John Lab

Our research investigates glaucoma as well as other eye and neural diseases. Glaucoma is a common neurodegenerative disease that leads to the death of neural cells. Additionally, we collaborate to develop and test miniature devices to enhance research and monitor/treat disease. Major goals are to provide new understanding of disease mechanisms and new devices, all to improve the care and treatment of patients. Our laboratories are located at the Department of Ophthalmology at Columbia University Irving Medical Center as well as at the Zuckerman Mind Brain Behavior Institute.

Many of our studies focus on glaucoma, one of the most common neurodegenerative diseases. Glaucoma is a major cause of blindness and is often associated with elevated pressure within the eye itself, called intraocular pressure (IOP). This harmful pressure damages retinal ganglion cells (RGCs) resulting in a pressure-induced neurodegeneration. The molecular processes that raise IOP and damage retinal ganglion cells are only partially understood.

We study the genetics and genomics of glaucoma with established international collaborators and with ophthalmologists. To complement these studies with a powerful experimental system, we use mouse models. Combining genetics with genomics, cell/molecular biology and physiology to understand glaucoma, we are identifying new genes, pathways and aberrant processes that lead to high IOP and glaucoma. We are determining how high IOP damages retinal neurons as well developing resilience-boosting and neuroprotective treatments to shield RGCs from glaucoma. Resilience-boosting treatments adjust cellular metabolism and/or increase other cellular resources that protect from stress, enhancing the ability of ocular tissues to fend off disease.

We demonstrated that vitamin B3 (nicotinamide) potently prevents glaucoma in a mouse model. We have a growing interest in the role of altered metabolism in various neurodegenerations and in IOP elevation and retinal disease. We are involved with clinical trials and other studies to further evaluate the efficacy of vitamin B3 and the role of metabolism in human glaucoma.

Training is also an important component of our program. with trainees obtaining hands on experience while conducting research projects. Our approach is multidisciplinary with projects involving diverse expertise including clinical evaluation, genetics, genomics/gene expression (single cell sequencing, spatial transcriptomics, etc.), gene therapy, molecular biology, pathology, physiology, neurobiology, microscopy, imaging and metabolomics/metabolism. We are generating large complex datasets that require data science/biostatistics and innovative computational analyses. This provides a fertile training environment with laboratory members progressing to top graduate and medical programs. After completing their training, almost all of our postdoctoral trainees have obtained faculty positions with the others obtaining appropriate high-level scientific positions of their choice. We are always interested in considering dedicated, high-caliber candidates at various career stages.