Scientific nomads in search for a cure for brain tumors
ANN ARBOR– After moving to Washington, D.C., from her native Argentina, María Castro was feeling lonely.
The post-doctoral fellow with the National Institutes for Health would hear about her co-workers’ plans for the weekend while she stayed behind alone. She didn’t know anyone in the country and had no contact information for the only fellow Argentinian she knew about, a Pedro Lowenstein, whom a friend had told her about before leaving Buenos Aires.
“My friend had said he was nice, but I didn’t have a phone number or anything. My roommate said just leave it to me,” she said “A week later she comes in with his office number, all the information, and she says ‘Call him.’”
A month later, she would give in and make the call.
“And that’s when I made the biggest mistake of my life,” Lowenstein says, interrupting the story Castro had been telling, a mischievous laugh predicting an upcoming joke.
Simultaneously, she says, “He picked up the phone,” as he says “I picked up the phone.” They both burst into laughter.
The phone call would mark the beginning of a long-term friendship and professional partnership that would lead the couple to marry, work in some of the most prestigious research organizations in Europe and the U.S. before being recruited five years ago to set up the Castro-Lowenstein Laboratory at the University of Michigan, where they conduct ground-breaking cancer research.
Sitting in her office, Castro talked about the work that’s consumed most of their lives since that call in 1986. Printed materials are piled up on every inch of available surface. The bookshelves are piled to the ceiling with medical journals, and the walls are covered with research printouts. Next door, the walls of Lowenstein’s office are decorated with DNA sequencing posters, and the bookshelves are filled with research on genetics — his latest research interest.
The offices are part of the Castro-Lowenstein lab that includes three offices and five laboratories rooms, occupying a triangle corner of the fourth floor of the Medical Science Research Building III, part of a maze-like research structure at U-M’s medical campus.
Castro says they focus on malignant brain tumors, including those that grow on the brain stems of children.
“You can’t surgically remove them, you can’t irradiate them, chemotherapy doesn’t work on them. It’s a death sentence. Children live six to 12 months. So we’re working very intensely in this type of tumor.”
“Sometimes people ask me, why do you work on weekends?” adds Lowenstein. “I tell them: Look, patients don’t have weekends. Once you know a patient, it mobilizes you. They really need treatment.”
The long journey from Argentina to the U-M
The daughter of immigrants who fled Spain amid the civil war, María Castro grew up in Lomas de Zamora, about 12 miles (19 kms.) from Argentina’s capital of Buenos Aires.
Her father was an engineer, and her mother returned to school to become a pharmacist while raising the family of two daughters and a son.
“She would pay me to let her study. That’s how I would make money when I was 6 and 7 years-old,” Castro said. “She would study organic chemistry, and I would think the drawings on her books were bee hives.”
Her younger sister, also a scientist and artist, died recently of lung cancer. Her brother is an architect in Cordoba, Argentina.
Castro was attending Universidad Nacional de la Plata in Buenos Aires, when the “Dirty War” erupted in Argentina. During the political upheaval from 1974 to about 1983, the military, security forces and right-wing death squads hunted down, disappeared and killed political dissidents, student activists, labor union members left-wing guerrillas and anyone else suspected of being a socialist.
“Things got really bad in 1976, when the repression started and students were a prime target. The army would enter the classroom, yell, ‘On the ground,’ and they would randomly pick some of them, who never again turned up.”
Disappearances were common. The commuter train she used would randomly be stopped in the middle of nowhere. Some people would be arrested, and the train turned around. As she walked the rest of the way home, her parents would wonder if they would see her again. Her own brother was kidnapped and tortured.
“When you’re living under those circumstances, you go on autopilot. You don’t think about the magnitude of what’s happening. You go into survival mode, I think, that’s the defense mechanism we all have,” she said.
Despite the challenges, Castro would graduate with honors from chemistry and obtain master’s degrees in biochemistry and education technology and a doctorate in biochemistry.
Upon graduating, she had the opportunity to join the National Institutes of Health as a fellow with the National Institute of Child Health and Human Development. While she had a job waiting for her in Argentina and her parents expected her back, she really didn’t plan to return.
“For my parents, the plan was that I would go to train in the USA for three years and come back to Argentina. But I didn’t think I wanted to come back. For many years, I was in rough shape. I couldn’t come back,” said Castro, who years later in England would be treated for PTSD.
For Lowenstein, the years of the Dirty War were also difficult, and in a way would push him toward medicine and research.
The sole child of Holocaust survivors, Lowenstein grew up in Buenos Aires in a German-speaking household surrounded by stories of how both sides of his family had survived the horrors of anti-Semitic policies and war.
His paternal grandfather had emigrated from Germany to Argentina around 1936, intending to protect the family from rising xenophobia in Europe. His maternal grandfather, thinking he would be protected because he had served in the military, would stay, paying a hefty price. Lowenstein’s mother would lose both parents in Nazi concentration camps and emigrate initially to England and later to Argentina before meeting and marrying Lowenstein’s dad.
While his father would not speak about their ordeal in Germany often, his mother would never stop talking about it, he remembered.
