Translating Science Into Medicine
Basic scientist Donald Vander Griend, PhD'05, and clinician Russell Szmulewitz, MD'03, investigate new strategies for preventing and treating prostate cancer
In his sixth floor laboratory, Donald Vander Griend, PhD, studies the development of the prostate and how stem cell genes involved in development impact the initiation of prostate cancer, a disease that affects one in six American men.
Sharing his lab space is Russell Szmulewitz, MD, who sees patients every day whose cancer has spread. His research focuses on the process by which prostate cancer spreads and evolves to become castration resistant.
Together, Vander Griend and Szmulewitz are on a mission to develop new strategies for treating advanced disease. They are using a cell imaging technology called flow cytometry to isolate and study circulating tumor cells as a way to predict if a therapy is working.
"Russ and I have a very symbiotic translational relationship," said Vander Griend, assistant professor of surgery and director of urological stem cell research. "His firsthand experiences in the clinic guide us toward research experiments that are most likely to benefit a patient in the long term. We function so well as a team because he provides the clinical know-how."
Their research partnership is an example of the team science approach to cancer research at UChicago Medicine. Rather than a single researcher chipping away at a problem, a group of individuals with diverse scientific backgrounds working synergistically is thought to make a faster and larger impact on complex diseases such as cancer.
Vander Griend not only has made it his life's work to illuminate the culprit behind prostate cancer, but he has a strong commitment to training the next generation of scientists. The roots of his dedication go back to the research experiences he had at a young age.
As an undergraduate in Grand Rapids, Michigan, Vander Griend was interested in science and medicine, but he did not see himself going to medical school. Research, however, fit with the way his mind worked. Around that time, UChicago had just started its graduate program in cancer biology. In 1998, Vander Griend joined its second class. "That was a really neat program because it was a good middle ground for doing science and helping people," he said. His interest in cancer research was sparked by an internship experience the summer after his junior year of college. He worked in the lab of UChicago Medicine prostate cancer expert Walter M. Stadler, MD.
"I loved it," Vander Griend said. "It was a great environment for me to grow in."
In those days, Stadler, who is now the Fred C. Buffett Professor of Medicine and Surgery, chief of hematology/oncology, associate dean for clinical research, and director of the genitourinary program, frequently collaborated with Carrie Rinker-Schaeffer, PhD, now professor of surgery, medicine, and obstetrics and gynecology, who worked on metastasis and prostate cancer. The two served as early mentors for the budding scientist and wrote letters that helped him get into graduate school.
Vander Griend plunged into his PhD training with piqued curiosity. Under Rinker-Schaeffer's mentorship, he studied prostate cancer metastasis and, for the first time, had the opportunity to watch surgeries and interact with patients. "This was a great way to get my hands dirty in translational research," he said. He knew then that he wanted to stay focused on prostate cancer, a real and common problem that demanded a solution.
A defining moment came at the end of his graduate education career, when he was awarded the Charles B. Huggins Lectureship. For this, he was required to present eight lectures to a general audience. He chose the title "Everything You Need to Know About Prostate Cancer."
Many of the men who attended the lectures interrupted with their own stories, and Vander Griend reminded them he was not a doctor giving medical advice, but rather summarizing the latest statistics. "That forced me to learn everything I needed to learn about prostate cancer and explain it to people who were facing the disease," he said.
The next stop along his journey as a scientist was a postdoctoral fellowship. From 2005 to 2009, Vander Griend trained with a large team of scientists from various disciplines at Johns Hopkins University in Baltimore. His mentor, John T. Isaacs, PhD, professor of oncology, is one of the foremost leaders of the field.
Coming full circle
In 2009, Vander Griend returned to Chicago and his alma mater as an assistant professor. He received a warm welcome from his former mentor, Rinker-Schaeffer, who offered him some of her lab space. He marvels that his career has had many "full circle" moments. For one, he now teaches classes he used to take.
