# NIH grant: Role of Hyaluronan in Modulating Multiscale Biological Responses to Mechanical Stimuli (1R35GM165423-01) — retained record

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NIH grant 1R35GM165423-01: Role of Hyaluronan in Modulating Multiscale Biological Responses to Mechanical Stimuli
Institute: {'code': 'GM', 'abbreviation': 'NIGMS', 'name': 'National Institute of General Medical Sciences', 'admin_org_id': '12500024', 'admin_funding_url': ''}. PI: Deva D Chan. Award: $422191.
Start: 2026-07-10T00:00:00.
PROJECT SUMMARY
Hyaluronan is a simple polysaccharide that is present in almost all tissues of the body. Despite this simplicity,
hyaluronan has diverse physical and biological functions in human health, injury, and disease. Its bioactivity
and signaling pathways are dependent on complex and interacting factors, including the enzyme isoform that
synthesizes it, molecular weight, receptor binding, and protein interactions in forming an hyaluronan-rich
pericellular coat. Hyaluronan also interacts with proteins and proteoglycans to provide structure and
mechanical resilience to the pericellular and extracellular matrix that surrounds cells. The content, distribution,
and other properties of hyaluronan can also be altered by biophysical cues to the cells, including substrate
stiffness and mechanical loading. Because HA production and degradation is inextricably linked to tissue
biomechanics and cell behavior, it is of critical importance to understand the mechanobiology of HA synthesis
and turnover, particularly in progenitor cell populations and tissue types where pericellular HA is fundamental
to cell functions. In this Early Stage Investigator (ESI) Maximizing Investigator Research Award (MIRA)
application, we propose to characterize the HA “mechanics-matrix” feedback loop at multiple length scales
(cell, tissue, organism or systemic). We target biophysical mechanisms for regulating hyaluronan in bone
marrow- and adipose-derived stromal cells due to their roles in tissue maintenance and repair as well as their
utility in tissue engineering and regenerative medicine. We will probe how various biophysical factors in bone
marrow- and adipose-derived stromal cell cultures drive hyaluronan turnover and modulate
mechanotransduction (Project 1) and evaluate the response of heterogeneous cell populations in adipose and
bone marrow to increased systemic mechanical loading through exercise (Project 2). Together, these
proposed research directions focus on the bidirectional interaction between matrix and mechanics, using a
combination of experimental and computational approaches to bridge towards human translation. Because of
the ubiquity and diversity of function of hyaluronan in the mechanically active human body, the results of this
work have broad potential to impact human health and treatment of various mechanobiology and hyaluronan-
linked disorders, including chronic diabetic wounds, lung inflammation and fibrosis, inflammatory bowel
disorders, atherosclerosis, osteoarthritis, and cancer. This work will also use mouse models to support the shift
to non-animal models (or new approach methodologies) by developing mechanobioreactors and evaluating
which features of hyaluronan metabolism and mechanobiology can and cannot be replicated in vitro and in
silico and building the experimental and computational frameworks to enable future work in other hyaluronan-
rich systems. This work supports our laboratory’s long-term goal of achieving deeper understanding of how
biomechanical signals at multiple scales can alter hyaluronan in human health and disease.
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