Taming the Rogue Protein
EMU chemist’s custom molecule may be a key to treating fibrotic disease
Taming the Rogue Protein
EMU chemist’s custom molecule may be a key to treating fibrotic disease
Cory Emal, Ph.D., professor of chemistry, pursued the perfect molecule for 20 years, but he wasn’t just looking for it. He was looking to create it.
Emal had taken up the challenge of building a molecule as part of a collaboration with Daniel Lawrence, Ph.D., professor of internal medicine at the University of Michigan and founder of MDI Therapeutics. Lawrence’s research was focused on a protein, plasminogen activator inhibitor-1 (PAI-1), which is important to the body’s wound-healing process. But PAI-1 sometimes goes rogue and is over-produced, causing tissue in the body to harden or scar and in some cases inhibit the function of organs including the heart and lungs. Emal’s role was to create a molecule to mitigate those over-produced proteins, and potentially create a more effective drug to treat fibrotic disease.
But the rogue protein wasn’t making it easy.
“PAI-1 flexes and moves in a lot of ways that we don’t completely understand, so that gives us an incomplete picture of the shape of the protein,” Emal says. “If you think of it being a key in a lock, we wanted to design the key that fits the lock of the protein.”
Without a clear visual, Emal likens the process of getting the right fit to feeling around in a pitch-dark room.
“We’re really just waiting for someone with a flashlight to show up,” he says, “or to find a door into the next room—that opens up a lot more possibilities as well.”
Finally, after nearly two decades of bumping around, the molecular key fit. The lock turned, the potential of Emal’s molecule garnered research funding, and in June 2024, a first-in-human (phase 1) clinical trial was begun to evaluate the safety and tolerability of the new molecule, MDI-2517, in healthy volunteer participants.
“It’s incredible,” Emal said of the trial. “I can’t overemphasize how exciting it is.”
The excitement comes after years of altering “base” molecules with a series of chemical reactions that can alter the molecules’ features. The chemical compounds used are typically purchased from companies that offer hundreds of thousands of options, so researchers like Emal can try, try again...and again.
“The narrowing down is enormous,” Emal says. “Our lead compound came from a library screen of about 150,000, and that screen gave us two leads. We were able to narrow down from 150,000 to two in one step.”
A custom molecule two decades in the making, EMU chemistry professor Cory Emal’s research holds life-changing potential.
A custom molecule two decades in the making, EMU chemistry professor Cory Emal’s research holds life-changing potential.
From there, Emal’s lab made roughly 400 new compounds trying to improve on those two hits.
“And we did,” Emal says, “about 300 compounds in. It sort of floated to the top, and that’s the one in the clinical trial.”
Emal notes that in drug development getting to the human trial stage is always the goal, but the odds are against it.
“Pharmaceutical companies spend billions of dollars every year trying to do this, so there’s no particular reason to think an Eastern Michigan professor, undergrad lab assistants and a seasoned academic from U of M could pull it off.”
The participation of undergrads in such impactful research is unusual, and is one of the advantages of an EMU education, Emal says.
“If you’re an undergraduate who wants to be involved in scientific research, you’re certainly going to have one-to-one attention from your professor at Eastern, and you will almost certainly not at a big research school.”
“If you’re an undergraduate who wants to be involved in scientific research, you’re certainly going to have one-to-one attention from your professor at Eastern, and you will almost certainly not at a big research school.”
— Corey Emal
Now that the clinical trial is underway, Emal’s other passion, EMU’s fermentation science program, will also have his attention. He and chemistry colleague Gregg Wilmes co-created the program in 2014, and rolled it out two years later. Since then, the program has won the 2024 U.S. Open College Beer Championship, and spawned professional brewers.
“One of our graduates has two Eastern science degrees, now teaches in the program and is a head brewer at Ypsi Alehouse,” Emal says, noting another has been hired on at Brewery Becker in Brighton.
“I know the owner of that brewery very well, and he has high standards,” Emal says. “So the fact that he hired one of our graduates, that means something. It makes me very happy.”
By Amy Campbell
Photos by Charlotte Smith