In this next phase of his career, he forged a name for himself as a go-to basic scientist in prostate cancer at UChicago Medicine and is leading many studies on the stem cells involved in prostate development and their potential links to cancer initiation. One of his recent studies showed that an embryonic stem cell regulator called Sox2 plays a different role in prostate cells than in stem cells. His lab found that Sox2 is critical for the growth cells that emerge after hormone therapy. These findings could reveal new research paths in the search for prostate cancer treatments.
Little did Vander Griend know that his chosen field of study would become very personal when two family members were diagnosed. In 2008, his father-in-law developed a rare form of prostate cancer called ductal cancer. Vander Griend asked a well-respected pathologist at Johns Hopkins to analyze the case, and he identified it as an even rarer subtype. This changed the course of treatment because that specific cancer was not particularly aggressive. His 60-year-old father-in-law was operated on at UChicago Medicine by Arieh L. Shalhav, MD, professor of surgery, chief of urology and director of minimally invasive urology. Then, in 2011, Vander Griend's father was diagnosed with prostate cancer and also opted for surgery. Throughout both ordeals, they turned to the expert in the family for guidance.
"I didn't want to tell them what to do, but I gave them the most pertinent materials so they could make informed decisions," he said. Both men are doing well, but it was still hard to watch his loved ones go through major surgery, with its side effects. The experience added a personal perspective to his career and caused him to think more about prevention.
"If there are some simple interventions we can devise to keep cancer from starting and even delay cancer for 10 to 15 years, that will have a significant impact on the population," he said.
Thus, one direction of his research is to figure out how the prostate normally works and how cancer initiates so that one can intervene in the process.
"All the genes we're interested in are good treatment targets in advanced cancer and also seem to have a role in cancer initiation," he said.
Training the next generation
When Vander Griend took on two graduate students in his lab, he transitioned from the mentee to the mentor. The students relied on Vander Griend's guidance at first, but, now in their fifth year, they have matured into productive scientists and drive their own research projects.
Vander Griend often remembers how much one summer in Stadler's research lab shaped his career. Because of this experience, he is enthusiastic about any opportunity to inspire those who are interested in entering cancer research. In addition to training graduate students, Vander Griend has hosted high school students in his lab to expose them to research. He spends as much hands-on time as he can afford mentoring and interacting with his students.
"Fundamentally, the reason why I'm in academia and not industry is because I like training and teaching," he said. "Also, I believe the most productive labs are the ones where people learn the most."
UChicago Medicine has a rich and storied tradition of breakthroughs in urologic cancer, notably the Nobel Prize-winning research of the late Charles B. Huggins, MD, that led to the discovery of hormonal therapy for prostate cancer. Today, physicians and researchers like Szmulewitz and Vander Griend carry on that tradition of high-quality investigation of prostate cancer in search of improved treatment for patients.
As a basic scientist, Vander Griend conducts many of his studies on animal models, while Szmulewitz, assistant professor of medicine, uses clinical trials to test new therapies on patients. Together, their work represents the full spectrum of bench-to-bedside translational research. One of their highest priorities is to further their research on circulating tumor cells (CTCs).
"Prostate cancer spreads mostly to the bones, making it very difficult to obtain tumor tissue to figure out what treatments the person needs," said Vander Griend. "We are taking the patient's blood to isolate cancer cells and analyzing their protein and genetic profile in order to personalize the therapeutics based on the person's biology."
Szmulewitz's lab has developed a novel method of studying CTCs that involves flow cytometry equipment capable of sorting and analyzing the cells in one step.
The translational impact of this work is promising. Patients with advanced disease have more of these CTCs in their blood, and Szmulewitz can use them as clues for how to approach treatment.
For now, CTCs are primarily being used as a research tool, but they could one day be used regularly by clinicians. Vander Griend's lab uses CTCs to test the clinical relevancy of their experiments, and Szmulewitz is leading a U.S. Department of Defense-sponsored clinical trial that incorporates CTCs.
Vander Griend said, "CTCs are a good example of the team science approach that is laying the groundwork for improved therapeutics and prevention strategies for patients with prostate cancer."
