"Chad winks"

By Madeline Swanson

“Rare” is a loathed word for any family with a child plagued by a brain tumor. “Rare” is one reason for so little funding and so few researchers studying tumors like Diffuse Intrinsic Pontine Glioma (DIPG), the deadly pediatric brainstem tumor that occurs almost exclusively in children under the age of 10. And while the condition is rare—there are around 350 new cases in the United States each year—that’s little consolation for the families stricken by its presence. With no viable treatment options, the condition is a childhood death sentence. And “rare” is one reason that the last four decades have generated little progress toward treatment.

That was until DIPG came for Chad Carr, the youngest son of Tammi Carr (AB ’97) and former Michigan quarterback Jason Carr (AB ’95), and grandson of former Michigan Football coach Lloyd Carr and former All-American Michigan safety Tom Curtis (AB ’70). Chad was diagnosed with DIPG in 2014; his diagnosis and death ignited a national movement. Today—over four years, thousands of donors, and millions of dollars later—researchers at U‑M are testing novel cancer treatments that may have promising implications for pediatric brain cancers like DIPG. Thanks to Chad and the Carrs, U‑M may finally push DIPG research forward after four decades of silence.

Leaders & Best sat down with the Carrs to learn how grassroots philanthropy is propelling that pioneering research forward. We also interviewed the husband-and-wife research duo behind one of the many promising new therapies emerging at U‑M. This is the story of a relentlessly inspiring Michigan family and the silent heroes bringing hope to families facing this deadly disease.

Silent Heroes

On a warm June morning in 2015, the Centennial Park and Farms subdivision bustled with activity. The normally serene neighborhood—tucked down a quiet road on Ann Arbor’s south side—was gearing up for its biggest event of the year. Tammi and Jason Carr busily gathered old clothes, toys, and other treasures for a neighborhood garage sale. Alongside 70 other Centennial Park families, the Carrs were preparing for the first official fundraiser for what would become The ChadTough Foundation. Following Chad’s DIPG diagnosis, the Carr family devoted their lives to raising money and awareness in hopes of finding a treatment and eventually a cure for the disease. This community garage sale would serve as the movement’s humble origins.

And at a home just around the corner from the Carrs’, the foundation’s first major gift was already awaiting. As Tammi tended to a sale, she saw a friend excitedly escorting a man through neighboring backyards toward her home. In his hand was a personal check.“I took the check, and it was Ron Weiser. I had heard the name, but I had never met him,” Tammi recalls. “He said, ‘I saw in the newspaper you guys were raising money at a garage sale, and I wanted to do something to help.’” Weiser helped by personally delivering a $10,000 check.

U‑M Board of Regents Chair Ron Weiser (BBA ’66) and his wife, Eileen (MMus ’75), are prolific philanthropists, business leaders, and ardent supporters of U‑M. They are among the top donors to the university, with the majority of their gifts benefiting the Medical School. Tammi knew that the Weisers were good people to have in her corner.

Tammi and Ron agreed to meet again the following week for coffee. They couldn’t have known then that their conversation would catalyze a worldwide movement aimed at treating and curing pediatric brain cancers.

Meanwhile, an internationally acclaimed team of scientists at U‑M was working to do just that. Maria Castro, PhD, and Pedro Lowenstein, MD, PhD, hold professorships in the Department of Neurosurgery named for Richard C. Schneider. The couple are professors of cell and developmental biology at U‑M’s Medical School.

Hailing from Argentina, Castro and Lowenstein married in 1988, eventually becoming research partners. With more than 40 years of combined experience in adult and pediatric brain tumors, for the past two years the couple have included DIPG as part of their genetic engineering studies to cure brain tumors. Their decades-long quest to cure malignant brain tumors has resulted in pioneering work in immunology and gene therapy that’s helped put Michigan Medicine at the forefront of research into malignant brain tumors. Most importantly, their work offers promise for the treatment of children.

An early catalyst for that work happened, ironically, in the buffet line of an event Castro and Lowenstein were attending. As they moved through the buffet line, a stranger asked Castro, “What would you wish for that would really help you with your work?” Two months later, Castro received a phone call. It was a development colleague calling with news that she had received an incredibly generous donation from a man Castro had apparently met in a buffet line. The donor had used his 60th birthday as an occasion to host a townwide barbecue to raise money for Castro’s work.

