Research

Erythrocytes are major regulators of metabolism (function) and are produced by erythropoiesis (development) in the bone marrow. We found that these processes control cellular and tissue oxygen levels and are critical for proper musculoskeletal tissue regeneration. However, the impact of erythrocytes and erythropoiesis on cartilage restoration and bone regeneration has yet to be studied.

Our aim is to understand erythrocyte function & development...

to regenerate bone

The immediate interruption of the bone marrow microenvironment during long bone trauma activates local erythropoiesis. Erythroid progenitors have been described to direct iron and oxygen metabolism. We study how erythroid progenitors direct the local metabolic and immune microenvironment instructing regeneration during fracture repair.

to restore cartilage

Cartilage is avascular and requires a hypoxic niche to maintain proper metabolism and matrix integrity. Oxygen diffuses from the synovial fluid into the cartilage matrix. We elucidate dynamic intra- and extracellular oxygen signatures in cartilage, synovial fluid, and synovial membrane in vivo during post-traumatic OA and hemarthrosis.

to advance biomaterials

We leverage fundamental knowledge to develop novel, programmable biomaterials by engineering microenvironmental cues to guide erythroid stem cell fate and by targeting cellular oxygen to re-establish the hypoxic cartilage niche for tissue restoration.

Key Methods & Collaboration Partners

Oxygen monitoring

We have developed methods to measure & regulate oxygen levels in skeletal tissue.

Collaboration partners:

Cameron Koch, PhD (UPenn)

Sergei Vinogradov, PhD (UPenn)

Jay Patel, PhD (Emory)

Single-cell analysis

We specialize in studying single cells comprehensively through flow cytometry & sequencing.

Collaboration partners:

Joel D. Boerckel, PhD (UPenn)

Vikram Sunkara, PhD & Mir-Farzin Mashreghi, PhD (DRFZ Berlin)

Preclinical models

We use a variety of advanced in vitro and in vivo models to promote clinical translation.

Collaboration partners:

Manuela Raimondi, PhD (Polimi, Milan)

Kate Schmidt-Bleek, PhD (Charité Berlin)

Paulin Jirkof, PhD (UZH, Zurich)

Bone analysis & NanoCT

Our expertise in bone parameter analysis helps us uncover how erythroid and bone cells communicate.

Supported by:

Michigan Integrative Musculoskeletal Health Core Center

Histology

We use sophisticated histology and multiplex fluorescence microscopy to study tissue changes and cell phenotypes.

Supported by:

Michigan Integrative Musculoskeletal Health Core Center

Clinical Samples

By integrating clinical sample analysis with our in vitro & in vivo studies, we strengthen the translational impact and clinical relevance of our findings.

Clinicians:

Brandi Hartley, MD (Ortho UMich)

Shikha Sachdeva, MD (Ortho UMich)

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