Research Spotlight: Hao Wu, PhD

Hao Wu, PhD, an associate research scientist in Dr. Xin Zhang’s lab, joined Columbia in May 2019 as a postdoctoral research scientist. During his time in the Zhang lab, he studied the molecular mechanisms that regulate eye development and how disruptions in signaling pathways can lead to congenital eye diseases. One such condition is Peters anomaly, a rare disorder characterized by abnormal development of the front portion of the eye, often resulting in corneal opacity, impaired vision, and glaucoma.

Together with his colleagues, Dr. Wu, alongside co-first author Yingyu Mao, PhD, recently published their study, “ABL kinases regulate FGF signaling independent of CRK phosphorylation to prevent Peters anomaly type II” in Nature Communications.

Following the completion of this project, Dr. Wu will depart the Zhang lab on June 30, 2026, to join a clinical pathology laboratory, also at Columbia. In this new role, he take on the new challenge of molecular epidemiology, focusing on pathogen surveillance, outbreak investigation, and disease monitoring, in collaboration with the New York State Department of Health and the New York City Department.

As co-first author of this study, Dr. Wu shares with us details about his research journey and this recent scientific achievement.

Tell us about yourself. How did you first become involved in developmental eye research?

My interest in research began during my Ph.D. training, where I studied autism spectrum disorders and Fragile X syndrome. Using genetically engineered mouse models to study how genetic mutations affect synaptic plasticity and neural development. I want to continue my studies in developmental biology and translational research. That interest ultimately led me to developmental eye research, where the eye is an elegant model system for studying complex developmental processes and disease mechanisms.

I was drawn to the Zhang lab because of its internationally recognized work on eye development and FGF signaling. The research combined genetics, developmental biology, and disease modeling, which aligned well with my background in mouse genetics and molecular biology. In the lab, I contributed to multiple projects involving both the lens and retina.

What are the main innovations and outcomes in your paper “ABL kinases regulate FGF signaling independent of CRK phosphorylation to prevent Peters anomaly type II”?

One of the major innovations of this study is that it challenges a long-standing model of ABL kinase signaling. Previous studies suggested that ABL kinases primarily regulate cellular functions through direct phosphorylation of CRK proteins. Our work demonstrates that ABL kinases instead regulate FGF-dependent eye development through a previously unrecognized PTPN12–p130CAS pathway, rather than through direct CRK phosphorylation. We further show that this pathway controls cytoskeletal dynamics and tension during lens vesicle separation, a critical developmental event in lens morphogenesis.

These findings identify ABL kinases as critical regulators of FGF signaling during eye development, reveal an unexpected mechanism by which they influence lens morphogenesis, and provide new insights into the molecular basis of Peters anomaly type II, establishing a framework for understanding how signaling pathways coordinate tissue morphogenesis. One of the defining features of Peters anomaly type II is the failure of the lens vesicle to properly separate from the surface ectoderm during embryonic development, and our study identifies a molecular mechanism that regulates this separation process by controlling cytoskeletal tension within developing tissues. By clarifying the underlying biology of the disease, this work provides a foundation for future studies aimed at developing therapeutic strategies for congenital anterior segment disorders.

How did you come up with the idea to research the ABL kinases’ function and influence on FGF signaling, and more broadly Peters anomaly?

The Zhang lab has long been interested in understanding how signaling pathways regulate eye development and how developmental defects lead to congenital eye diseases. FGF signaling has been a central focus of the lab’s research for many years. This study expands that work by identifying ABL kinases as important modulators of FGF signaling and revealing how signaling pathways are integrated with cytoskeletal regulation to control tissue morphogenesis. The findings contribute directly to the lab’s broader goal of understanding the molecular mechanisms underlying eye development and disease.

This was a large collaborative project that was already underway before I joined the lab. I was fortunate to become part of the project and contribute to the experimental work and data analysis. One of the most rewarding aspects was helping to uncover unexpected findings that ultimately reshaped our understanding of how ABL kinases interact with FGF signaling during eye development.

What roles did you and your co-authors each play in writing this paper?

This project was truly a team effort involving scientists with complementary expertise. The co-first author, Yingyu Mao, first generated a mouse model suggesting that Crk phosphorylation is dispensable, while I eventually showed that Abl kinase controls Crk activity not through direct phosphorylation but through the PTPN12–p130CAS pathway. Other co-authors also contributed technical expertise, data analysis, and scientific insights that helped advance the project.

Since the Zhang lab is the only developmental biology lab in the department, what were some of the unique challenges of this project? Were there any results that were particularly surprising or were a turning point for the project?

One challenge was the highly interdisciplinary nature of the project. Understanding developmental processes requires integrating genetics, cell biology, molecular signaling, imaging, and disease modeling. In addition, developmental studies often depend on precisely timed embryonic samples and genetically engineered mouse models, which require long-term planning and coordination. Fortunately, the collaborative culture within the lab and our external partnerships provided access to diverse expertise and resources that helped us overcome these challenges.

One of the most surprising findings was that mutating the known ABL phosphorylation sites on CRK and CRKL did not produce the developmental defects that existing models would have predicted. This result was initially discouraging for us because it overturned our presumptive model on ABL function in lens development, but it ultimately led to the discovery of the PTPN12–p130CAS pathway that is central to the paper.

Is there a particular aspect of the paper you are most proud of?

I am particularly proud that the study uncovered a mechanism that was both unexpected and biologically meaningful. Scientific progress often comes from challenging existing assumptions, and our findings prompted a reevaluation of how ABL kinases regulate CRK-associated signaling. Contributing to a discovery that advances our understanding of developmental biology and disease mechanisms was especially rewarding.

As you move into the next chapter, how does your past research experience and work in the Zhang lab translate to your new position in clinical pathology?

My primary role in the clinical pathology lab focuses on molecular epidemiology. I will work on projects involving molecular characterization of pathogens, genomic analysis, and epidemiological investigations. Although developmental biology and molecular epidemiology address different scientific questions, they share a common foundation in molecular genetics. My previous work taught me how to investigate complex biological systems, develop rigorous experimental strategies, and interpret large datasets. These skills are highly transferable to infectious disease research and molecular epidemiology. In addition, my experience working across disciplines has helped me adapt quickly to new research areas and collaborate effectively with scientists from diverse backgrounds.