Shukti Chakravarti, PhD

SUMMARY

The extracellular matrix (ECM), composed of collagens, glycoproteins, and proteoglycans, is a complex and dynamic structure that is specialized for each tissue type and cellular niche. My research focuses on ECM-cell interactions that drive inflammation, infection, and tissue repair. A significant focus in our laboratory is the cornea, an ECM-rich tissue that serves as both a protective barrier and a refractive structure of the eye. We discovered that the proteoglycan lumican plays a crucial role in regulating collagen fibril assembly. In lumican-deficient mice, collagen fibrils are disorganized across various ECM tissues. In the cornea, this results in excessive light backscatter, leading to corneal clouding, while in tendon, skin, and cartilage, it contributes to biomechanical weakening.

Beyond its structural role, we identified another key function of lumican. In remodeling ECM, lumican and other related proteoglycans interact with immune cells, including neutrophils, macrophages, and dendritic cells, to regulate innate inflammatory signaling. Surprisingly, these proteoglycans are internalized by immune cells where they regulate vesicular trafficking of receptors and ligands for additional control of inflammatory responses. These findings prompted us to explore how the unique ECM within lymphoid organs influences immune cell behavior. Currently, we are investigating ECM composition and immune cell phenotypes in lymph nodes using mouse viral infection models.

In parallel, our work on stem cell-derived ocular organoids provides a versatile and ethical platform for modeling human diseases. We use these organoids to study ECM-cell responses to infection in a controlled in vitro environment, and co-culture with specific immune cell types to mimic immune cell infiltration in infections.

Another major area of research in my laboratory is keratoconus, a corneal disease with ECM degeneration and scarring that lead to vision loss. We use proteomic, transcriptomic and genomic approaches on patients to identify genetic variants and disease mechanisms underlying keratoconus. The cornea organoids we developed are being used for functional tests of specific genetic variants and pathways.

Current lab members

Research Associate Scientist

George Maiti, PhD 

Postdoctoral Fellows

Sean Ashworth, PhD

Madhuri Koduri, PhD

Interns

Trisha Sinha

Past members

Elizabeth Shin

Nan Hu, MS

Mackenzie Charter, MS

Tansol Choi, MS

Maithe Rocha Monteiro, de Barros  PhD 

James Foster, PhD

Jihane Frikeche, PhD