# Molecular Mechanisms Regulating and Interpreting BMP Signaling

> **NIH NIH R35** · CORNELL UNIVERSITY · 2021 · $520,142

## Abstract

PROJECT SUMMARY/ABSTRACT
Molecular mechanisms regulating and interpreting BMP signaling
Bone morphogenetic proteins (BMPs) belong to the transforming growth factor  (TGF) superfamily of ligands
and the BMP signaling pathway plays roles in multiple developmental and homeostatic processes. Malfunction
of the pathway causes many somatic and hereditary disorders in humans, including cardiovascular diseases
and cancer. Thus multiple levels of regulation must exist in vivo to ensure proper spatiotemporal specificity,
level, and duration of BMP signaling in the right cellular context. We have developed a novel, highly specific
and sensitive genetic screen in C. elegans that has allowed the identification of multiple new and evolutionarily
conserved modulators of the BMP pathway. These modulators span from extracellular secreted proteins, to
cell surface integral membrane or GPI-anchored proteins, to proteins involved in intracellular trafficking,
highlighting many levels of regulation on BMP signaling. Excitingly, several of these factors have not been
previously implicated in regulating BMP signaling in any systems. In addition to the regulators, we have also
identified a cell type specific target of BMP signaling in the C. elegans postembryonic mesoderm. Determining
how the BMP modulators function in regulating BMP signaling and how BMP signaling is interpreted in specific
cellular contexts are the research focuses under this MIRA. We propose to use a multifaceted approach that
combines molecular genetic, genome editing, biochemical and high- resolution imaging techniques to dissect
the functions of the BMP modulators in C. elegans. At the same time, we are also branching out to determine
the functions of these factors in mammalian tissue culture cells. Our research has been funded by NIGMS
since 2002 when I first set up my lab at Cornell University. Over the years, we have made substantial progress
and have generated a set of tools/reagents that put us in a unique position to carry out our proposed research.
Our experiences and expertise, coupled with the flexibility offered by the MIRA mechanism to pursue new
research opportunities as they arise, will allow us to make sustained progress in our research. Our studies are
bound to provide important insights into the complex and intricate mechanisms regulating and interpreting BMP
signaling at single cell resolution in a multicellular living animal. They may also provide potential therapeutic
targets for the different diseases caused by mutations in the BMP pathway.

## Key facts

- **NIH application ID:** 10089459
- **Project number:** 5R35GM130351-03
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Jun Liu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $520,142
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10089459

## Citation

> US National Institutes of Health, RePORTER application 10089459, Molecular Mechanisms Regulating and Interpreting BMP Signaling (5R35GM130351-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10089459. Licensed CC0.

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