Axon Regeneration Research

With the goal of benefiting patients with progressive, irreversible peripheral vision loss within a finite time, we have taken the approach of large data-driven experimental research. We have developed a platform for multi-omics (proteome, lipidome, and metabolome) of axon regeneration in multiple organisms: zebrafish, killifish, frogs, and multiple models of mice and rats. We have performed extensive omics analysis of growth cones using various approaches. For the integration of these datasets, we have made new web-based tools such as gcinsights.herokuapp.com. To gain additional insight from historical form and features research, we utilize computer natural language processing (NLP) and have developed web-based tools such as regenx.herokuapp.com. Our multi-omics of axon regeneration continues using different model systems. We are making progress in performing in additional organisms such as rabbits and pigs, isolated single retinal ganglion cells, fractionated axons, and secretome extrinsic to axons. This is being done in collaboration with 32 laboratories in the US and worldwide. We perform optomotor kinetics, visual cliff, and several electrophysiological such as pattern electroretinogram functional analysis. We perform noninvasive optical coherence tomography imaging to determine axon regeneration and reinnervation. Axon membrane extension requires massive lipid rearrangement changes and lipidome enrichment. We study these systems using isolated retinal ganglion cells. We have a dedicated orbitrap mass spectrometer and Stellaris 5 confocal microscope in our laboratory for these studies.

Intraocular pressure homeostasis

Intraocular pressure (IOP) is the most significant risk factor for glaucoma, which leads to irreversible peripheral blindness. Starting with “Irin” in 1955, which became the greatest drug from the eicosanoid lipid class, thus far, there are a number of IOP-lowering drugs, but none that confer IOP homeostasis for even a week. Our comprehensive analysis of lipids and mechanosensitive channels has identified several lipids. Using the lowering of the elastic modulus by lipids or metabolites and significant alteration in trabecular meshwork cell dynamics, we have embarked on understanding how to achieve IOP homeostasis. Several approaches are being experimentally researched to confer IOP homeostasis and their short- and long-term effects on trabecular meshwork cells and anterior eye segment filter structure. 

Changes in brain visual and non-visual areas due to vision deprivation

We are keen on understanding how visual areas are utilized in congenital blindness and in early blinds. Using learned vocalization as a functional trait in zebra finches (Taeniopygia guttata), we are investigating primary ocular pathways, including optic tectum and other brain areas. Our endpoint studies are designed to investigate molecular omics. We find epigenetic changes accompanying long-lasting proteome changes in prolonged visual deprivation consistent with the utilization of visual areas for non-visual function tasks.

Axon regeneration applicable to non-ocular neurodegenerative diseases

Our investigation of extensive available data has revealed reduced axon regeneration and growth cone markers in Alzheimer's brain compared to controls. We are using different approaches to promote growth cone formation and behavioral studies in Alzheimer's mice models that suggest axon regeneration benefits cognitive function. We also have found that common metabolites promote peripheral nervous system axon growth that is recorded for central nervous system axon regeneration. 

Our laboratory houses an online forum open to even high school students. Our laboratory is supported by a local outside research support group  (www.mmrsg.org). We have a strong collaborative and mentoring environment that supports undergraduate, medical, graduate, and postgraduate students. We have successful NIH K08 grant awardees. Past students from the laboratory include successful faculty members, vice chairs of research and industry leaders.