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Neoglycosylation Epitopes in Metaplasia and Cancer

Award Number: K08DK132496
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Neoglycosylation Epitopes in Metaplasia and Cancer - PROJECT SUMMARY / ABSTRACT This application proposes a five-year research career development program focused on determining how glycosylation epitopes expressed during metaplasia and cancer contribute to these clinically significant cellular transformations. The applicant, Jeffrey W. Brown, M.D., Ph.D., is an Instructor of Medicine in the Division of Gastroenterology at Washington University School of Medicine. Since completing gastroenterology fellowship, Dr. Brown had worked in the laboratory of Jason Mills, where he has discovered a novel cellular process that he calls cathartocytosis [Greek: cellular cleansing] which is used by cells to efficiently dedifferentiate in the processes of metaplasia and cancer. He has subsequently determined that cathartocytosis is annotated by the glycan 3’-Sulfo-LeA/C and mice null for galectins that preferentially bind this epitope either fail to perform cathartocytosis or fail to package sulfomucins into mature granules. As glycobiology is a new field for Dr. Brown, Stuart Kornfeld will serve as his primary mentor with continued support from Jason Mills (Co-Mentor). Together, the candidate will be uniquely positioned to acquire the knowledge and skill set necessary to develop an independent research program investigating how specific glycosylation epitopes modulate tissue transformation and differentiation states in metaplasia and cancer. The expression and secretion of sulfomucins is uniformly present in Barrett’s esophagus and esophageal cancer, is the defining feature of type III [high-risk] gastric intestinal metaplasia, and is currently the best biomarker for detecting high-grade dysplasia and cancer in pancreatic cystic lesions. Using a comprehensive approach involving cell lines, organoid culture, and murine models, the experiments proposed herein will determine the proteome carrying 3’-Sulfo-LeA/C, the cellular signaling and transcriptional profile regulating its synthesis and secretion, as well as the molecular mechanism by which specific galectins modulate cellular differentiation. Ultimately, with the mentorship provided by Stuart Kornfeld, Jason Mills, and the research advisory committee, the knowledge and technical skills derived from the proposed experiments, and completion of the outlined career development plan, Dr. Brown will be well-prepared to establish an independent research program and is expected to be highly-competitive for R01 funding.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $165,062 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	2/18/2025	NON-COMPETING CONTINUATION	$165,062
														Subtotal = $165,062

Issue Date FY: 2024 ( Subtotal = $165,062 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/26/2024	NON-COMPETING CONTINUATION	$165,062
														Subtotal = $165,062

Issue Date FY: 2023 ( Subtotal = $165,062 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/20/2023	NON-COMPETING CONTINUATION	$165,062
														Subtotal = $165,062

Issue Date FY: 2022 ( Subtotal = $166,562 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/25/2022	NEW	$166,562
														Subtotal = $166,562

Grand Total All Awards = $661,748

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Neoglycosylation Epitopes in Metaplasia and Cancer

Award Number: K08DK132496

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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