Dr. Tasian, an Associate Professor of Pediatrics at the University of Pennsylvania School of Medicine and Chief of the Hematologic Malignancies Program and the Joshua Kahan Endowed Chair in Pediatric Leukemia Research at the Children’s Hospital of Philadelphia (CHOP), discusses the path that took her to the best job in the world, silver linings along the way, and how unexpected lessons from patients can shape the future of medicine.
Where did you grow up and when did you know you were interested in medicine? I spent most of my childhood in Houston, Texas. I decided around the age of 11 that I wanted to be a doctor, and I knew from an early age that I wanted to work in pediatrics. My mother was a teacher and head of a school, so all my summer jobs somehow involved working with children. In high school, I had a deep interest in science, which coalesced with my joy in working with children into the idea of pediatric medicine. During my first year of medical school, I was absolutely fascinated by oncology and thought this was a perfect marriage of scientific investigation and personally meaningful clinical medicine.
What led you to specialize in pediatric hematologic oncology? The pediatrics aspect came from my upbringing being proximal to schools and children. I coached children on the summer league swim team and volunteered at camps. My worst summer job was selling scratchy plaid Catholic school uniforms. During my undergraduate education at the University of Notre Dame, I returned home to Houston to work in a neonatology basic science research lab at the Baylor College of Medicine. There, I had my first taste of doing pediatric-specific biomedical research, and it was exciting and impactful.
The oncology aspect came from recognizing all the opportunities for life-long scientific learning. During my training, I also saw how career paths in oncology could unfold in many ways. The ability to do research that could translate scientific discoveries into better clinical treatments for patients with life-threatening diseases quickly became a critical goal for me as I embarked upon my own career development.
I was fortunate to receive outstanding training in primary care during my pediatrics residency at Seattle Children’s Hospital, although my interest was always in subspecialty care in hematology-oncology. We have incredible relationships with our patients that are deep and long. In pediatric oncology, we end up doing a lot of primary care for our patients along the way, and I remain so grateful for my Seattle training now as a subspecialist. I was so lucky to further that mentality during my pediatric hematology-oncology fellowship training at the University of California, San Francisco (UCSF), when I finally reached my long-set goal of becoming a pediatric oncologist.
Was there a particular mentor or group of mentors who shaped your career path? I was incredibly lucky to have amazing female physician-scientist mentors early in my career. I met one of them when I took a year out of medical school to work in a research lab at the National Institutes of Health (NIH)/National Cancer Institute in the Pediatric Oncology Branch through the Howard Hughes Medical Institute NIH Research Scholars program. During 2001 and 2002, I worked in the laboratory of Crystal Mackall, MD, who was relatively early in her own career at that time. I was amazed at her ability to care for patients with multiple-relapsed cancers on phase I clinical trials at the NIH while running a busy basic science research laboratory. Crystal and I have stayed in touch for over 20 years and have collaborated during the past several years via shared research pursuits. It has been so exciting to see her tremendous career trajectory and continued role modeling as a world-renowned cancer immunotherapist. She is now the Director of the Cancer Immunotherapy Program at Stanford University. She continues to be a wonderful mentor, scientific colleague, and friend.
Another truly impactful mentor is Mignon Loh, MD, who was my postdoctoral research fellowship mentor in pediatric hematology-oncology at UCSF. She is now the Division Chief at Seattle Children’s Hospital and an internationally recognized expert in childhood leukemias. I first met Dr. Loh in 2006 when I was a pediatrics resident interviewing for fellowship. I thought immediately, “This is absolutely with whom I want to work and to be my mentor if I come here!”
This was a case of clouds having silver linings. I decided to go to UCSF for my fellowship because my then-boyfriend/fiancé—now husband—was training at UCSF for his urology residency. After being apart for many years during our training, amongst several time zones and two countries, we wanted to be in the same city. I might not have chosen UCSF had it not been for our personal circumstances, but I truly think it was the best thing that ever happened to me in my career, particularly in terms of joining Dr. Loh’s lab. Now, 15-plus years later, Mignon remains my “forever mentor.” She is a clinical research collaborator in her role as the Children’s Oncology Group ALL Committee chair, a laboratory collaborator in several childhood leukemia research projects, and a close and trusted friend. In reflecting back upon these formative early years when I was young and just starting out, it is amazing to realize the longevity of these and other career mentors and life mentors. I have never forgotten the power of this gift and their investment in me.
You use an approach in your research program that has been described as bench-to-bedside, and bedside-back-to-bench. Can you speak about that phrase and how it informs your work? I have always been interested in late-stage translational research, doing research at the bench with patient samples in our quest to unravel high-risk leukemia biology and discover how to disrupt it. The clinical medicine that I do and the care of children with high-risk leukemias and lymphomas is tied intimately to my research program in the laboratory and in early-phase clinical trials. In all these domains, we are trying to discover the Achilles heels of high-risk childhood leukemias and learn new ways of attacking these heels with targeted therapies.
The children who have a higher risk of relapse with conventional therapies—but we do not yet understand why—are the ones who especially inspire our work in the lab. We are quite fortunate to have access to primary patient samples that are invaluable resources for our studies in the lab. We are so grateful to the children and their families for donating their cells and participating in research.
It is tremendously important to advance promising precision medicine treatments identified in the research lab to children as quickly as possible. What inspires me most about the environment at CHOP is that it is not just about making scientific discoveries in the laboratory, it is about translating those advances to the clinic and turning knowledge gained into new therapeutic opportunities for children.
