Profiles in Cancer Research
Dr. Marcia R. Cruz-Correa
Director, Gastrointestinal Oncology Program, University of Puerto Rico Comprehensive Cancer Center
As you walk down the halls of the new comprehensive cancer center at the University of Puerto Rico (UPR) Medical Sciences Campus in San Juan, keep an eye out. The woman bustling by could be Dr. Marcia Roxana Cruz-Correa, and she’s not someone you want to miss.
“She knows where she’s going, and before you quite realize it, you’re shaking your head with a bemused smile and pretty much wanting to go along with her,” said Dr. Francis Giardiello, gastroenterologist and clinical researcher at the Johns Hopkins School of Medicine and Dr. Cruz-Correa’s clinical mentor. “Marcia is definitely running a 3- or 4-ring circus,” he added.
In addition to clinical and academic research, she is a physician-scientist committed to seeing patients in the clinic. When she was a kid, she said, “My mom tells me that I was prowling around the house looking for things to fix. I like taking care of patients and people, and endoscopy is one way of ‘fixing stuff.’ It’s really satisfying for me.”
She was well-served by the pre-med undergraduate program at UPR, where she also attended medical school. To help pay her way through, Dr. Cruz-Correa joined the U.S. Army Reserve—another ring in the circus.
“I married my high school sweetheart when I was 23, which seemed pretty natural, unless you were in your first year of med school,” she said. “Two years later I got pregnant, so before I was putting Dr. in front of my name I was a mom. Estefania Jordan was born in 1993.
Dr. Marcia Cruz-Correa explains the promise of epigenetics: To better understand genetic mutations that predispose people to cancer so that steps can be taken to modify cancer risk. (Artwork by Jeanne Kelly® 2004)
“But I always knew I wanted to do clinical research, which definitely meant leaving the island. I did my internal medicine residency in Puerto Rico, but since Estefania was no longer a baby, you know, I decided to just go for it.” Fifteen fellowship applications later, toddler and husband in tow, she found herself a first-year fellow in gastroenterology at Hopkins and a Ph.D. student in the Johns Hopkins Bloomberg School of Public Health.
The Baltimore Years
Loss of Gene Imprinting and Cancer Risk
Most genes come in pairs, one inherited from the mother and one from the father. In most cases, both copies, or alleles, of the gene are expressed or “switched on.” But for some genes, only one of the two alleles is expressed. The other is silenced or “switched off” through a process known as “imprinting.” When a normally silenced gene loses its imprinting and is expressed from both alleles, disease can follow.
In humans, the IGF2 gene is normally imprinted, with only the paternal allele expressed. Dr. Feinberg’s lab at the Johns Hopkins University School of Medicine discovered that the normally silenced maternal IGF2 allele can undergo loss of imprinting. IGF2 is a growth promoting gene, and evidence is mounting that individuals with loss of imprinting of IGF2 may be at increased risk for developing several cancers, including colorectal.
Dr. Giardiello became her clinical mentor and referred her to Dr. Andrew P. Feinberg, now the King Fahd Professor of Molecular Medicine and a pioneer in the study of methylation and other epigenetic aspects of cancer. His laboratory had discovered loss of imprinting of the insulin-like growth factor II (IGF2) gene in Wilms tumor and had been doing work to extend the connection to colorectal cancer, which might have bigger clinical implications. (See the sidebar for further explanation.)
“People are familiar with the IGF1 gene for its role in diabetes, but IGF2 has kind of been overlooked,” Dr. Cruz-Correa explained. Overexpression of this gene may help tumors grow, and Dr. Feinberg’s group had found the gene not only in the tumors but also in the normal tissue of patients who developed colorectal cancer. The overexpression of IGF2 is very unusual among the general population and might one day lead to a way of identifying those at higher risk for developing the disease.
Dr. Cruz-Correa worked with Dr. Feinberg’s team on designing a clinical study to learn how common loss of imprinting of IGF2 might be. She persuaded the private practice physicians affiliated with Hopkins to join her network and provide a ready stream of colonoscopy patients. But she also had to convince the patients to join the trial, and historically fewer than 4 percent of cancer patients do so.
“Practically none of these patients refused to join,” recollected Dr. Giardiello. “I think she recruited about 390 out of 400 patients she approached. She is unique, a special person,” he explained. “If she wants your help, she makes it almost irresistible with her sincerity and her personal appeal to bring you along. That’s her special quality.”
As Dr. Feinberg puts it, “Preserving the sense of wonder and joy in discovery is one of the keys to succeeding in science or medicine. It is most unusual to find people like Marcia; she has that quality and she brings it to the laboratory, the public health arena, and also to the one-on-one experience with her clinical patients. It makes her a most extraordinary exemplar of what we aim for in translational investigators.”
After finishing her fellowship, Dr. Cruz-Correa has continued her connection with Hopkins as a visiting associate professor of medicine and has been the lead author on several studies coming from the Feinberg lab.
Navigating the Landscape of Opportunity
Like most successful researchers, Dr. Cruz-Correa has learned how to navigate the landscape of programs and opportunities at NIH. She received K07 and K22 awards from NCI, and with her R03 grant she helped to develop the first Familial Colorectal Cancer Registry in Puerto Rico. (As patients diagnosed with colorectal cancer join this group, investigators gather important information on their medical history, diet, and other lifestyle factors that may have contributed to their cancer.)
The UPR hospital she bustles through would not exist without the help of NCI and the Center to Reduce Cancer Health Disparities. The U-54 Minority Institution/Cancer Center Partnership program (MI/CCP) helped the UPR Medical School to develop a comprehensive cancer center by establishing a working relationship with the University of Texas M.D. Anderson Cancer Center in Houston, where Dr. Cruz-Correa remains an adjunct associate professor of surgical oncology.
“When we got the planning grant in 2002,” she said, “we went from having no building and a few investigators to this beautiful facility with state-of-the-art laboratory facilities and more than 60,000 square feet of bench space. We’re still recruiting, but our faculty is already at 14 or 15, each one of us with our own team of people. So it’s growing, and it shows what federal support can accomplish.”
Biomedical research isn’t for the faint hearted, she believes. “Sometimes the most difficult thing is to get people to believe in themselves. Then you need to know what opportunities exist. I am so grateful to NCI. Over the years I’ve worked with many people at NIH, and they are unfailingly eager to provide good advice, nurture hope, and really often inspire people. I’m their biggest fan.”
“Pass it Forward”
Dr. Cruz-Correa thinks that more minority women can and should join the ranks of cancer researchers. There are disparities, she admits, but she believes that “this is a field for anyone who has the desire, the energy, and the passion. The help I’ve gotten, I want to pass it forward, and I consider mentoring a privilege. Of course we all work very hard. But anyone who is willing to do that, and wants advice, I’m delighted to help them. What matters isn’t your background, it’s your attitude.” Although she serves just 2 weeks of active duty each summer, her own attitude, energy, and passion have taken her to the rank of lieutenant colonel in the U.S. Army Reserve.
Certainly her most treasured mentoring project is Estefania, who has been attending conferences and meetings with her recently. At the age of 16, Estefania says that she wants to become a doctor, like her mom. “I wanted her to know her mom was more than just the person she saw at home. That often when I’m away, it’s because I’m at the clinic helping other people,” said Dr. Cruz-Correa. “She sees her mom as a speaker and active part of this cancer research world.”