Lauren Hill made the layup.
It was the shot seen ’round the world. In 2014, Hill seemed to be on every news and sports program in the country when the former high school basketball standout played in one game for the college that recruited her, Mt. St. Joseph’s. The game was moved up so she could play before she died.
On the court, the ball was passed to Hill, #22. Turn, half step, left-handed layup, swoosh. Along with the millions of others who watched that video clip was Jessica Cummings, Lauren’s cousin. She was in high school at the time.
Fast forward a few years. Cummings saw a post on the Facebook page of the pediatric brain cancer research nonprofit The Cure Starts Now that mentioned Dr. Carl Koschmann, one of the country’s leading researchers and clinicians studying diffuse intrinsic pontine glioma (DIPG). It was the type of tumor that took Lauren’s life. The type of tumor that took the life of Chad Carr, the young grandson of former U-M football coach Lloyd Carr and the namesake of the #chadtough movement and foundation. The type of tumor for which there was no cure.
She reached out to Koschmann. “Initially, I just wanted to say thank you on behalf of me and my family for everything that he’s done,” says Cummings. “It turned out he had lab positions open.”
Cummings had recently completed her undergraduate degree in kinesiology, with a heavy concentration of neuroscience classes at LSA. Given Cummings’s experience in studying intraoperative neuromonitoring, along with her desire to become a pediatric oncologist, Koschmann saw an opportunity. He asked her to join his lab.
Initially, Cummings wasn’t sure what to do. She intended to go to medical school, which would lead to significant debt. Other job offers in intraoperative neuromonitoring would have given her a higher salary and more security.
Still, she was driven to find a cure for the cancer that had taken her cousin’s life, and she accepted the job in Koschmann’s lab. Working in the lab one night, she began feeling doubts about her decision. “Then I looked down at my watch to check the time, and—because I’m a weirdo and use military time—it read ‘22:22.’ The next night, the same thing,” she wrote on Facebook. “I think someone may have been telling me to stay put.”
That “someone,” of course, was her cousin Lauren. #22.
Cummings is one of many undergrads and recent graduates, most from LSA, who have worked in Koschmann’s lab on the U-M medical campus. They aren’t there just to clean test tubes or prep pipettes; regardless of their year or level of experience, Koschmann makes them an integral part of the team. They coauthor research papers that appear in prominent journals, study different combinations of medications, look at lab samples, and meet with patients alongside Koschmann. He asks for their thoughts about recently published journal articles—not as an academic exercise, but because he wants to learn from their insights.
“I don’t know what other PIs [principal investigators] do, but what I’ve found is that if you can get the students really engaged to the level of understanding and some autonomy, they’re much more willing to put in more hours and come to lab hours,” says Koschmann, the first ChadTough Defeat DIPG Research Professor of Pediatrics at Michigan Medicine, the University of Michigan’s academic medical center. “These students are so much more impressive than I was at their age.”
He adds, “Our lab is a very supportive culture. The students get to see the trainees who are medical students, then residents, then fellows, then physicians who are running the lab. They can see what it looks like to be at each of those steps.”
Research by Koschmann and colleagues at Michigan Medicine has helped to advance the understanding of DIPG and related brain cancers in recent years. The pace of research and discoveries has been boosted by an infusion of research funding and national attention related to DIPG following the 2015 death of five-year-old Chad Carr and the founding of the ChadTough Defeat DIPG Foundation.
The statistics are jarring: Brain cancer kills more kids than any other type of cancer, and DIPG represents 10 percent of all pediatric brain tumors but nearly 50 percent of all pediatric brain cancer deaths.
“It’s too much sometimes, when you think of what these kids are going through,” says Seongbae Kong, who earned a B.S. in biochemistry in LSA in the spring and continues to work in the lab during a gap year before medical school. “We have a patient with a glioma [brain tumor], and she’s in college and wants to go to med school. Now that’s all on hold. It really got to me that day, thinking, ‘that could’ve been me.’”
That’s what fuels him to work diligently in Koschmann’s lab, where DIPG is being attacked and studied in a wide variety of ways. “There are always new ideas being pushed forward in the lab. It’s such a cool work environment where we get to look at new ideas and immediately see what’s feasible, even as undergraduates,” Kong says. “Carl really wants to hear what we have to say.”
He wants to hear it, even if the student is an 18-year-old in their first year of college. “Carl knows that anybody who can add anything can be valuable—even if it’s me, as an undergrad,” says Sana Sharba, now a second-year LSA student, who started working in the lab during her first year. “It’s a big puzzle to solve, and every person who comes into the lab has a voice.”
That’s why they work long hours in the lab, working with cell lines and fusion proteins, studying animal models, and even the heartbreaking task of getting consent from parents for an analysis of the child’s brain to be conducted once they have died.
A cure isn’t necessarily the only collective goal of these undergrads and the other researchers in the lab. They’re also working to make a difference in patients’ and families’ quality of life. They are exploring treatments that prolong a child’s life, or make them more comfortable when their bodies are failing.
“I want to make a child feel a little bit better, in the crappy circumstances that they’re in,” Kong says. “That’s what I hope for.”
One lab member, Karthik Ravi, created an app that is being used by clinicians around the country to determine the best drug combinations for patients with brain cancers. Ravi was a high school sophomore in the miRcore educational outreach program when he first met Koschmann. Ravi already knew that he wanted to be a scientist, but Koschmann’s talk shaped and honed his plans.
