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During her medical residency in pediatrics at Staten Island University Hospital, Joanna Pierro, DO, was increasingly drawn to the science of pediatric leukemia, and the prospect of developing clinical interventions that might cure even her sickest patients. Dr. Pierro, now a fellow in the at ������� Langone Health, found the opportunity to pursue her interests in the lab of William L. Carroll, MD, the Julie and Edward J. Minskoff Professor of Pediatrics and professor in the .

The fellowship’s 3-year program emphasizes both clinical and research training in cancer and blood disorders.

Dr. Pierro was attracted to the personalized approach to patient care at the Stephen D. Hassenfeld Children’s Center for Cancer and Blood Disorders, and to the opportunity to conduct research with Dr. Carroll, a world-renowned expert in pediatric leukemia who has authored more than 200 journal publications.

As a clinician with no formal experience in basic research, though, Dr. Pierro needed to adjust to the “completely foreign” setting of Dr. Carroll’s lab. “For me, this is a brand-new, exciting world,” she says.

Over the past few decades, doctors have made big strides in treating acute lymphoblastic leukemia, or ALL, which is the most prevalent childhood cancer in the United States. Roughly 90 percent of the more than 3,000 patients diagnosed annually with ALL can now be cured.

“Unfortunately, we have not seen the same improvement for patients who relapse,” Dr. Pierro says. In Dr. Carroll’s lab, she is scrutinizing the second most common leukemia-associated genetic mutation seen at relapse. The gene, called MMSET, has been implicated in drug resistance in other cancers, hinting at a similar role in ALL. “It would be a prime target for therapy if we were able to find the underlying mechanism by which it either imparts drug resistance or initiates relapse,” Dr. Pierro says.

As part of her project, she created three pediatric leukemia cell lines containing, respectively, a normal, overactive, and mutated form of the MMSET gene. After exposing the lab-grown cells to drugs used to treat ALL, her experiments suggest that the gene mutation doesn’t play a direct role in drug resistance. Instead, she and Dr. Carroll hypothesize that the mutation may physically alter the genome and change the activity levels of other genes in ways that allow leukemia cells to persist and resist chemotherapy. So far, her work has shown that the MMSET mutation may indeed spur multiple physical changes to other parts of the genome.

For Dr. Pierro, embarking on such a complex investigation as a rookie in bench research was a daunting undertaking.

“Like all diagnosticians, my instinct is to figure out what’s wrong, fix it, and move on,” Dr. Pierro says. “In the lab, it’s a very different process.”

Dr. Carroll, for his part, immediately recognized the potential of his “energetic and poised” research fellow. “Joanna just jumped right in,” he says. After he helped her to script the project’s outline and to brainstorm methods, Dr. Carroll says, she deftly filled in the blanks. In less than two years, he explains, Dr. Pierro has enthusiastically shifted gears to conduct complicated lab experiments in addition to her clinical duties, generated an “enormous” amount of data, and been awarded two grants from private foundations. By clarifying how a mutation may help ALL resist chemotherapy and return in children who were seemingly in remission, he says, her data could help inform new clinical strategies. “She’s a poster child for taking lab work and ultimately bringing it back to the clinic,” Dr. Carroll says.

From troubleshooting and offering advice on experiments to helping her secure funding and contacts in the research and clinical worlds, Dr. Pierro says, Dr. Carroll’s strong advocacy for her career goals and his commitment to leukemia research have fueled her success.

“Because he’s so passionate about what he does, it’s very easy to become passionate about it, as well,” she says. “His excitement and his drive have really pushed me to want to be even more successful.”

After gaining additional research experience in Dr. Carroll’s lab, Dr. Pierro hopes to remain in academia and join the ranks of physician–scientists who undertake both clinical and research projects. “Stepping out of my comfort zone and training with Dr. Carroll has prepared me to pursue translational research projects and serve as a bridge between basic scientists and clinicians,” says Dr. Pierro. “The perspective I’ve gained from my basic science colleagues has been invaluable and given me a broader appreciation for all the amazing things yet to be discovered.”

The Meaning of Mentorship

Mentors can introduce young investigators to the thrill of scientific insight and provide a compass and map to point them in the right direction. “Young investigators make a major investment in us,” says Dr. William Carroll, “and of course we need to reciprocate and make a major investment in them to ensure their success.” When recruiting aspiring researchers to join his lab, Dr. Carroll looks for motivated and hardworking individuals who press on despite the inevitable setbacks, often taking the work in new directions in the process. Stumbles along the way, Dr. Carroll says, become a shared responsibility between mentor and mentee and an opportunity for growth. Weekly lab meetings, meanwhile, can serve as think tanks to share, discuss, and build on challenges and successes alike.