# Investigating the Microenvironmental Dysregulation and Polypharmacy Impact during Acute Myeloid Leukemia in an in vitro model of the human bone marrow and in vivo models.

> **NIH NIH F99** · UNIVERSITY OF ROCHESTER · 2024 · $39,957

## Abstract

Project Summary and Abstract
This award will support Azmeer Sharipol, M.S., long-term goal of developing the expertise and skills needed to
become an independent investigator exploring the role of polypharmacy and microenvironmental dysregulation
in acute myeloid leukemia (AML) using an applied microphysiological systems (MPS) approach. The standard
daunorubicin and cytarabine (DNR) chemotherapy for AML result in a 5-year survival rate of less than 30%.
70% of patients >60 years old succumb to the disease after 1-year of diagnosis. Polypharmacy, which is the
use of ³5 drugs to treat comorbidities, is common in vulnerable patients. However, it remains unclear whether
polypharmacy has an impact on AML chemotherapy. AML studies mostly focused on finding the intrinsic
mutations within the hematopoietic stem cell lineage that give rise to dysfunctional AML cells. However, the
role of the bone marrow microenvironment (BMME) is often overlooked. Studies using in vivo models showed
that AML cells can dysregulate the BMME through cell-cell interaction and chemokine signaling. Azmeer’s
sponsor, Dr Benjamin Frisch, showed that AML cells inhibit osteoblastic cell function via C-C motif chemokine
ligand 3 (CCL3) in a clinically relevant murine AML model. However, it is challenging to prove the AML-BMME
signaling in human cases due to the lack of reliable in vitro model of the human BMME. Azmeer Sharipol will
address these gaps in research through an innovative research plan that leverages his background in applied
MPS. For the F99 phase, Azmeer will develop an in vitro human BMME-chip model using Emulate Chip-S1™
microfluidics systems and fibrin-hydrogel encapsulation containing osteoblastic, endothelial, and stromal cells
compartments that are important regulator of stem cell maintenance and differentiation. Using the BMME-chip,
he will elucidate the role of CCL3 in the dysregulation of the human BMME and investigate the targeting of
CCL3 receptors, CCR1 and CCR5, using small molecule inhibitors to rescue BMME dysregulation in AML-
BMME-chip. For the K00 phase, Azmeer will explore the effects of polypharmacy from common comorbidity
drugs including metformin and captopril in addition to standard chemotherapies on the BMME function using
the AML-BMME-chip, and in vivo models of AML. Azmeer Sharipol has worked closely with his sponsors to
develop a training plan that emphasized on building new knowledge and methodological skills to prepare him a
smooth transition into an independent research career path. The training plan includes improving knowledge in
cancer biology, cancer cell signaling, clinical pharmacology, and bioinformatics analysis. Azmeer and his
mentors also developed a plan for identifying a postdoctoral mentor. Together, the proposed research and
training plan provide optimal opportunities and structure for Azmeer to develop new skills and progress toward
cancer researcher.

## Key facts

- **NIH application ID:** 10987768
- **Project number:** 1F99CA294129-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Azmeer Sharipol
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $39,957
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987768

## Citation

> US National Institutes of Health, RePORTER application 10987768, Investigating the Microenvironmental Dysregulation and Polypharmacy Impact during Acute Myeloid Leukemia in an in vitro model of the human bone marrow and in vivo models. (1F99CA294129-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10987768. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*