Much like Ron Weiser arriving in the Carrs’ backyard with a $10,000 check, a seemingly random act of philanthropy removed a barrier to progress, bringing Castro one piece of equipment closer to moving research forward.

Tammi has a name for serendipitous moments like these.

“We call them ‘Chad winks,’” she said. “Chad just puts the right people in our path. It’s amazing.”

In these disparate, ordinary moments in time, at garage sales and in buffet lines, Chad’s generous spirit is seemingly at work. The memory of Chad and children like him connects people to a cause greater than themselves.

The memory of Chad is strongest in his childhood home. As Tammi welcomed the Leaders & Best team into her home, I can’t help but notice Chad’s smiling face in family photos lining the shelves, consoles, and walls. Pillows and blankets displaying #ChadTough, the foundation’s Twitter hashtag, cover couches and chairs. #ChadTough signs spring from the front yard like daisies.

In this space, everything and everywhere is a reminder that a beautiful, energetic little boy was taken from his family before his time. But each fragment of that memory reminds us that his death wasn’t without purpose.

As Jason puts it, “If you wanted to make a change in this disease, you couldn’t have picked a more perfect kid.”

And DIPG was in desperate need of change.

The Death Sentence

In the United States, roughly 350 children are diagnosed with DIPG every year. The parents of every one of those children are told there is a zero percent chance that their child will survive the disease.

Unlike other pediatric brain cancers, this inoperable tumor spreads throughout a child’s brainstem—the highway that connects the brain to the rest of the body and controls all bodily functions. Since a child’s brain is growing, the targeted therapies often offered to cancer patients are too risky for children.

All too familiar with this terrible impasse is Karin Muraszko, MD, chair of the Department of Neurosurgery at Michigan Medicine and the Julian T. Hoff, MD Professor in Neurological Surgery at the Medical School.

“Most therapies target developing, growing, and multiplying cells, but if you do that in a child, you may kill some of the important brain pathways that are allowing the child to grow and develop,” Muraszko says. “Literally a millimeter deficit in [the brain] can leave you with neurological problems.”

As the tumor wages war on their growing bodies, families helplessly watch their children deteriorate. Their limbs grow increasingly weak. Their faces swell. Harsh treatments fatigue their tiny bodies. Their stride and speech abate as they fight for their lives, and then, suddenly—those lives, barely begun, are over.

There are many barriers to treating DIPG. Surgical removal of the tumor from the developing brainstem would kill the child immediately. Chemotherapy is ineffective. Radiation is especially toxic to children. Instead of traditional treatments, a highly advanced combination of therapies—from immunotherapy to genetic sequencing—is required to attack the inoperable tumor.

Nearly 60 years ago, astronaut Neil Armstrong’s daughter, Karen “Muffie” Armstrong, died of DIPG. Even such a high-profile death didn’t jumpstart funding and DIPG awareness. While the field of pediatric cancer research has seen a number of breakthroughs in recent years, DIPG has experienced little progress. In the U.S., only a sliver of federal research dollars are allocated to all pediatric cancers combined. And with so few children diagnosed with DIPG, little is known about the lethal tumor, leaving patients and families few options for treatment.

This was the case for the Carrs.

A few days before his 4th birthday, Chad fell and broke his nose, prompting a trip to the emergency room at C.S. Mott Children’s Hospital. After a basic examination, doctors sent Chad home and assured his parents that his nose would heal on its own. But it wasn’t long before Tammi and Jason noticed he was “a little off.” Convinced Chad had a concussion, they returned to Mott for an MRI.

The MRI was supposed to take only a couple of hours, but when nearly four hours had passed, panic began to set in for Chad’s parents. The doctors had found something, and they told the Carrs that Chad would be spending his 4th birthday in intensive care.

Tammi and Jason began bracing themselves for the worst, not knowing that the worst was beyond what they could imagine.

“You’re saying to yourself, ‘The worst thing could be cancer,’” Jason says. “So I’m gearing myself up for the fact that he’s going to have to undergo radiation or go right into surgery.”

