Moustafa Gabr, PhD: How A Chemist Uses Imaging to Bridge Therapy and Diagnostics

Moustafa Gabr, PhD, recently joined the faculty of the department of radiology at Columbia University Irving Medical Center and is a new member of the Tumor Biology and Microenvironment (TBM) program of the Herbert Irving Comprehensive Cancer Center (HICCC). A chemist by training, Gabr is drawing on his foundation in chemistry to develop a new class of compounds that could both help visualize cancer and deliver cancer treatments. 

Can you tell us about your background and research interests?

I have been interested in science from a young age, inspired by my parents, who are both pharmacists. Watching them prepare medications in the pharmacy sparked my interest in discovering new drugs to help patients. 

During my training in pharmaceutical science, I became passionate about using chemistry to understand and influence biology, which led me to pursue a master’s degree and PhD in chemical biology. I then completed my postdoctoral training in radiology at Stanford University, where I focused on translating these approaches toward clinical applications. 

As a chemist, I became particularly interested in immunomodulation- using small molecules and peptides to influence the immune system and develop new approaches to both imaging and treatment. I established my lab at Weill Cornell Medicine about five years ago and joined Columbia and the HICCC earlier this year. 

How does a chemist end up in a department of radiology?

My interest in imaging and its applications to developing new therapies began with a broader question in precision medicine: how can we understand the specific biological targets that are driving treatment resistance or suppressing the immune system in an individual patient? 

To answer that, we need ways to see those targets in the body. That led me to the concept of theranostics, or developing agents that can potentially be used for both therapeutics and diagnostics. This is a very promising area for using imaging. 

At Stanford, I focused on PET imaging and developing tracers that could visualize the expression of specific targets. At the same time, I became interested in whether those same chemical entities could be designed to modulate the target. 

That idea is central to my lab. We have a diagnostic side focused on developing imaging agents and a therapeutic side focused on modulating biological functions. Our goal is to bridge those two areas and develop compounds that can potentially serve as both diagnostic and therapeutic tools. 

Can you give an example beyond PET imaging of what theranostics are? 

One of my favorite examples is VISTA (V-domain Ig suppressor of T-cell activation), an immune checkpoint that can suppress immune activity. We became interested in it because patients can develop increased VISTA expression in response to PD-1 inhibitors, which may contribute to treatment resistance. Being able to see that change could help us understand why a therapy is no longer working and identify new treatment strategies. 

Our goal was to develop a small molecule that could both visualize VISTA expression using PET imaging and block its function. We took the project from initial discovery through development of a PET tracer that can visualize VISTA, and we are now working to further develop its therapeutic potential. 

For me, this project captures the broader goal of our research: using chemistry to bridge diagnosis and treatment, helping us see what is happening in a tumor and, ultimately, find ways to intervene. 

What brought you here to Columbia, and what opportunities do you see at the HICCC for your research?

My research is highly multidisciplinary, and I sometimes think of my lab as a small company bringing together six areas: synthetic chemistry, chemical biology, molecular imaging, machine learning and AI, pharmacology, and immunology. Collaboration across these core areas is essential. 

What attracted me to Columbia was the opportunity to bring these disciplines together within a medical center, alongside clinicians already working directly in the areas we study. Being part of the HICCC gives us an exciting opportunity to connect discoveries in the lab with clinical research and, ultimately, patients. 

We’re also working to bring patient and clinical samples into the research process earlier, so we can think about the potential for translation from the very beginning, not just at the end. 

What does your multidisciplinary approach look like for the scientists in your lab?

When I recruit someone, I look for a person with strong expertise in one of our core areas who is also willing to learn another discipline out of the six I mentioned. 

For example, a synthetic chemist might learn chemical biology, or someone trained in pharmacology might explore immunology. That creates a multidisciplinary environment where people can contribute their strengths while also expanding their skill sets. It allows us to build projects collaboratively and move them forward more efficiently. 

There is an element of a startup or drug discovery company in this approach, but the academic environment is what makes it different. Training and mentorship are major priorities for me. I enjoy helping scientists develop beyond their initial training and preparing them for the next stage of their careers. 

What are your ultimate goals and vision for your research at Columbia? 

Over the past five years, we’ve developed several projects, with a major focus on glioblastoma, and have several candidates showing promising results in preclinical models and in 3D platforms. The next step is figuring out how to move these discoveries closer to clinical evaluation, including optimizing the compounds and understanding their safety, pharmacology, and other properties. 

You have a background in writing as well as science. How has that influenced you as a researcher? 

Yes, writing has been a passion of mine since I was young! Before I became a scientist, I was a professional writer and published several books and articles on a wide range of topics.

When I started my PhD, I stopped writing creatively, but I found writing papers and grants requires the same creativity, and I think creativity and scientific discovery are closely connected.

Now, my goal is to bring those two interests together: using chemistry and creativity to discover new ways to understand and treat cancer, while training the next generation of scientists to do the same.