Patients treated with new therapies in early-phase clinical trials teach us lessons that we never could have predicted from test tubes, cell lines, or mice. Being able to study blood and bone marrow samples from children with high-risk leukemias back in the lab via bedside-back-to-bench studies helps us to further fine-tune our biologic and therapeutic understanding.
What are you working on right now? We remain most excited about and focused upon conquering challenges in “boutique” high-risk genetic subtypes of leukemia in children. As clinicians, we have been lucky to cure many patients with B-cell acute lymphoblastic leukemia (B-ALL) with conventional chemotherapy. However, for those who do not achieve remission and those who relapse, some of the most exciting advances right now are in immunotherapies.
We have also been working diligently for over a decade on the problem of acute myeloid leukemia (AML), which is not nearly as curable in children with conventional chemotherapies. Overcoming chemotherapy resistance with new precision medicine strategies is one of the biggest problems that we are studying in both the laboratory and the clinical trial domain. Developing successful targeted inhibitors or antibody-based or cellular immunotherapies has been much more difficult in the AML space. We are probably five to seven years behind where we would love to be based upon the inspiring successes that we have witnessed in pediatric B-ALL.
How have you seen treatment for pediatric ALL and AML evolve? I am humbled by the ability of pediatric oncologists to connect generously and share knowledge regarding research discoveries to help patients find the right treatment or clinical trial. Most of us practice at academic institutions and are extremely collaborative by nature. The focus on team science within pediatric oncology is incredibly powerful, and I truly believe that is in part how we have made so many advances nationally and internationally.
Children who were diagnosed with ALL or AML in the 1960s or early 1970s had a survival rate close to zero. It is through pediatric oncology consortia-based clinical trials that we have been able to advance cure rates to upward of 85% to 90% for children with ALL and 65% to 70% for children with AML in modern times. We have also learned together about maximizing supportive care and reducing toxicity for our patients so they can go on to live long and healthy lives after treatment. This collaborative focus on the holistic cure of children is a truly special aspect of pediatric oncology.
In 2023, we still face many challenges in curing all children with leukemia. As aforementioned, relapsed AML represents a persistent unmet medical need. We know that we are at a maximal asymptote in terms of chemotherapy intensity for these children and are thus working to integrate the tremendous knowledge gained in recent years regarding AML-associated genetic alterations and their prognostic significance with alternative treatment approaches. We have recently made progress in this domain via opening several pediatric-specific phase I clinical trials of exciting new targeted inhibitors or immunotherapies for relapsed or refractory AML. Another and more nuanced challenge in pediatric leukemia is successfully reducing chemotherapy intensity and associated toxicity for children who have particularly favorable-risk B-ALL, as we are learning that they are highly curable with far less therapy.
What do you hope to see happen in the field? I hope we can address some of these needs and questions more efficiently through the power of team science and participating in innovative clinical trials. I remain hopeful that we will be able to improve cure rates during the next five to 10 years, particularly for children with the highest risk of relapse and the leukemias that are hardest to treat with conventional chemotherapies. I am particularly hopeful that we can credential some of these new targeted therapies not just in the relapsed space, but also bring them forward to children with newly diagnosed leukemias with relevant genetics or biology.
What does your work in pediatric oncology mean to you? As a pediatric oncologist and physician-scientist, I am lucky to have the best job in the world. We wear many different hats in medicine and science that provide a diversity of experiences, and it is the relationships that we have with our patients and their families that are truly inspiring. These children center us and keep us laser-focused on our shared scientific and clinical mission, particularly when things do not go as well as hoped. As a mother, I also have tremendous compassion for the hardships and sacrifices that our families endure in pursuit of successful cancer treatment for their children. I strive to care for them with the same level of excellence that I would expect for my own children.
Can you speak about the value of mentorship? It is critically important to be paired with a mentor who is a good fit for you personally and professionally. I have learned along the way that you can also receive different mentoring components from different people, and the sum is often greater than the parts. It is so important to have someone who is a champion of young people, is generous with their time and creating opportunities, and will focus a bit selflessly on getting the young person to the next stage of their career development.
Because of the tremendous support that I received in my training and still receive from lifelong mentors, I have made it my mission to pay it forward through my own deliberate mentoring of our trainees and young faculty members, especially female physician-scientists. I hope to create for them similar exciting opportunities for their career development that I was so fortunate to have.
What are some of your favorite hobbies and activities outside of work? I love to travel with my family, anywhere and everywhere! We have been lucky to enjoy many fantastic adventures together throughout the world. I have also been quite fortunate to travel to some amazing places with wonderful colleagues through our international collaborations in pediatric oncology.
Besides traveling, I love to read, run, visit art museums, needlepoint, brush up on foreign languages (I am learning Dutch now), and indulge in a bit of “gourmet fashion” shopping. My husband is a pediatric urologist at CHOP and the University of Pennsylvania and a clinical researcher/epidemiologist in pediatric kidney stone disease. Despite our busy work/home life as a dual professional couple, he and I enjoy spending as much time as possible with our two wonderful school-age boys, who are enormous football (soccer) fanatics and begrudgingly practice their cello and viola daily because their mother makes them.
Is there a skill you have that people might be surprised to learn about? I was a competitive water polo player in high school and college (hole defense is tough!), which I suspect that most of my colleagues do not know about me. I also took five years of Latin, which I have found incredibly helpful in medicine, as well as in reading inscriptions on ancient statues while on holiday in Rome.
Sarah Tasian, MD, is Chief of the Hematologic Malignancies Program and the Joshua Kahan Endowed Chair in Pediatric Leukemia at Children’s Hospital of Philadelphia.