of training and practice as a board-certified gastroenterologist in South Korea, where he gained extensive experience performing gastrointestinal endoscopy procedures. Since completing his clinical and Ph.D. training, Dr. Cho has worked in the laboratory of Dr. Jason Mills, where he has played a significant role in characterizing paligenosis, a process that differentiated cells such as ZCs use to reenter the cell cycle and fuel regeneration. Environment: The Mills Lab at BCM includes dedicated rooms for confocal microscopy, cell culture, and histology in addition to bench space and private office space for Dr. Cho. BCM provides fully supported animal research facilities and 26 core facilities. BCM is also affiliated with the Texas Medical Center, which provides further resources including the NIDDK P30 Digestive Diseases Center and its additional core facilities that will be used in the proposed work. Research Project: The proposed research is based on the hypothesis that temporal and spatial regulation of ribosomes is a core component of the ZC injury response, also known as paligenosis, that results in metaplasia and ultimately, carcinogenesis. Two aims are proposed to address this hypothesis: 1) Determine the regulatory mechanism of ribosomes required during the initial catabolic phase of paligenosis; and 2) Determine the role of ribosome biogenesis for cell-cycle reentry and restorative regeneration. Since ribosome biogenesis, maintenance, and translation in differentiated cells has been understudied, particularly in vivo, completion of these aims will create new knowledge of importance to the emerging concept of paligenosis, which may be applicable to the general response of differentiated cells in the gastrointestinal (GI) tract to stress. Career Development Plan and Goals: The members of the research advisory committee are each world-leading experts in a variety of fields related to the proposed aims, from ribosomes and translation to pancreatic carcinogenesis. The mentorship they will provide along with the protected research time will provide an essential research foundation for Dr. Cho to establish his own indepen- dent lab with a focus on the ribosome and translation in a generalized differentiated cell model. The training will also include participation in a diverse seminar series and national and international meetings that will provide opportunities to give presentations, interact with visiting outside speakers, and network with people in the gas- troenterology and ribosome fields around the world, which is another essential element for Dr. Cho to succeed in the ribosome field. The training provided by this support uniquely positions Dr. Cho to develop an indepen- dent R01-funded medical research program before transitioning to a principal investigator.