“My dad recovered, moved to Argentina, got along with the locals and embraced the Argentinean culture and way of life. My mom never recovered, never got used to Argentina. Psychologically, my mother never left Germany,” he said.
At home, she would make him eat for all the people they had lost their lives in concentration camps during the Holocaust, he said. And because the family only spoke German at home, he would have to learn Spanish when he started attending school.
After high school, he had to complete a one-year mandatory military service as the dictatorship took hold in Argentina and as he started attending Universidad de Buenos Aires. He wanted to study psychology, and really enjoyed philosophy and literature, but the military had closed those schools, so at his mother’s suggestion he enrolled in medical school instead.
“Those times were very difficult because we went from being, you know, a normal country to it becoming a paranoid society place. If you were caught without identification papers, without ID, they could take you and make you disappear,” he said adding people grew weary and jumpy, not knowing who would be next.
“Even now, when I see a police car, my blood pressure goes through the roof. My son noticed once, told me, ‘Dad, it’s just the police’. And I was like ‘exactly’”.
During that first year, Lowenstein said he and a friend decided to research a topic they knew nothing about – something easily achievable then, he concedes – and started studying the pineal gland, a small gland located in the brain that helps regulate hormones.
For their research they talked to Daniel P. Cardinali, who specialized in this area and kept going back for more information until the researcher offered them an opportunity to do research with him.
“We were just so proud to start doing research. I fell in love with it,” says Lowenstein, adding that with several years of research under his belt, and after obtaining his doctorate in medicine with a dissertation focusing on the pineal gland – he received a post-doctoral fellowship at the Johns Hopkins University School of Medicine.
Later, Lowenstein would accept a research scientist position Oxford University, in England, where Castro would join him after obtaining a position at the University of Reading. Three years later, they moved to the University of Dundee in Scotland, where their son Elías was born. Next, they went to University of Manchester in England before returning to the U.S. to work at Cedars Sinai Medical Center/UCLA, settling in California so Elías could finish high school there. He’s currently studying neuroscience at Berlin Charite Hospital in Germany.
In 2011, University of Michigan convinced them to move their lab to Ann Arbor.
Asked if they’re sticking around Ann Arbor, Lowenstein jokes.
“Well, if you look at our history you can tell we can’t answer that question,” he teases as María answers in a serious voice, giving him a reproachful glance.
“We’re very happy at the University of Michigan. It’s excellent with all the facilities for our work and an excellent and very supportive department of neurosurgery. We already have started the clinical trials. We’re here for a while.”
Hers and his lab
This year, Castro became the first U-M researcher to receive the prestigious Javits Neuroscience Investigator Award from the NIH. She will receive $2.3 million for up to seven years to continue her work in the treatment of brain cancers by discovering the cellular, molecular, and immunological mechanisms, that mediated tumor progression, and introducing genetic changes into tumor cells to prevent cancer invasion.
In her most recent publication, Castro and her team explain how they developed a brain tumor model in mice that could help treat children with malignant brain cancer.
While each has different focus on their work, Castro and Lowenstein said their partnership has benefited them both professionally.
“Each one of us has an independent line of research, but we collaborate a lot. Pedro with his background in medicine and I with my background in biochemistry, we have complementary strengths… We help each other but we have our own projects. I am really interested in personalized medicine and how through tumors’ genetics you might adapt treatments so they work better in determined tumors. That’s why I study a lot of molecular biology, biochemistry, animal modeling,” Castro said.
Lowenstein added, “And right now I’m more focused on problems like the immune system and how the different branches of the immune system –the adaptive and the innate immune system– can be used to attack a tumor. Everything we’ve done and that is in clinical trials is trying to do cellular and biological engineering and now we’re starting to exploit the innate immune system to attack tumors.”
“The fact that María and I have been able to convert what we’re doing in labs into clinical trials is very gratifying and moving. Having met many people who die of this terrible illness… they really need a new treatment.”
While they recognize that unplugging from work can be difficult — they work long hours and many weekends — working together has its advantages.
Do you fight a lot?
“Nooo,” Lowenstein jokes.
“Well, yes, but in our work that’s an advantage,” Castro says. “Because in our job we have to be very critical and if you’re not very close to someone you’re not going to criticize, a colleague for example, because you’re afraid to offend them. But between us there’s none of that. I think that’s why we push each other, we criticize each other because we want the other one to do his/her best. That has it’s pros and cons. But for work it’s really positive. We help each other a lot.”
“We’ve spent many years working together. We like to do the same things, and we like to talk about this and that,” he said. “Working together was never a problem and when Elías was young we understood if the other one had to be working,” he said, admitting he’s never been sorry for picking up the phone back in 1986.
Neither was Castro.
“So he answered the phone and said: ‘Look, I have friends in Washington and I’m coming for a birthday party over the weekend. How about we go out?’ “And I asked him ‘And how do I recognize you?’ He says I have a yellow Toyota,” she recalls, as both start laughing again. “Sure enough he comes and the car… you can see it from blocks away. It’s yellow yellow, egg yolk yellow.
“And that was that. That’s how we met and how we became scientific nomads in search of a cure for malignant brain tumors.”