PROJECT SUMMARY / ABSTRACT
This K08 application proposes a ¿ve-year career development and research program focused on elucidat-
ing the transcriptional determinants and molecular heterogeneity of Barrett’s esophagus (BE). The applicant,
Ramon Jin, M.D., Ph.D., is a physician-scientist and an Instructor in Medicine in the Section of Hematology and
Oncology, Department of Medicine, at Baylor College of Medicine (BCM). Since completing his hematology and
oncology fellowship as a chief fellow, Dr. Jin has worked in the laboratory of Dr. Jason Mills, where he has applied
his foundation in molecular cell biology to study Barrett’s esophagus and upper gastrointestinal (GI) metaplasias
through development of genetic mouse models and establishment of human patient-derived organoids. From a
GI developmental perspective, Barrett’s metaplasia re¿ects a “caudalization” process with loss of esophageal
and gain in both gastric and intestinal traits. Speci¿cally, two pioneering transcription factors involved in GI tract
patterning, SOX2 and CDX2, are likely to involved, and the proposed research is based on the hypothesis that
SOX2 decrease and CDX2 gain are critical steps during BE development and maintenance. To address this
hypothesis, Dr. Jin proposes to carry out two speci¿c aims: 1) Characterize the e¿ects of SOX2 and CDX2 dis-
ruption on foregut homeostasis with and without bile acid treatment, and 2) Determine the e¿ects of SOX2 and
CDX2 restoration on BE maintenance and the molecular heterogeneity of BE.
Continued mentorship and protected research time provided by this grant will ensure the support needed
to complete these aims and allow Dr. Jin su¿cient time to establish an independent research program. Specif-
ically, the current award would provide an important opportunity to train in multi-omics techniques and bioinfor-
matic analyses, while expanding a unique set of tools including genetically modi¿ed mouse models and human
BE and gastroesophageal cancer organoids. Dr. Jin’s career development will be nurtured through continued
mentorship by Dr. Jason Mills and his mentorship committee. Drs. Cristian Ciorfa and Bing Zhang are both es-
tablished computational scientists specializing in bioinformatic integration of multi-omic data; Dr. Kunal Rai is an
expert in epigenomic regulation of development and oncogenesis; and Dr. Sarah Blutt is a leader in advanced GI
organoid culturing techniques. Dr. Jin’s career development will be supplemented by continued growth in grant-
manship, mentorship, leadership, and research community integration through courses and programs o¿ered
at BCM; involvement in ad hoc publication, abstract, and grant reviews; active participation in local and national
research meetings; and preparation of manuscripts and grants. The guidance provided by his highly experienced
research mentor and mentorship committee, the knowledge and technical skills derived from the proposed ex-
periments, and the completion of the carefully outlined career development plan will allow Dr. Jin to successfully
establish an independent research program that will be highly competitive for R01 funding.