After what felt like days, Valerie Opipari, MD, arrived alongside a team of doctors. Opipari is the Ravitz Foundation Endowed Professor of Pediatrics and Communicable Diseases and, at the time, was the chair of the Department of Pediatrics. As a close friend of the Carrs’, she wanted to be there in person to offer her support in what was to come. As Tammi and Jason anxiously hovered over a digital image of Chad’s brain, the doctors pointed to his brainstem.

“I just looked up and said, ‘Are you telling us he’s going to die?’” Tammi recalls, tears streaming down her cheeks. “They said, ‘The prognosis is about four to nine months.’”

The weight of those words knocked Tammi to the floor.

Planting the (Grass)roots of Change

Overwhelmed with unimaginable grief, Tammi remembers waking up the next morning with an epiphany and new sense of purpose.

“We have to do something. We have to make this big,” she declared to Jason and their family.

Tammi is a strong, incessantly energetic, positive woman: a “mama bear” she warns with a smile. When DIPG attacked her youngest son, she channeled her grief to rally a community of supporters who would help fight back with ferocious intensity.

Soon, something was in the air. As word spread of Chad’s diagnosis, family, friends, neighbors, and the community sprang into action. The ChadTough movement was born.

“I’ve barely asked anybody for anything. They just want to help,” Tammi says.

Shortly after Chad’s diagnosis, the Carrs created the ChadTough Fund at Mott to support pediatric brain cancer research. The fund has since received support from more than 1,500 donors, including many faculty and staff who were touched by the Carrs’ plight. ChadTough quickly gained steam within the local and U‑M communities, and before long, grew into a national movement: Chad was becoming the face of DIPG.

“The support we’ve had from our local community and the Michigan community… I don’t know how people go through what we’ve gone through without that,” Tammi says. “There are a lot of days I just want to crawl into bed, and some days I do. But when people give up their time, their abilities, and their resources—and they’re so passionate about it—that just keeps you going.”

When Tammi first met Ron Weiser, just months before the official launch of the ChadTough Foundation, she couldn’t have known the central role he and other philanthropists would play in the movement. The foundation was established in December 2015. “It was really as organic and grassroots as it comes,” she says. “It was never us saying, ‘We have to start this foundation.’”

“It was really more like, we can’t not start this,” Jason says. “It’s a disease that so deserves increased attention and support, so we said, ‘We have to do this.’”

But as Chad’s condition began to worsen, Tammi felt her window to “make this big” was narrowing. She knew that saving her own son would be impossible, but that philanthropic support would be crucial for helping other families like hers in the future. For Chad, the inevitable had become imminent. Breathing and swallowing were growing increasingly difficult. His speech was becoming sporadic.

On Nov. 23, 2015, Chad died at home in Tammi’s arms. He never learned how to ride a bike. He never graduated from kindergarten. He hadn’t yet grown big enough to toss the football with his brothers in his family’s backyard.

“There are terrible things happening every day in this world, and you always feel like you’re immune to it, but nobody is,” Tammi says.

Chad’s funeral service was held on Tammi’s 40th birthday. Grieving guests received a funeral card with John Alessi’s The Brave Little Soul printed on the back. The story tells of an angelic boy whose pain ignited love and awareness in the hearts of those in his presence­—a boy who brought people together across differences and grief to spark change in the world.

“He came down here with a job to do,” Tammi says. “And we’re just trying to keep it up.”

Like Alessi’s brave little soul, Chad galvanized communities during his short time on Earth. And he inspired the world to care about DIPG.

“The Team, The Team, The Team”

Soon after Chad passed away, the Pediatric Brain Tumor Research Initiative officially launched at U‑M. A goal was set: Raise $30 million to establish a center in Chad’s honor. Three lead donations and a series of generous gifts catalyzed the initiative. Ron and Eileen Weiser made a lead gift, along with donations from Wayne and Shelly Jones and the Jones Family Foundation, the Glick family and Alro Steel, and The ChadTough Foundation. William (BBA ’84) and Sharon Stein, Frank (BBA ’61, MBA ’62) and Barbara Westover, and David (BGS ’85) and Joan (AB ’87) Evans also offered their abundant support.

“We wanted Michigan to be really good around pediatric brain tumors and DIPG,” Tammi says. “Of course, when you get Ron Weiser engaged in something, the next thing you know there’s a campaign, and we’ve raised $30 million.”