Facing funding challenges
Important discoveries are being made every day at UChicago Medicine, but taking those and moving them into patient treatment isn't easy. One obstacle to progress is a lack of funding, the lifeblood that sustains research and a scientist's career.
"I have a ton of ideas and we're always coming up with more, but most of our decisions are based on what's sustainable and what's going to lead to patient impact," said Vander Griend.
Last fall's government shutdown and budget sequester only exacerbated the competition for federal funds. On average, Vander Griend spends 10 to 15 hours a week writing grant applications, which he could have spent reading the literature, training scientists, writing papers and running experiments. "With only the top 10 percent of submitted grants being funded, you have to spend a lot of time on grants."
Vander Griend recently received a research project grant (R01) from the National Institutes of Health. For a total of $1.6 million over five years, he will be able to further study Sox2.
However, he worries about the long-term impact of the funding climate because fewer people are staying in science and choosing to be educated as scientists.
"It's a fun time to be a scientist -- there are so many new technologies that are coming down the pipeline," he said. "Science can move ahead so fast and then there's this roadblock of funding, which is frustrating."
As a result, many scientists rely on donor support now more than ever. Philanthropic dollars can bolster experiments that improve a grant's chances of being funded by the National Institutes of Health. The preliminary body of research that helped Vander Griend garner major federal support was made possible by seed funding from generous benefactors The Alvin H. Baum Family Fund, the late John R. Stanek, the University of Chicago Cancer Research Foundation Women's Board and others.
Szmulewitz also relies on philanthropy to support his bench-to-bedside research. Early-stage projects such as Szmulewitz's CTC work are kept sustainable by a handful of donors, including some of his patients with advanced prostate cancer. Vander Griend and Szmulewitz pool their philanthropic funds to keep their collaborative research alive.
Another challenge of translating basic science to clinical application is the lack of business know-how. Both researchers have established a relationship with UChicago's Center for Technology Development and Ventures, a group that works closely with investigators to build bridges from research to practical applications. For prostate cancer, that could mean the development of a new biomarker that predicts which cases are aggressive and which are indolent. However, testing a biomarker requires enormous sample sets, a kit that works the same way wherever it is used, and product development. Or, a molecular pathway could show promise as a therapeutic target in the lab, but rigorous testing through clinical trials is still needed to evaluate the target and design effective ways of delivering the therapy.
Vander Griend said, "The key to successful translation is confidence that the drug or biomarker is going to make a difference in helping people."
Helping others to succeed in science
Science wasn't always an interest for Edwin Reyes. Growing up in California, Reyes was surrounded by poverty, gangs and low graduation rates. But his parents, political asylees from El Salvador, steered him out of trouble and emphasized the importance of education.
After graduating from community and state college, Reyes returned to his community and taught high school biology for two years. "I want to be an example for students with my background," said Reyes.
He is now a fifth-year graduate student in the Committee on Immunology and pursuing his thesis research in prostate cancer in the lab of Donald Vander Griend, PhD'05, assistant professor of surgery. Reyes' research focuses on the putative cancer stem cell marker CD133 and its role in cell proliferation.
"Edwin is learning how to fundamentally be a scientist, so he can pick an area to study and excel in it," Vander Griend said. After graduation, Reyes plans to pursue a postdoctoral fellowship in cancer immunology and eventually run his own lab.
Meanwhile, Reyes feels grateful for the opportunities he's been given. "If it weren't for federally funded programs geared toward helping minorities in sciences, I wouldn't be here," he said. He is involved in several organizations that help underrepresented minorities succeed in science. Last year, he was an invited panel speaker at the Ivy League Plus program in San Juan, Puerto Rico, encouraging students to pursue graduate education at UChicago.
"I want to let people know it will be okay, even if you struggle," he said. "When I was going through college, it was really encouraging to see other minority students who were getting graduate degrees. Because where we come from, we're the first in our family. When somebody says, 'Look, I'm here, and I'm doing it,' that gives you hope."
This story originally ran in the Spring 2014 issue of Medicine on the Midway, a publication of the University of Chicago Medicine and Biological Sciences Division.
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