# BLRD Merit Review Research Career Scientist (RCS) Award (IK6)

> **NIH VA IK6** · VETERANS HEALTH ADMINISTRATION · 2021 · —

## Abstract

The prevalence of obesity and associated co-morbidities, including type 2 diabetes and cardiovascular disease,
has increased dramatically in the past several decades. It is well-established that an immune component
contributes to the etiology of metabolic diseases – especially when driven by obesity. For example, nearly all of
the immune cells in existence have been shown to reside in adipose tissue (AT). Resident macrophages in AT
are thought to contribute to development and proper function of the AT by various homeostatic functions. During
weight gain, the numbers and phenotypes of all of the immune cells in AT change such that the overall milieu
becomes pro-inflammatory, promoting insulin resistance at the tissue and systemic levels. The Hasty laboratory
currently has 2 main areas of investigation in this burgeoning area of immunometabolism:
Immunologic memory to weight loss and weight cycling: While weight loss is the ideal approach to reduce the
negative metabolic consequences of obesity, it is clear that sustained weight loss is difficult to achieve. Bouts of
weight loss followed by subsequent weight-gain lead to “weight-cycling”. Interestingly, several studies in humans
demonstrate that weight-cycling increases the risk of developing metabolic diseases. Dr. Hasty and others have
published data showing antigenic responses in AT during weight gain. Thus, she has developed the hypothesis
that weight-cycling results in a T cell-driven secondary immune response that heightens inflammation in AT,
leading to local and systemic insulin resistance (IR). In addition, she has begun to study whether macrophages
also “remember” the obesogenic environment in a process called trained innate immunity. This work is funded
by her VA Merit Award and by a new Innovation award from the American Heart Association.
Macrophage iron handling: Dr. Hasty’s group discovered a novel population of macrophages in AT that are
critical for control of local iron concentrations, thereby contributing to adipogenesis and to protection from
oxidative stress. Her laboratory’s recent advances offer an excellent opportunity to define a role for resident AT
macrophages in iron-related control of AT homeostasis. The intrinsic immunometabolism, i.e. fuel utilization and
bioenergetics of the cell, and extrinsic immunometabolism, i.e. secreted products that affect the surrounding
tissue environment, are manipulable properties that influence how macrophages contribute to tissue
homeostasis. We will determine how iron cycling influences both arms of the immunometabolic role of AT
macrophages, thereby influencing systemic insulin action. This work is funded by a new R01.
Dr. Hasty has published over 100 peer-reviewed manuscripts in this area in high impact journals including
Diabetes, Nature Medicine, Am. J. Physiol. and Mol. Metab. She has always maintained a strong cohort of young
scientists within her group, and is keen on training the next generation of immunometabolism experts. Dr. ...

## Key facts

- **NIH application ID:** 10221206
- **Project number:** 1IK6BX005649-01
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Alyssa H Hasty
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221206

## Citation

> US National Institutes of Health, RePORTER application 10221206, BLRD Merit Review Research Career Scientist (RCS) Award (IK6) (1IK6BX005649-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10221206. Licensed CC0.

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