“I’d love a vacation,” says Natalie Longino, MD, PhD, with a smile. When she finally gets to a point where she can take one, she will have earned it.
Longino is in the Physician Scientist Training Program at the University of Colorado Division of General Internal Medicine. During her IM residency, she spent a year as a scholar in the CU Department of Medicine’s Colorado StARR Program (Stimulating Access to Research in Residency), which seeks to train outstanding clinician-investigators focused on translational research in heart, lung, and blood disorders. Currently, she is a first-year fellow in the CU Division of Medical Oncology’s Hematology Oncology Fellowship Program, under the direction of CU Cancer Center member Daniel Bowles, MD.
During her time at CU she has worked on numerous issues, sitting on committees addressing academic curricula, residency programs, and even educational website development. And now, she and her husband are raising two small daughters.
“For women who are trying to do this with kids, it’s tough to find a balance,” Longino says. “On the days I feel like a good mom, I feel like a bad scientist or a bad doctor, and vice versa. But I tell myself to stick with it. We need more women as physician-scientists. And I have two little girls who I want to inspire.”
Longino says that as both a doctor and a scientist, “my dream is that you see your patient in clinic and then go to the lab and try to figure out what their specific cancer is doing to better guide treatment designed specifically for them. We are moving in the direction of personalized medicine, and I hope to be a part of it.”
Longino’s interest in medicine began at an early age, growing up in Michigan. “My dad is a maternal fetal medicine doctor, and he does high risk obstetrics. I grew up around medicine and always looked up to my dad. When I went to college, I kept trying to deviate, thinking about art or music. But I kept coming back to science classes and liked those the most. Gosh darn it, Dad was right!”
Her father also encouraged her to consider research. While she was an undergrad studying cellular and molecular biology at the University of Michigan, she was ready when the opportunity to start her research career arose. “I needed a summer job, and a research lab was hiring a lab tech, and I wound up doing more than just tech-ing and simply got hooked on research.”
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Longino enrolled in the Medical Scientist Training Program, a combined MD-PhD track, at the University of Washington.
“I started initially working on ovarian cancer as an undergrad, which got me interested in cancer biology in general,” Longino says. “And then, when I went to UW in 2011, that was the year that the first immune checkpoint inhibitor got approved, the first mainstream immune-based therapy for cancer. Everyone was going crazy about immunotherapy, and I thought, ‘I don’t know anything about the immune system, so I should probably learn.”
She joined the lab of Paul Nghiem, MD, PhD, a specialist in skin cancer whose lab team was studying immune response to Merkel cell carcinoma, a rare, aggressive skin cancer. “While I was there, the lab got an immune checkpoint inhibitor approved for that disease, and I became fascinated with immunobiology of cancer,” she says.
Natalie Longino, MD, PhD, with a patient. Photo courtesy of Natalie Longino.
Longino’s father came to her PhD thesis talk on the immune response against Merkel cell carcinoma. “He told me, ‘A lot of the immune markers that you mentioned in your talk are expressed in the uterus and fetal cells during early pregnancy. Have you looked into that?’ I thought that was intriguing, so I started reading, and it turns out there’s a lot of shared genetic and immunologic mechanisms between the uterine lining during early pregnancy and cancers.”
She says she began exploring the hypothesis that “mechanisms that facilitate a healthy pregnancy and create an immune-tolerant environment that allows a fetus to grow may be co-opted by tumors to also create locally immune-tolerant environments. In my research at CU, I’ve been investigating whether these mechanisms exist in melanoma.”
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In particular, Longino says that “one of the main drivers of that immune-tolerant process is a special type of cell called a decidual natural killer cell, or dNK, which is the most prevalent immune cell in the uterine lining during early pregnancy. These dNK cells have been found in some tumor types, and so I wanted to see if they played a role in melanoma, and sure enough, we’ve found them in there. We still don’t know their significance, but we at least found that they’re there. I plan to spend my fellowship research time exploring their impact on the tumor immune environment.”
In November, Longino was awarded a National Institutes of Health grant to further investigate dNK cells in melanoma and whether their presence or absence corresponds to how the cancer responds to immune therapies. “The dNK cells express specific markers that we could target to inactivate them, so potentially we could convert this immune-tolerant environment into a more reactive one to attack the tumor,” she says.
At CU Anschutz, Longino has worked in the research labs of medical oncology professor William Robinson, MD, PhD, and biomedical informatics professor Paul Norman PhD. She counts them among her many mentors, along with Richard Tobin, PhD, an assistant surgical oncology professor who studies the immunology of melanoma. “Those three have been incredibly supportive and made this project possible,” she says.
In Washington, Longino’s MD-PhD track was nine years long – two years of med school, four years of PhD work, a post-doctoral year and a final two years of med school leading to her MD. That’s typical of such programs, and she says, “the transition from graduate school back to medical school was very difficult for me, at one point I was told that I was ‘too far behind’ to succeed.” That’s why some of her committee work has been aimed at developing curriculum improvements to help students like her make the pivot from their science work back into medical training.
“That’s why, when I came to Colorado, one of the things I asked in the interview was, is there any way we can develop a course for MD-PhDs returning to medical school? And right off the bat they said, ‘Yes, that sounds great, how do we make that happen?’ So in my intern year of residency, together with the CU Medical Science Training Program leadership, we put together a course that aims at improving the transition back to medical school. The course is in its fifth year and it has become a part of the CU MSTP curriculum. It's been really inspiring to me how the faculty at CU care so deeply about improving this process and training physician scientists.”
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It’s now been 14 years since Longino began her academic medicine journey after college. Her advice to others embarking on a similar journey: “Understand that it’s a very long road and there are highs and lows. You won’t enjoy every step but hopefully you enjoy most of it. The important thing is to find people and hobbies to keep you grounded. For example, I like doing home renovation projects. If it feels like I’m struggling in the clinic or the lab then I go home and paint a wall or work in the garden and feel a sense of accomplishment.”
Regarding people, she says her husband “is my rock. We’ve been together since early med school, and he has always been my champion. He says things like, ‘This is tough now, but remember how excited you get in the lab when you do a new experiment or how you feel when you were able to help a patient? Remember those feelings.’”
Photo at top: Natalie Longino, MD, PhD, in the lab. Photo courtesy of Natalie Longino.