the music of medicine: dr. shernan holtan

In September of 2024, The 11 Day Power Play–a public charity raising funds for cancer research in Western New York–presented Roswell Park Comprehensive Cancer Center with the opportunity to land a $1 million Team Science Grant to pursue innovative cancer research. In November, the five Roswell Park teams that had applied for the grant were whittled down to a winner–a team of researchers, led by Dr. Brian Betts, focused on novel treatments for acute myeloid leukemia.

Dr. Shernan Holtan–Chief of Blood and Marrow Transplantation at Roswell Park and a member Dr. Betts’ team–reveals the unlikely source of the team’s bold new research.

“Dr. Betts discovered that there’s a certain marker on cells that cause transplant problems, which means that we can pick those cells out of the blood, we can target them,” Holtan says. That marker is a protein called CD83, easy to detect on immune cells.

“Interestingly,” she continues, “Dr. Betts’ daughter asked him one day, ‘Hey dad, do you think that protein could be on leukemia cells, too?’ And he said, ‘I don’t know–I never thought of that!’ He went back to the lab, and lo and behold, it’s expressed on multiple types of cancer.

“So this new grant is going to fund the first in-human clinical test, to see if we can target that protein with CAR T-cell immunotherapy. This is huge, and truly exciting.”

It’s been a long road for Holtan–one that leads from the cornfields of the American Midwest to the chilly climes of Minnesota and, ultimately, to Buffalo and Roswell Park. Along the way, her twin passions–biology and music–battled for predominance in her life before arriving at a detente.

Holtan grew up in Nebraska: “Picture Little House on the Prairie–remember that show? That’s what it looked like where I grew up,” she says. “It was very rural. Kindergarten through eighth grade, we were all combined in one school, with eight to ten people per class. This was the 80s. There wasn’t that much to do, except wander through cornfields and say hello to cows,” she laughs.

In what would become a recurring theme throughout her life, Holtan turned to the world of the mind for entertainment.

“Going to the library and checking out books became a big thing for me, and listening to the radio–we didn’t have cable or anything like that. I started gravitating toward books about biology in general, and books about the body. I thought it was really cool.”

While Holtan was in high school, her father, then in his mid-30s, developed an autoimmune disease that made it impossible for him to walk. “That was devastating to watch, and that experience really led to me being bothered by the immune system, because of the effect it had on his life and by extension all of ours, as a family,” she says. “Remarkably, he didn’t pass away until last year. He was a woodworker, a cabinet-maker, and he was able to do that right until the end.

“He was also a huge progressive rock fan, and we spent a lot of time listening to albums together–every Pink Floyd album, every Rush album. We shared this passion for music, really deeply.”

Asked if she sees a correlation between her love of science and biology and her love of progressive rock, a sound steeped in music theory, one that blends art, emotion, math, and science in a very tangible way, Holtan reflects on the overlap of those two passions.

“I think there definitely is a correlation there,” she says. “That music has long, complicated songs with lots of layers, and a deeply thoughtful process going into its creation. There’s going to be interesting math with that, as well. I was good at math, and I was good at music, and so I could put those together.”

m. dellas

Holtan found her way to medicine, studying the immune system and contemplating in particular the complicated immune problems that can arise during transplantation. Always aiming to honor her dad through her work, she fixed her gaze on mitigating life-threatening immune-based complications of cancer therapy.

“Fortunately, throughout the years, I’ve been able to get back to music as well,” she says.  “This is one of the weird pandemic-time blessings–I bought a bass guitar off of Craig’s List, and bass was never my instrument. I was a pianist. I wasn’t going out or doing any normal social things during Covid, so I just sat down with my favorite songs and started to learn how to play.

“I would love to be in a full-time band,” she laughs. “But I already have a full time job!”

Music has become a space Holtan can visit when she needs to process the day-to-day of her work life.

“This is an intense field,” she says “We’re faced with a lot of death, side effects, toxicities. So to have the music as something to look forward to in the evening, one side of my brain gets to take a break. For example, as soon as my dad passed away, I said, ‘Well, I’ve gotta play some Rush now.’ So I dive into some of his favorite songs, and he’s there with me.

“We all need an outlet. We can’t be scientists, or whatever it is we do for a living, every minute of every day. Music gives me balance.”

Holtan still lives part of the time in Minnesota, where she’s resided for twenty years, with her husband and two children.

“When Brian came to Roswell Park, he wouldn’t stop calling me, saying, ‘You have to come here!’” she recalls. “I put him off for a long time, because I was taking care of my dad. When he passed, I still wasn’t prepared to move because my kids were in high school. So I’m still commuting, but it works well. My daughter is a freshman and my son is a senior and looking at colleges in Buffalo, so hopefully he’ll be out here next year. We’re split between two homes, but it’s working.”

One year into her employment at Roswell Park, Holtan has grown increasingly fond of the Buffalo region.

“I love Buffalo,” she says of her part-time home. “The people make it what it is. I’m very comfortable here. It reminds me of the midwest, honestly. And the work is very meaningful. To be able to partner with such great friends as Brian, to reshape a whole program and watch that unfold as we guide it into a new era, has been incredibly fulfilling.”

Transplant practices have changed substantially over the past few years. When Holtan started her work in the field two decades ago, roughly half of transplant patients ended up with a complication called graft-versus-host disease, where the transplant donor’s immune system attacks the body of the recipient. Many of those patients affected by the disease were likely to die from it.

“When you see that you’re losing a fifth of your patients over a year, it’s devastating,” she says. “So we’ve been working really hard to find ways to mitigate that risk.”

When Holtan was pregnant with her son, it struck her that her own body was host to someone at most just half-matched to her genetically–why, she wondered, wasn’t there a negative immune reaction like the ones she saw in patients with graft-versus-host disease?

That “crazy idea,” as Holtan describes it, led her to study the immunology of pregnancy. Her research revealed that pregnancy hormones are a powerful immune modulator and she began using them to treat GvHD.

“It took me a decade to convince someone to give me the grant to do it,” she says, “but when I did eventually get that grant, clinical trials proved that it did indeed work. Now, people all over the world do it–it’s been incredible to get emails from people around the world saying ‘thanks for this idea–we tried it out and it worked!’”

Holtan also co-led a phase III clinical trial for a new method of preventing GvHD that involves the administration of immunosuppressant chemotherapy to transplant patients. The trial yielded positive results–Holtan and her team found that this treatment vastly outperformed standards of care that had been in place since the 1980s.

The most rewarding piece of these two groundbreaking clinical trials, Holtan says, is the fact that the treatments are not only effective but highly accessible.

“We didn’t need anything fancy to do this,” she says. “Both of these trials involve inexpensive, established drugs. Low and middle income countries can do this. It’s not just for the wealthiest communities, it’s not just for the people who have the best resources. It’s for everyone.”

Today, a transplant patient’s risk of dying from graft-versus-host disease is significantly lower than it was when Holtan began her career–and her own creative thinking and drive to act on the ideas it fosters have played a role in generating those improved outcomes.

She’s continuing to help shape the immunology landscape in her own ongoing research and clinical trials–looking for alternatives to immune suppression for the prevention of GvHD–and as a member of Dr. Betts’ research team.

“Life helps us, if we’re open to it,” Holtan reflects. “My son gave me the idea to explore pregnancy hormones. Dr. Betts’ daughter gave him the idea to look at leukemia cells. We’re lucky to have had people give us the right ideas at the right time, and to have been receptive to them.

“It’s not like genius comes from the lab and the data alone–it also just comes from life, talking to people and having conversations, and being open.”