# Mechanistic Understanding for the Role of Lin28b in Pancreatic Cancer Progression

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $127,680

## Abstract

Project Summary
Pancreatic ductal adenocarcinoma (PDA) is a leading cause of cancer-related death in the US, for which
treatment remains basically unchanged in the past three decades. Although patients often die from metastatic
lesions, there are no specific diagnostic markers or therapeutic strategies aimed at treating metastases,
particularly due to an almost complete lack of knowledge on the molecular drivers of metastatic progression.
Using a combination of comparative transcriptomics and a novel functional soft-agar screen, we identified a
new factors, DennD5b (DENN domain containing 5b, a RAB-GEF protein of unknown function), that is
specifically expressed in metastatic lesions and its inhibition completely halted the growth of metastases
without affecting the primary tumors; furthermore, preliminary data indicate that DennD5b modulates lipid
metabolism, providing metabolic fitness to these metastatic cells, all together indicating that these lesions
evolve by acquiring non-genetic adaptations. In this proposal, we will take advantage of biochemistry, cell
biology, metabolomics and genetically-engineered mouse models in order to molecularly characterize this
factor, with the potential to change treatment for this devastating disease.

## Key facts

- **NIH application ID:** 10558954
- **Project number:** 3R01CA235412-04S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** NABEEL El-BARDEESY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $127,680
- **Award type:** 3
- **Project period:** 2019-02-19 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10558954

## Citation

> US National Institutes of Health, RePORTER application 10558954, Mechanistic Understanding for the Role of Lin28b in Pancreatic Cancer Progression (3R01CA235412-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10558954. Licensed CC0.

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