# Dissecting the Human Diabetic Bone Marrow Niche

> **NIH NIH K08** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $163,058

## Abstract

PROJECT ABSTRACT
 Approximately one-third of all diabetic patients develop a diabetic foot ulcer (DFU), of which 50% will result in a
lower extremity amputation due to infection. The medical cost, utilization of emergency care, medical disability, and
increased mortality due to DFUs is disproportionately higher in disadvantaged communities. Current treatment for
DFUs is only 50% effective at preventing amputation because we lack fundamental knowledge regarding the
mechanisms driving the failure of DFUs to heal.
 Type 2 diabetes (T2D) is associated with impaired innate immunity function during wound healing. The innate
immune system is primarily derived from bone marrow hematopoietic stem cells (HSCs). To study the effect of T2D
on the development of human innate immunity, I have developed a novel method to harvest and expand human
HSCs and mesenchymal progenitor cells (MSCs) directly from bone marrow tissue explants collected from T2D and
non-T2D donors that underwent lower extremity amputation. The tissue explant culture recapitulates the bone
marrow niche through the co-culture and expansion of human MSCs and HSCs. My preliminary data demonstrates
that an adipocyte-rich bone marrow microenvironment comprises a specialized niche for a previously unrecognized
HSC population and suggests that bone marrow adipocytes may influence the functional properties of the human
innate immune system development through the leptin signaling pathway.
 The proposed work will define the effect of T2D on bone marrow-derived innate immunity development (Aim 1
and 2). These studies will be complemented by investigating the role of leptin, an inflammatory cytokine produced
by adipocytes, in the dysregulation of normal immune cell development (Aim 3).
 This work will be performed under the continual mentorship of Dr. Silvia Corvera, an expert in adipose tissue
signaling and metabolic disease. I will further build upon relationships with my co-mentors, Dr. Louis Messina, Dr.
Michael Brehm, Dr. Jennifer Wang, and Dr. Katherine Fitzgerald, who are renowned for their knowledge and
expertise in HSCs, humanized immune mouse models, innate immunity in diabetes, and immunology respectively.
This work will be conducted at University of Massachusetts Chan School of Medicine. The results of the proposed
work will provide fundamental understanding of the human diabetic innate immune system and have the potential
to translate these findings into development of in vivo pre-clinical models for DFUs and novel immunotherapies (or
other targeted treatments) to treat non-healing DFUs. If funded, this award will allow me to complete a rigorous
training plan to expand my research across disciplines, learn new techniques, and acquire knowledge and skills to
establish an independent laboratory focused on targeting the diabetic immune system to enhance wound healing,
thereby ultimately preventing lower extremity amputations.

## Key facts

- **NIH application ID:** 10884231
- **Project number:** 5K08DK134952-03
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Tammy Tran Nguyen
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $163,058
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884231

## Citation

> US National Institutes of Health, RePORTER application 10884231, Dissecting the Human Diabetic Bone Marrow Niche (5K08DK134952-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10884231. Licensed CC0.

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