In 2018, Michigan Medicine and the ChadTough Foundation announced at the foundation’s Champions for Change gala that the U‑M Board of Regents had approved the Chad Carr Pediatric Brain Tumor Center (CC-PBTC). Thousands of supporters from across the country had come together to raise the $30 million needed to establish and name the center in Chad’s memory.

Today, the center is led by Opipari, Muraszko, and Eric Fearon, MD, PhD, the Emanuel N. Maisel Professor of Oncology and Rogel Cancer Center director. It unites experts from multiple specialties and schools across campus, including pediatrics, radiology, neurosurgery, radiation oncology, genetics, cancer metabolism, neuroscience, epigenetics, and pathology, as well as engineering and public health, to accelerate research on DIPG and other pediatric brain tumors. The CC-PBTC’s monthly DIPG and pediatric brain tumor focus group brings together experts from nine labs in eight departments, divisions, and programs at U‑M: Pediatrics, Molecular and Integrative Physiology, Chemical Biology, Radiation-Oncology, Hematology and Oncology, Neurosurgery, Internal Medicine, Pathology, and the Michigan Center for Translational Pathology, as well as visiting expert faculty from other institutions. Funding from a variety of sources, from private donors to the National Institutes of Health (NIH), has since helped transform Michigan Medicine into the preeminent center for pediatric brain cancer research, leveraging the university’s depth and breadth of expertise across disciplines.

Donor support at the CC-PBTC, in particular, has helped increase the scope of DIPG research at U‑M, with 25 scientists working on DIPG projects at the university. Internationally and domestically, collaborations are underway with leading institutions, such as the Institute of Cancer Research in London, the Cincinnati Children’s Hospital, Stanford University, Northwestern University, University of Wisconsin, University of Toronto, University of Bonn, and the German Cancer Research Center (DKFZ), among many others.

For years, U‑M has had a robust pediatric brain cancer research program that has received generous donor support, propelling advancements in Castro and Lowenstein’s work as well as that of many other researchers across campus, including Carl Koschmann, MD, and Sriram Venneti, MD. Support from The ChadTough Foundation enabled Castro and Lowenstein to gather data that allowed them to apply for future grants. Now, the duo are among many at U‑M who are closer than ever to finding a treatment for pediatric brain tumors like DIPG.

The Dynamic Duo

Inside the Castro/Lowenstein Lab, towers of glass beakers line tables and shelves. Among the beakers, petri dishes, and microscopes, you can find the lab’s namesakes hard at work. At U‑M, the couple’s lifelong quest to advance treatment for adult brain cancers is bringing hope to children with malignant brain tumors.

Castro and Lowenstein are remarkable for having developed a pioneering therapeutic approach that uses a never-before-tested combination of genetic and immune therapies. The approach has yet to be implemented in human patients, but it has exciting implications for the future of treatment.

While gene therapy is not a new concept, its human implementation has only recently reached the clinical arena—a milestone that could lead to additional discoveries relevant to the treatment of children with these aggressive brain tumors. It is the first time that a gene therapy immune response will be tested against DIPG.

The innovative treatment approach reprograms the brain’s immune environment to harness the power of effector immune cells to recognize, attack, and kill cancer cells growing in the brain. If the treatment works in mice, the hope is that the treatment can be safely tested in children with DIPG and other high-grade gliomas.

Importantly, this novel approach is expected to position the brain’s immune system as a vital tool against the return of tumors in patients who have already received treatment. The discovery is based on enhanced understanding of how tumors behave, a critical component for developing targeted therapies.

Castro and Lowenstein attribute a great part of their success to the power of philanthropy—from the donors who backed their early research to the ardent supporters whose generous contributions propelled their work to new heights.

“Without philanthropy, this never would’ve happened,” Castro says. “We went from having no resources to work on DIPG to donors funding the work that allowed us to go to the NIH—the final seal of approval that this group at U‑M is doing good work in this space.”

Donors have also provided numerous tools for Castro and Lowenstein’s lab.

“Show her the microscope!” Castro says to Lowenstein as we’re led through a sea of black-top tables, computers, and other high-tech equipment.

