# Decoding endocrine and paracrine communication through mammokines

> **NIH NIH DP1** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $800,000

## Abstract

Project Summary
Interactions among different organs are pivotal in developing pathological conditions like obesity and type 2
diabetes. Substantial research efforts have been directed towards comprehending how communication between
cell types such as adipocytes, hepatocytes, and islets contribute to and respond to specific disruptions
associated with metabolic diseases. There remains an essential yet relatively unexplored question: how does
the secretome of the mammary gland's luminal epithelium influence inter-organ communication in the context of
obesity? Breastfeeding holds a significant role in promoting the health of mothers and reducing the risk of
diabetes, benefiting both maternal and neonatal health. It also protects against cardiovascular diseases, obesity,
and other metabolic disorders for both the mother and child. However, obesity can disrupt mammary gland
function and development, potentially affecting maternal well-being and the health of offspring. Recent
technological advancements, such as single-cell transcriptomics and precision proteomics, have opened up
opportunities for unbiased exploration and the discovery of signaling molecules involved in inter-organ
communication. We recently employed a bioinformatics framework based on single-cell transcriptomic
correlations, integrating data from multiple datasets with publicly available resources to identify secretory factors
from mammary duct luminal cells that influence surrounding adipocyte metabolism. We refer to these factors as
"mammokines." Our innovative research endeavor seeks to combine transcriptomics and proteomics to unveil
the ambiguities surrounding the mammary gland's function as an endocrine organ and the impact of obesity on
its action. The primary goal of this project is to discover new mammokines that may have vital roles in paracrine
and endocrine signaling, influencing the function and homeostasis of the liver, pancreas, adipose tissue, and the
mammary gland itself, potentially affecting the progression of obesity and Type 2 diabetes phenotypes. These
mammokines could serve as valuable biomarkers for obesity and diabetes in women. We also aim to determine
which pathways are conserved from mice to humans and investigate the physiological consequences of
disrupted endocrine communication through functional experiments. The success of these objectives relies on
integrating transcriptomics, proteomics, computational, and experimental approaches, which is supported by the
extensive training and expertise of the Principal Investigator and collaborators. We believe this research has
great potential to advance our understanding of women's metabolic health and inspire innovative strategies for
obesity and diabetes therapy.

## Key facts

- **NIH application ID:** 10937401
- **Project number:** 1DP1DK140003-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Prashant Rajbhandari
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $800,000
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937401

## Citation

> US National Institutes of Health, RePORTER application 10937401, Decoding endocrine and paracrine communication through mammokines (1DP1DK140003-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10937401. Licensed CC0.

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