Research Interests

Cells in our body continually interact with the surrounding environment to obtain nutrients and communicate with their neighbors.

The cells and the extracellular space constitute the environment that determines the tissue function, cell differentiation, and healthiness of the cell. Interestingly, cells shape their extracellular matrix by actively synthesizing and secreting molecules into the extracellular space.

In the retina, the neuronal photoreceptors cells and the glial retina pigment epithelium (RPE) cells interact through a specialized extracellular matrix called Interphotoreceptor Matrix (IPM). Patients with mutations in molecules of the IPM develop blinding diseases.  

Areas of Interest:

Genesis and dynamics of the matrix

The interphotoreceptor matrix is compounded by a mesh of molecules in constant synthesis and degradation. These molecules are required to integrate into the matrix by interacting with other molecules. In addition, the interaction between the matrix and cell membrane proteins allows the cell to sense the matrix environment.

Which are those molecules, how do they interact, and why they are important for the health of the glia and photoreceptors are the questions we try to address in our lab.

Extracellular matrix changes in mutant mice.

Immunohistochemistry analysis of photoreceptor extracellular matrix.

Link to paper.

IPM fluid dynamics

The interphotoreceptor matrix provides the media where nutrients, ions, and molecules traffic from cell to cell. Surprisingly we know very little about the size of the matrix and the flow of molecules and ions through the matrix. What is the true size and shape of the matrix? How do molecules and ions move along the matrix? Can we model the flow of nutrients through the matrix and predict disease mechanisms?     

Cone photoreceptor extracellular matrix.

Retina and RPE metabolic changes in mice with affected interphotoreceptor matrix.

Electron microscopy shows extracellular matrix changes in mutant mice.

Differential equations model the response of photoreceptor to light

 Link to paper. 

Can we improve vision in patients with affected extracellular matrix proteins?

Patients with mutations in the interphotoreceptor matrix proteoglycans IMPG1 and IMPG2 develop retinitis pigmentosa or macular dystrophy vision diseases. We are developing adenovirus-based gene therapy to rescue rapid RP progression in children.

Gene therapy workflow.

Besides helping to cure blinding diseases, we broadly enrich diverse scientific fields such as aging, neurodegeneration, biomaterials, brain-machine interface, 3D tissue culture, and computational neuroscience.

Publications