Insights From Immunologists: Professor Alan Ezekowitz

F4/80, clone CI:A3-1, is a well-characterized and extensively referenced macrophage and microglia marker. Recently, we had the honor of joining Professor Siamon Gordon, the father of F4/80, in celebrating its discovery over 40 years ago, alongside the past members of his lab who, in the decades since, have made significant contributions to macrophage research, and the scientific landscape as a whole.

We spoke to Professor Alan Ezekowitz, who undertook his doctoral studies in Siamon’s lab, about his diverse scientific career, which has included roles in academia, medicine, and industry. Alan became an expert in macrophages after initially becoming interested in these cells as a medical student and subsequently used his knowledge to develop a therapy for a rare condition in which macrophages are defective. 

Bio-Rad (BR): When did you first become interested in a career in science?

Alan Ezekowitz (AE): I went to medical school in South Africa and we had very strong clinical training, but we didn't have good basic science training. I knew about diagnosing diseases, but I didn't understand the pathophysiology of the diseases, and I didn't have the language or the vernacular to ask intelligent questions. So, I decided to go to the Sir William Dunn School of Pathology in Oxford to do a DPhil with Siamon Gordon so that I could equate myself.

I always thought I wanted to have a career that mixed both clinical medicine and basic discovery. Research gave me the opportunity to delve deep into basic mechanisms, which you can then apply to disease.

BR: How did you become interested in macrophages?

AE: I became interested in macrophages when I was a medical student. I did an elective at the Royal Brompton Hospital with Professor Margaret Turner-Warwick. She was interested in macrophages in the lung. So, while working with her, I became interested in lung macrophages and macrophage activation.

I always wanted to go to Oxford, so I found Siamon, who was working with macrophages there, and I wrote to him. I didn’t realize he was also from South Africa, and we actually met in Cape Town as he was spending his summer there. And that’s how I ended up in his lab.

BR: Can you tell us about your current research/role?

AE: Well, after I got my DPhil, I went to Harvard Medical School. I founded my own lab there and worked on innate immunity. I was eventually appointed as the Head of the Massachusetts General Hospital for Children.

Then I went to industry and I worked with Merck. I ran a franchise that covered several therapeutic areas all the way from very early discovery to applications of products as well as sales and distribution.

My current job is as an Advisory Partner at Third Rock Ventures, a venture capital firm that has invested in over 60 biotech companies.

BR: Can you describe a highlight from your career?

AE: When I was at the children’s hospital in Boston there was a 14 year old patient who came in with respiratory failure. What was unusual was that he had a fungal infection of his lung and that only happens if you are immunocompromised. So, I wondered whether he had a defect in macrophage activation and, if so, whether we could treat his cells with interferon-gamma (IFNy) and correct that problem. We did that, it activated his macrophages, and he was able to fight the infection.

 The disease he had was called chronic granulomatous disease (CGD) and we organized a multinational clinical trial in which I was the principal investigator. We showed that after one year, around 80% of the patients that received IFNy were free of serious infections versus only 30% in the control group (International Chronic Granulomatous Disease Cooperative Study Group, 1991). It was then approved by the FDA as a therapy.   

BR: What advice would you give to early career scientists?

I think for early scientists, you have to understand the new computational biology and how to ask the right questions going forward. I did clinical medicine and basic science, but now computational science is a whole other discipline and you need to make use of it. But you always have to get back to asking a fundamental question and how that question applies to human disease and the human endeavor. That’s why Siamon is so good, because he really understands pathology and tries to think about things as they apply to diseases. There’s no point in doing something just for the sake of doing it.

Thank you, Professor Alan Ezekowitz, for sharing your impressive career journey and practical advice with us, and helping to inspire the early career researchers who read Lab Crunches!