# Defining the Roles of Bone Marrow Adipocytes and FABP4/5 Signaling in Multiple Myeloma Drug Resistance - Diversity Supplement

> **NIH NIH R37** · MAINEHEALTH · 2024 · $79,077

## Abstract

ABSTRACT
The overall goal of this Supplemental research project is to support the career development of Michelle Karam,
who is a post-baccalaureate research assistant in the Reagan lab planning to go to graduate school in
biomedical science. Multiple myeloma (MM) is an incurable blood cancer that results from mutations that
accumulate in the plasma cell. Myeloma cells grow in the rich soil of the bone marrow (BM), first very slowly,
and then more quickly and aggressively, causing degradation of the bone and development of drug resistant
clones. Although therapies exist, novel approaches to myeloma therapy are needed. Our prior work suggested
that myeloma cells can become drug resistant and proliferate faster through support from proteins called fatty
acid-binding proteins 4 and 5 (FABP4 and FABP5). In Specific Aim 1 of our R37 parent award, we are
analyzing how BM adipocytes contribute to myeloma by using novel, three-dimensional (3D), tissue
engineered cancer models. In Specific Aim 2, we use mouse models to study the roles of the FABP members
in MM, as well as the roles of BM adipocytes. The long-term goal of our work is to understand molecules and
mechanisms driving MM growth; this Supplement and Parent project specifically will identify new mediators
driving MM and propose paradigm-shifting concepts to guide the development of new anti-MM therapies.
The proposed studies in this Supplement will not overlap with ongoing work on the Parent award, but will
complement and add translational significance to the findings. We have submitted a Method to Extend
Research in Time (MERIT) Award Extension Request that would extend the R37 grant for two years through
June 2027. This is a two year supplement request with Aim 1 in year one and Aim 2 in year two, if the
extension is granted. Both Supplement Aims will be used to identify translationally significant effects and
mechanisms of FABP inhibitor action on tumor cells and on the tumor immune microenvironment. Our
Supplement Specific Aim 1 is to Test the feasibility for orally-administered FABP inhibitors to slow tumor
progression and increase mouse survival in an immunocompetent in vivo MM model. This will be used
to develop drug delivery doses and oral gavage methods for effectively inhibiting MM growth, which we will use
for the following Aim. Supplement Specific Aim 2 is to: Examine mechanisms of action of FABP inhibitors
in the MM BM environment, including effects on tumor and surrounding tumor microenvironment cells.
This Aim will use novel methodologies and data analyses methods for flow cytometric and spatial
transcriptomic analysis of MM cell growth in the BM of mice, and the effects of FABP inhibitors on the tumor
and non-tumor microenvironment cells. This work should thus illuminate the actions of FABP inhibition not only
on tumor cells, but also on surrounding cells, which will be essential for moving towards the clinic and
thoroughly understanding the potential roles of the FABPs in MM patie...

## Key facts

- **NIH application ID:** 11063569
- **Project number:** 3R37CA245330-05S1
- **Recipient organization:** MAINEHEALTH
- **Principal Investigator:** Michaela R. Reagan
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $79,077
- **Award type:** 3
- **Project period:** 2020-07-01 → 2025-03-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11063569

## Citation

> US National Institutes of Health, RePORTER application 11063569, Defining the Roles of Bone Marrow Adipocytes and FABP4/5 Signaling in Multiple Myeloma Drug Resistance - Diversity Supplement (3R37CA245330-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11063569. Licensed CC0.

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