Congratulations to Dr. Winston Lee for his awarded K99 Grant!

Winston Lee, PhD, a postdoc in Dr. Rando Allikmets’ lab, was recently awarded his K99 grant: Structured quantification of inherited macular disease phenotypes as the basis for automated algorithms to determine causal genes. We spoke with Dr. Lee to learn what inspired him, from his scientific beginnings to his most recent achievement.

• Tell us about yourself. What motivated you to become a scientist?

I never envisioned myself as a scientist. If I had to pinpoint a defining moment, it would be the first time I saw an adaptive optics image of the retina. That experience unlocked my fascination with retinal imaging, particularly the idea that a single “photograph” from a patient could contain vast amounts of biological information, waiting to be decoded through advanced image analysis.

Beyond that, I was captivated by the deeper complexity of how these disease features were ultimately encoded in the genome. This intersection between clinical phenotypes and genetics drew me in and set me on my path. Yet, for much of my journey, I never felt like I was "doing science" in the traditional sense—it felt more process of cumulative discovery that unfolded over time.

• Are there particular mentors who inspired and guided your journey?

Over nearly 15 years in the department, I have had the privilege of learning from and being shaped by dozens of distinguished faculty members. However, a few mentors had a particularly profound impact on who I am today. Prof. Stephen Tsang, M.D., Ph.D., brought me into this field and opened my eyes to clinical retina, teaching me virtually everything I know about recognizing and interpreting disease manifestations in patients. Prof. Janet Sparrow, Ph.D., introduced and deepened my understanding of retinal imaging, guiding me through the technical sophistication of quantitative autofluorescence. Prof. Rando Allikmets,Ph.D., who was my primary mentor for over a decade, ignited my passion for human genetics which now forms the bedrock of my own research area. Lastly, Prof. Stanley Chang, M.D., through his quiet encouragement, gave me the confidence to pursue a life in academia,

Beyond the work itself, the time I spent with them gave me a broader perspective on what it means to be a scientist. I learned the importance of pursuing questions relentlessly, trusting my scientific intuition, and maintaining resilience during tough times. But perhaps most importantly, they showed me how to wake up each day with a genuine love for the work we do.

• Tell us about your doctoral studies

I chose to study genetics because, of all the disciplines I had encountered, it was the most challenging to intuit. Unlike biomedical imaging, where pathology can be observed directly, genetics operates at a molecular level making it essentially “invisible” to the senses.

In 2018, I entered the Ph.D. program in Genetics & Development as part of the Coordinated Doctoral Programs in Biomedical Sciences. I joined the lab of Vincenzo A. Gennarino, Ph.D., who was rapidly gaining recognition for his work on neurodevelopmental disorders. Over the next four years, my dissertation work led to the discovery of a novel neurodevelopmental syndrome caused by de novo “short-circuiting” mutations in the CERT1 gene and the identification of incompletely penetrant hypomorphic mutations in the PUM1 gene, which underlie to a rare form of spinocerebellar ataxia.

• What drew you to pursue your postdoc in the Allikmets lab?

I chose to return to Dr. Allikmets’ lab for my postdoctoral work for several reasons. While it may seem like a step back into familiar territory, the field of medical genetics is evolving rapidly. The tools and knowledge available today are vastly different from those that existed prior to my doctoral training.

Additionally, the Allikmets lab houses one of the largest databases of inherited retinal dystrophy patients—arguably the largest maintained by a single research group. In human genetics, access to large and well-characterized patient cohorts is invaluable. This unique resource made the lab an ideal place to further my own research as an independent investigator.

• What is the primary focus of your project/grant?

The focus of my K99/R00 grant is to leverage the detailed phenotypic landscape of patients with inherited macular dystrophies to uncover critical genomic insights.  To accomplish this, I will assemble a large patient cohort in collaboration with clinical colleagues within the department and outside, perform targeted set of imaging tests to characterize the full range of retinal features in each patient, sequence their genomes to identify underlying causal genes and analyze patterns that distinguish different molecular etiologies.

• Why did you choose to focus on this topic? How did you develop the idea for it?

Although my doctoral training provided insights into the microscopic world of genetics at the cellular level, what truly fascinated me was the bidirectional relationship between patient-level disease manifestations and the genomic landscape.

One of the fundamental challenges in genetics is that deep phenotypic insights are rarely leveraged, largely because geneticists often have limited expertise in clinical medicine, and vice versa. By integrating detailed patient phenotyping with genomic analysis, my grant project can bridge this gap and can unlock new areas of genetic discovery. My unique background, spanning both fields, positions me to help bridge this gap and drive this paradigm shift forward.

• What were some unique challenges when applying for this grant?

One of the most valuable skills gained during a Ph.D. is the ability to write and prepare scientific manuscripts. By the time I finished my dissertation, I had refined this skill considerably. However, I quickly realized that grant writing is an entirely different challenge.  In addition to technical proficiency, successful grant writing demands an extra layer of persuasion and strategic storytelling—a skill set often not essential for academic articles. Transitioning into this style was one of the biggest hurdles I faced.

Writing the K99 grant as the principal investigator also required me to consider aspects beyond the scientific project itself—such as budget planning, personnel salaries, facility requirements, and administrative logistics. This experience illuminated the stark difference between “doing science” and “making science possible”.

• And finally, what advice would you give other aspiring young scientists?

My advice to young aspiring scientists is to physically immerse yourself in the broader landscape in which your work exists. For instance, if you’re a biochemist solving the structure of a protein that can be used to treat congenital heart disease, find a cardiologist who can mentor you on the side to understand how this particular condition is diagnosed in patients. For those considering a shift in direction, exploring related disciplines can provide new experiences that may better align with evolving interests. For those committed to an academic career in their current field, interdisciplinary exposure offers valuable tools and a broader perspective, enabling the formulation of more holistic research questions that may be overlooked by those with a narrower focus. Staying within the broader landscape of your expertise—rather than making a complete departure—allows you to build on your prior experience and leverage established professional networks, which are often critical for career advancement. Finding these opportunities may be easier than expected, especially at institutions like Columbia, where experts from diverse fields are often just down the hall.