Professor, Department of Ophthalmology
Professor, Department of Pathology
SUMMARY
We are interested in understanding how the extracellular matrix (ECM) regulates cellular functions and tissue homeostasis. The ECM is a network of collagens, proteoglycans, and glycoproteins that facilitates cell communication and function in multicellular organisms. The macromolecular composition and the structure of the ECM change with the needs of the particular tissue. Importantly, in an ECM that is remodeling, the components are more readily available to interact with cells to provide instructive signals during repair and regeneration. We strive to understand dysregulations in these cell-ECM interactions that form the basis of many pathological conditions. Our work on lumican and other members of the small leucine-rich repeat proteoglycans of the ECM show that in addition to regulating collagen fibril assembly, the proteoglycans interact with immune cells to regulate chemotaxis, phagocytosis, and toll-like receptor mediated innate immune responses in a remodeling ECM. Our ongoing work uses mouse models to elucidate the role of ECM proteoglycans in neutrophil, macrophage and dendritic cell functions in bacterial and viral infections.
A second research area in our laboratory focuses on the ECM changes and the underlying genetic causes in a corneal disease called keratoconus where there is a gradual loss in corneal cells and ECM. With progressive loss of vision and a poorly understood etiology, keratoconus is the second most common cause for corneal transplants worldwide. We are sequencing keratoconus patient DNA to identify causal genetic variants, and use cell culture and cornea organoid culture models for functional characterizations of these novel genetic variants.
Current lab members
Masters Student
Mahitha Sattiraju, BS
Research Associate Scientist
George Maiti, PhD
Postdoctoral Fellows
Sean Ashworth, PhD
Madhuri Koduri, PhD
Research Technician
Elizabeth Shin, BS
Past members
Nan Hu, MS
Mackenzie Charter, MS
Tansol Choi, MS
Maithe Rocha Monteiro, de Barros PhD
James Foster, PhD
Jihane Frikeche, PhD
Interim Vice Chair, Research Department of Ophthalmology
Case Western Reserve University, Genetics
Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2021 Jul 06; 118(27):
The ocular surface. 2025 Jan; 35:68-80
Science translational medicine. 2024 Dec 18; 16(778):eado4856
International journal of molecular sciences. 2023 Oct 08; 24(19):
PNAS nexus. 2022 Nov; 1(5):pgac246
Annual review of genomics & human genetics. 2022 Aug 31; 23:193-222
Experimental eye research. 2022 Apr 03; 219:109062