Research Spotlight: Nicholas Tolman, PhD

Nicholas Tolman, PhD, first joined the Simon John lab at The Jackson Laboratory in 2013 as a Research Assistant. After deciding to pursue a PhD, he remained in the John lab throughout his graduate studies and continued his work within the group when it relocated to Columbia in 2019. He earned his PhD in Mammalian Genetics from Tufts University in 2023 and now serves as a Postdoctoral Research Scientist in the lab.

Dr. Tolman recently secured his first research grant: the 2026 Knights Templar Eye Foundation Career-Starter Grant, on the topic of Preventing Childhood Glaucoma. Since 1998, KTEF has awarded this highly competitive grant to fewer than 150 institutions nationwide. As one of only 21 recipients of this competitive award in 2026, Dr. Tolman reflects on his journey in science and this significant milestone in his research career.

Tell us about yourself. How did your interest and career in ophthalmology begin?

I first became involved in research as an undergraduate at Connecticut College, where I worked in Dr. Joseph Schroeder’s laboratory studying the biology of memory and addiction. That experience introduced me to the excitement of discovery and sparked my passion for scientific research.

After college, I decided to pursue a PhD and became fascinated by glaucoma through the work of Dr. Simon John and his lab. The eye is also uniquely accessible, allowing direct measurement of disease-relevant phenotypes and efficient testing of treatments in model systems. Most importantly, vision is one of our most important senses. I am motivated by the opportunity to prevent blindness and preserve quality of life. That motivation is especially strong for childhood glaucoma, where vision loss occurs early and carries lifelong consequences.

Are there any mentors who inspired and guided your journey?

My primary mentor throughout much of my scientific journey has been Dr. Simon John. He is deeply invested in trainee success, with many former lab members going on to establish independent research careers. He is an engaged and supportive mentor who provides guidance in science, communication, and career development. As I matured as a scientist, Dr. John gave me the guidance, independence, and resources needed to pursue my own questions in trabecular meshwork and mitochondrial biology. Along the way, many others within the lab and among the scientific network that Dr. John introduced me have provided additional mentorship and shaped my thinking, including Drs. Krishnakumar Kizhatil, Daniel Stamer, Revathi Balasubramanian, and Karayat Nair, among others.

What drew your interest to the John lab?

I am currently a Postdoctoral Research Scientist in the John Laboratory. I remained in the lab for my Postdoc because Dr. John is an internationally recognized glaucoma researcher whose discoveries have transformed our understanding of disease mechanisms and advanced therapies toward clinical testing, and because he is an engaged mentorship in all aspects of running a laboratory, while the labs broad expertise skills meant that I can still learn much more after my PhD.

The John Laboratory has provided an exceptional environment because it encourages following the science wherever it leads. My work has evolved from mouse genetics and clinical style ocular evaluation to genomics, physiology, mitochondrial biology and functional assays, electron microscopy, and metabolomics (and more along the way). That freedom to pursue the biology, combined with outstanding mentorship and resources, has allowed a basic mechanistic discovery to grow into a promising therapeutic strategy.

What is the primary focus of your grant Preventing Childhood Glaucoma?

This project seeks to functionally restore trabecular meshwork development as a treatment for childhood glaucoma. Trabecular meshwork cell death and stalled maturation elevate intraocular pressure, driving optic nerve damage and irreversible vision loss in glaucoma.

Using a mouse model of childhood glaucoma, I discovered that developing trabecular meshwork cells exhibit reduced mitochondrial gene expression and mitochondrial structural abnormalities. Treatments that boost mitochondrial function and ATP production provide partial protection with room for significant improvement.

My project will test the hypothesis that oxidative stress is a key driver of disease using a potent antioxidant therapy. This work could identify a new treatment strategy for childhood glaucoma by targeting the underlying disease mechanisms and resetting normal development in patients.

Why did you choose to focus on this topic?

Childhood glaucomas are severe, blinding diseases that often require lifelong treatment. Current intraocular pressure-lowering treatments are impactful but are frequently inadequate. Surgeries carry significant risks, and medications can cause side effects that must be managed for life. The disease can also cause pain and places a substantial burden on children and their families. A therapy that restores normal trabecular meshwork development and function could reduce or eliminate the need for chronic treatment. It could also complement existing therapies to delay or prevent disease progression. My work suggests that mitochondrial disturbances and oxidative stress are key drivers of childhood glaucoma, and I will test whether lessening this stress maintains trabecular meshwork function and prevents disease.

How did you develop the idea for this topic?

This project emerged directly from my single-cell transcriptomic studies, which provided the first molecular characterization of developing trabecular meshwork cells at single-cell resolution and defined their developmental trajectories. Building on this work, I found that trabecular meshwork cells from childhood glaucoma model mice exhibit altered mitochondrial gene expression programs, a finding supported by striking mitochondrial structural abnormalities identified by electron microscopy.

These observations led me to test therapies targeting mitochondrial dysfunction, which produced promising initial results. This project advances that work by testing the hypothesis that mitochondrial dysfunction and consequent oxidative stress are primary pathogenic mechanisms and by evaluating a potent antioxidant as a therapeutic strategy.

What were some unique challenges when applying for this grant?

The work is ambitious and required substantial effort to develop both the scientific framework and the preliminary data needed to support it. Current childhood glaucoma treatments focus on lowering intraocular pressure but do not address the underlying cause of disease. My goal is to target the primary disease drivers, with the potential to eliminate or reduce the need for lifelong treatment. One of the biggest challenges was generating sufficient preliminary data and building a compelling case for the hypothesis.

What advice would you give other researchers applying for their first grant?

My main advice is to lean on your mentor and scientific network for help. Dr John and many of my former and current colleagues and collaborators were incredibly generous with their time, providing feedback on this grant and helping refine its ideas. Their insights strengthened the science, expanded my thinking, and ultimately helped shape this proposal into what it became. I look forward to returning that generosity by helping others with their grants in the future.

What are your next steps?

My next steps are to characterize the effects of a potent antioxidant on trabecular meshwork cell mitochondrial health, function, and ATP production. I will also determine whether antioxidant treatment can rescue elevated intraocular pressure and attenuate glaucoma in a mouse model of childhood glaucoma. These studies will guide future directions, including testing combination therapies that target multiple aspects of mitochondrial dysfunction. The resulting data will support a Knight Templar Eye Foundation grant renewal, form the basis of a manuscript, and strengthen a future NIH K99/R00 Pathway to Independence Award application.

Are there any scientists whose work inspire you further/you would like to collaborate with?

There are many scientists pushing the boundaries of their fields with whom I would be honored to collaborate. Ultimately, the best collaborations arise from a shared scientific question. One collaboration I am particularly excited to continue is with Dr. Louis Pasquale, a world-class clinician-scientist at Mount Sinai. We previously collaborated on a study from the Pasquale laboratory that showed elevated plasma levels of metabolites that support mitochondrial metabolism and bioenergetic function are associated with reduced glaucoma risk in individuals at the highest genetic risk. Building on this work, I aim to define the mechanisms driving disease in mouse models and translate those discoveries into targeted therapies for patients. With this in mind, I would also be eager to collaborate with pediatric ophthalmologists including Dr. Steven Kane and Dr. Steven Rosenberg at Columbia Ophthalmology.