PROJECT SUMMARY / ABSTRACT
This K01 application proposes a ¿ve-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-certi¿ed 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
signi¿cant role in characterizing paligenosis, a process that di¿erentiated 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 o¿ce space for Dr. Cho. BCM
provides fully supported animal research facilities and 26 core facilities. BCM is also a¿liated 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 di¿erentiated 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 di¿erentiated
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 ¿elds 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 di¿erentiated 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 ¿elds around the world, which is another essential element for Dr. Cho to succeed
in the ribosome ¿eld. 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.