In the room stands a donor-funded confocal microscope, which researchers use to study the behavior of tumor cells over time. Lowenstein points to the shades of red, pink, and violet on a computer screen an arm’s length away, where 3D images from the microscope actually show the cancer cells moving inside the living tumor.

The cells they study are donated by patients like Chad.

“You are trying to do science, and science is supposed to be very detached,” Castro said. “But on the other hand, you’re working with people. It’s families giving you money and patients who are donating tissue samples. And sometimes, in the case of Chad Carr, they donate the whole brain. It’s a really big responsibility.”

Castro escorts us into a lab across the hall where large, cylindrical cryogenic freezers hold samples of tumors that were donated postmortem. As we stand a few feet from Chad’s preserved tumor in the Department of Neurosurgery’s Brain Tumor Tissue Bank, the magnitude of his sacrifice is poignant.

The patients and families who have donated tumor tissue have enabled other researchers at U‑M to safely biopsy and sequence the DNA of many DIPG tumors—yielding vital information unavailable to the Carrs when Chad was diagnosed that has since spurred discoveries.

For Tammi, each study that results in a new discovery feels like clearing a major hurdle in the race to discover effective treatments for a tumor as aggressive as DIPG. Castro and Lowenstein are confident that the extensive research underway across U‑M will provide hope and result in discoveries that show great potential for improving outcomes.

For Lowenstein, focusing on the research efforts underway and the promise they hold for the future helps to provide patients and their families with hope.

“The fact that we don’t have a treatment doesn’t mean it doesn’t exist—it means we don’t have it yet. It doesn’t mean it’s impossible,” Lowenstein explains with a confident smile.

Chad’s Legacy

But progress takes time—sometimes more than one has to give. It is a truth that Tammi wrestles with often.

“If someone had done this work 30 years ago, I always think about how maybe Chad would be here,” she says.

More than four years have passed since the Carrs’ lives were forever altered, leaving them to rebuild their family puzzle with its smallest piece missing.

“You’re never the same person; you never will be. It’s never something you get over and move on from; you’re just different,” Tammi says, gazing into the next room at a family portrait with Chad. He would have celebrated his 10th birthday this year.

It’s only with relentless positive energy, perseverance, and an enduring faith that the Carrs have turned tragedy into triumph. And they have no plans to stop now.

“We’re going to be doing what we’re doing—even when we don’t necessarily want to be doing it. We know it’s what we’re meant to do,” Tammi says. “It was Chad’s job, and we’re just continuing it.”

Steady progress toward treating DIPG at Michigan shows no signs of stopping, thanks to expert scientists, a strong community of supporters, and the largest alumni base in the world working to help the Carrs “make this big.” The Michigan team is paving the path to DIPG treatment through powerful collaborations—from every donor and researcher, to every athlete, coach, and alum that supports the effort in ways big and small.

“I’m not saying we believe anything will be solved within the walls of one institution, but they’re collaborating. These are special people,” Tammi says. “We keep waiting for there to be that plateau or that lull, but it has been years and we haven’t hit a plateau.”

Progress continues, and Tammi knows Chad is still at work.

“We’d give anything to have him back and not do any of this, but he had a job to do, and it was a big one,” she said. “We really believe one person can change the world, because Chad’s doing it—and people are jumping in with him.”

With new knowledge, funding, and a potential treatment for DIPG being tested, there is hope that survival rates will increase, representing critical advancements since Chad lost his battle with the disease. While progress won’t bring back their son, Tammi and Jason say that Chad’s legacy has provided a new perspective on life.

“We’re all a really small part of this giant plan that we don’t always understand,” Tammi tells me as we sit on their family room couch, a quilt displaying photos of Chad draped over the cushions. “But we’ve seen the power of hope through this little boy.”

“It has crystalized what’s really important. Your house doesn’t really matter, your job doesn’t really matter, your car—none of those things are that big of a deal,” Jason says.

Maybe Alessi’s Brave Little Soul said it best.

“God replied, ‘Have you not noticed the goodness and love that is the offspring of that suffering? Look at how people come together, drop their differences, and show their love and compassion for those who suffer. All their other motivations disappear, and they become motivated by love alone.’”

Editor’s Note: This article has been edited to correct the spelling of Dr. Karin Muraszko’s name.