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Mario Amzel on Protein Structure and Drug Design

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Mario Amzel on Protein Structure and Drug Design

Inteviewed by Catherine Gara

Mario Amzel on Protein Structure and Drug Design

Mario Amzel directs the Department of Biophysics and Biophysical Chemistry. He studies the physical characteristics of biological molecules.

How did you get into science?

AMZEL: Math was actually my preference, but when I told my father I was going to study math in the university, he nearly had a heart attack. He thought it was too impractical. So we compromised and I studied chemistry. This was in Argentina, where I grew up. I started doing research there when I was still an undergraduate and then did my Ph.D. in physical chemistry. I came to Johns Hopkins for a postdoc in biophysics, and I’ve been here ever since.

You study individual molecules to a high degree of detail. How does your research relate to human health?

AMZEL: Drug development has improved over the years, but success rates will continue to increase as biophysics plays a greater role in the process. Almost all medicines interact with specific proteins in the body to change the way they work. Proteins each have particular shapes, sizes and other physical properties, and these properties allow them to complete tasks in the body.

For most of human history, we could only stumble upon new medicines that happened to interact with misbehaving proteins, but now we have the ability to design medicines that interact precisely with targeted proteins. As a biophysicist, my job is to learn as much as I can about the structure and function of a protein. Then, pharmaceutical companies are better suited to make a drug to interact with that protein. They can also search large digital “libraries” of existing compounds to see which might interact. Then the biological tests can begin.

What is an example of a protein you’ve studied?

AMZEL: PI3K is a part of the body’s hormone signaling system. It is activated by insulin and other molecules. Once it’s turned on, it sends signals that ramp up cellular processes, like survival, growth, division and mobility. Bert Vogelstein’s group found that PI3K is mutated in the cancers of many patients so that it is abnormally active. This, of course, helps those cancer cells survive and grow. My lab is working with Sandra Gabelli’s to learn how PI3K is activated normally and how cancer mutations activate it irregularly. We’ve figured out PI3K’s structure, and that gave us hints about how it adjusts its shape during activation. That information can then be used in computer searches for compounds that might prevent its activation or block its function after activation. Eventually, those compounds could become part of patients’ cancer treatments.

sunset on water A view from Amzel’s cabin.

What do you enjoy doing outside the lab?

AMZEL: My family has a small cabin on a creek off the Chesapeake Bay. I meet my daughters and granddaughter there almost every weekend. I enjoy kayaking and making brunch for them, or barbecuing when the weather’s nice. I also enjoy reading fiction, mostly in Spanish, and taking walks along the Inner Harbor near my house.

Taking Away Cancer Cells’ Advantage

Mario Amzel and his team are learning more about the proteins that give cancer cells an advantage over their healthy neighbors. Their work could lead to new therapies to block the proteins’ action.