“He talked about liquid biopsy, the idea that a brain cancer patient’s tumor might shed some of its content to blood or urine, and that the tumor could be detected in that way,” Ravi recalls. “That idea blew my mind.
"I talked to him afterward and told him I’d be honored to work in his lab.”
When Ravi began his undergraduate studies at LSA, he was already an experienced researcher, having honed his interest in personalized medicine under his miRcore mentor, Dr. Inhan Lee. Ravi, who became vice-president of miRcore and gave lectures about how a patient’s genetics can be used to develop tailored treatments.
As a biology major at U-M, he began working in Koschmann’s lab, just as he had telegraphed a few years earlier. Koschmann introduced Ravi to a simple algorithm that his team had developed as a way of helping clinicians select the optimal targeted therapy for brain cancer patients. Ravi saw the potential for something much bigger.
“My goal was to make it accessible outside of U-M, scale up the number of drugs in it. I helped to lead translation of the centralized spreadsheet to this more accessible web-based version,” Ravi says. Ravi applied for and received $100,000 from the Chad Carr Pediatric Brain Tumor Center to pay for a team of web and app developers. The web-based algorithm is now called CNS-TAP, and it is in use around the nation. An international consortium also adopted the platform for use in high-grade pediatric brain cancer clinical trials.
CNS-TAP has made a difference in how some patients are treated—even before cofounder Ravi graduated in 2022 with a biology degree from LSA.
A child in California was being treated for brain cancer, and the child’s case went before a tumor board that would decide on which medication to use. The conventional wisdom would have had them taking dasatinib, one of a class of medications called kinase inhibitors that is used in the treatment of leukemia patients and has been repurposed to treat some brain cancers.
Members of the tumor board had read a recent paper published by Koschmann, Ravi, and numerous colleagues in which they reviewed the effectiveness of dasatinib and 26 other drugs. They found that a different medication, ponatinib, actually crossed the blood-brain barrier significantly better than dasatinib.
“They reviewed our results, reconsidered, and went with ponatinib,” Ravi says. “It was really meaningful to see how they changed their decision based on what we had discovered.”
Ravi has won a slew of awards and fellowships, including the Churchill Scholarship that will allow him to study for a year at Cambridge. Then, he’s off to medical school, with hopes of becoming a researcher-clinician. “The DIPG work has exacerbated my passion for liquid biopsies,” he says. “We need better ways to diagnose and to monitor the tumors’ response to treatment. The fact that the prognosis for DIPG is so dismal is definitely a motivating factor.”
The use of liquid biopsies was the idea that first drew him to working with Koschmann. Does it still blow his mind, as it did when he was a high school sophomore? “It does,” Ravi says. “Every day.”
Some of the children who have had DIPG were diagnosed at age five, some not until their late teens. Some had gap-toothed smiles and wore princess costumes; others had just started wearing eye shadow. One wanted to go fishing in her final days. One wanted to buy his mom a ring with a red stone.
Nearly all died within two years of diagnosis.
“What really struck me is just how little time these kids have,” says Clarissa Babila, who is set to graduate in December 2022 with a B.S. in molecular, cellular, and developmental biology. She has worked in the lab since her first year at LSA. “Once they are diagnosed, they don’t have a lot of time to receive treatment that will improve their quality of life.”
DIPG tumors start in the brainstem, which makes them nearly impossible to remove surgically. The disease is also notoriously difficult to diagnose because obtaining a biopsy from the tumor could result in damage to the parts of the brain that are still functioning well. That’s why liquid biopsies, such as the ones Ravi and others in the Koschmann lab have been studying, are a promising approach for the future.
Earlier in his career, Koschmann saw patients who had cancers such as leukemia. The blood cancer can have a devastating effect on people, and its death rate remains significant. Still, leukemia has been studied more thoroughly than DIPG, and many patients survive beyond the five-year mark once known as remission.
Alyssa Wierzbicki was Koschmann’s first patient after his fellowship. Her little brother remembers Koschmann walking in to talk with the family for the first time, wearing his trademark orange-framed glasses and orange sneakers. The siblings always laughed when they met with the physician, in spite of the seriousness of her diagnosis.
“One thing that really stuck with me was my sister’s health care team didn’t just focus on my sister’s health,” recalls Kyle Wierzbicki, the little brother, who was in middle school at the time. “I remember very clearly Carl’s care. He has a very special way of dealing with patients and connecting with them on a personal level. He feels like a friend. He gave my parents his cell phone number so he could really be there for us.”
The experience led Wierzbicki to start a cancer research club in high school that partnered with the Stand Up to Cancer charity. When he was accepted at U-M, he contacted an old friend.
“Carl offered me a spot in his lab,” says Wierzbicki, who graduated in 2021 with a B.S. in molecular, cellular, and developmental biology at LSA. He was especially drawn to the promise of precision medicine, in which a patient’s genetic information can be used to develop personalized therapy.
“I think there’s going to be exciting progress in the next couple of years. Hopefully a big breakthrough—some genetic mutation we can target, some new chemo treatment,” Wierzbicki says. He wants to be a part of that progress with his current studies at Weill Cornell Medical College and beyond, and to see DIPG patients get a second chance, and to recover from cancer, just like Alyssa did.
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