Stacy Malaker isn't married to her work, but she did discourage her graduate students from texting any interesting tidbits about the lab during her honeymoon over the summer.
"I saw one message, and I didn't respond," said Malaker, an associate professor of chemistry in Yale's Faculty of Arts and Sciences. "A ceiling tile came down. They took care of it."
Not that an errant tile could halt Malaker's scientific momentum one bit. In the five years since she established her Yale lab, she's made multiple breakthroughs in the study of large proteins called mucins, which are key biological players in the production of mucus. Mucins are O-glycosylated proteins, meaning they are sugar-coated proteins connected to oxygen atoms.
And they are involved, to some degree, in a host of diseases such as cancer, cystic fibrosis, and inflammatory bowel diseases.
Malaker's lab is at the cutting edge of techniques that apply mass spectrometry technology - an analytical process that measures the mass of molecules - to breaking apart mucins and seeing how they function in relation to disease.
In June, she was selected as a 2026 Camille Dreyfus Teacher Scholar, which comes with a $100,000 unrestricted research grant. Several months earlier, she received the David Y. Gin Award from the American Chemical Society's Division of Carbohydrate Chemistry & Chemical Glycobiology. Most recently, she was honored with the Society for Glycobiology's Significant Achievement Award. Such achievements speak to the trailblazing nature of her work.
Malaker spoke with Yale News recently about her research and what it's like to be at the forefront of an emerging field of chemistry. The interview has been edited and condensed.
Your research combines technical expertise in mass spectrometry with the search for new treatments and early detectors of disease. Which aspect came first for you as a scientist?
Stacy Malaker: During my Ph.D. at the University of Virginia, I worked with Donald Hunt, who is a very well-known for his biological research using mass spectrometry. Don's lab had been looking at phosphopeptides presented to the immune system for years, and he approached me about looking for glycopeptides that traverse the same pathway. I started by combing through old mass spectrometry data to see if the evidence was there, and when I found it, I embarked on a project to experimentally find more of them.
Which led you in a new direction?
Malaker: Yes, it led me to becoming a postdoc for [future Nobel Prize winner] Carolyn Bertozzi at Stanford. I was completely enamored with glycobiology, and the Bertozzi lab was looking for a postdoc that could do mass spectrometry at the same time they were interested in an enzyme that could cleave mucins.
The enzyme we found, called "sticky," or StcE, was the perfect way to break down mucins enough to apply mass spectrometry to them. It struck me that there had to be many, many other enzymes waiting to be discovered and characterized.
How far have you come since then?
Malaker: We've characterized about 10 mucinase enzymes at this point.
But there are tons of mucins - including potential biomarkers for ovarian cancer, pancreatic and colorectal cancers, Alzheimer's disease, and dry-eye disease - and tons of mucinase enzymes, some yet to be characterized, that break down those mucins.
What was technologically challenging when I was a postdoc has become pretty routine. We can now sequence a mucin, which had been near-impossible before.
How do you decide which diseases to target for mucin biomarkers?
Malaker: I like to say I'm disease agnostic and that anything we find that will have an impact, I will take it on. But I won't lie. Ovarian cancer is my white whale.
Beyond that, I'm excited about basic science and what drives me is a raw curiosity about what happens with these mucins at a molecular level. We're able to sequence mucins from the bottom up, but we don't know much about the crosstalk between different glycosites on a mucin, and we don't know what underlies those patterns.
Which mucins are important for immune modulation? Which ones occur simultaneously? There's a lot to do. We've climbed the first peak, but there's still a mountain ahead of us. That's the joy of research - especially in an entirely new field of research.
Ideally, what is the potential for this field? How could it help people?
Malaker: I think the most obvious clinical impact we could have would be in the detection space. For instance, the main blood test for ovarian cancer measures CA125, which is actually a mucin. And right now it isn't good enough to catch disease early, when it's most treatable. If we can figure out what the sugars on it look like in cancer versus healthy patients, we could build a much better test. The other area is therapeutic, since cancer cells coat themselves in mucins to hide from the immune system and our mucinases could potentially strip that coating off so immune cells can find the tumor and do their job.
But honestly, I think the basic science side is just as impactful. Mucins have been ignored for so long because they were too hard to study. So we're building tools that anyone can use, and that means labs all over the world can start asking questions about mucins that nobody could answer before.
One last thing. Is it true you carry a sugar molecule symbol with you wherever you go?
Malaker: It would be pretty hard to leave home without it! I got a tattoo of an oxane ring on my ankle, which is the backbone of most monosaccharides. I'd wanted a tattoo for a long time but could never decide what I cared about enough to put on my body forever, and then I got this job and dedicated my life to studying sugars, so it felt pretty appropriate.
