Faculty Spotlight: Transform Precision Medicine With Sarah Henrickson, MD, PhD

Members of the lab of Sarah Henrickson, MD, PhD.

Editor’s Note: Welcome to our monthly Faculty Spotlight series, in which we sit down with faculty members at Children’s Hospital of Philadelphia Research Institute to learn more about their research and roles. Through these spotlights, our readers meet the diverse, dedicated, and distinctive individuals who lead our research community in our mission to improve children’s health. This year, we will be asking our featured scientists about mentorship — why it matters and how it has influenced their careers. In this Q&A, we feature scientist Sarah E. Henrickson, MD, PhD, in the Division of Allergy and Immunology. Stay tuned for more from our Faculty Spotlight series throughout this year!

How long have you been at CHOP. and what is your research speciality?

I’ve been at CHOP since June 2013, when I started as a third-year pediatrics resident. I had started residency at a program in Boston, and CHOP welcomed me with open arms as a transfer when my husband started his lab at Princeton. I was grateful for that openness when I came to CHOP, and it has remained a defining trait of this institution for me!

We are working on better understanding human immune function and how perturbations of that system affect our susceptibility to worse outcomes with infection, autoimmunity, and malignancy. We focus on pediatric diseases of chronic inflammation (e.g., obesity and asthma) and primary immune deficiency — it turns out there are a lot of shared impacts on immune function! Our questions come from the details of human disease, and then we work with human cells and animal models of disease, as appropriate, to assess how T cells are affected in similar (and potentially targetable) ways.

Why did you choose to focus on that specialty?

I am fascinated by common threads between common inflammatory diseases, like obesity and asthma, and rare primary immune deficiencies. In the former, environmental factors lead to dysregulated inflammatory cytokine signaling, and in the latter, monogenic diseases can amplify signaling in those same pathways. In both cases, we can hunt for altered functional states of immune cells that may be contributing to disease — and may be modulable with therapies. It is directly related to my work in clinic as a pediatric Allergy/Immunology physician, and it is incredibly fulfilling to take care of patients in clinic and study their disease processes in our lab team.

Sarah Henrickson, MD, PhD

Can you tell us about a current research project that you are excited about?

We are currently focusing on the shared presence of a specific, targetable form of T cell dysfunction (known as T cell exhaustion) in obesity and a set of monogenic primary immune deficiencies that mimic chronic inflammation due to changes in cytokine signaling pathways. By studying both, it is both possible to better understand the basic science mechanisms underlying T cell exhaustion and may lead to novel therapeutic strategies for both rare primary immune deficiencies and more common inflammatory disorders.

What are the long-term research questions you hope to answer?

I think that the way we currently see precision medicine needs to transform in the context of rare (and potentially common) disease. In monogenic diseases, given that these mutations affect cells across the patients’ and cells’ lifetime, it is logical that there will be a lot of compensating factors in play. I am fascinated by the idea of putting a defined focus on how cell function is altered and targeting functional impairment, rather than aiming exclusively for the pathway that contains the mutation. So, I hope to move forward with defining more functional assays that facilitate identification of targetable immune dysfunction in pediatric disease.

How has mentorship influenced your career?

I have been lucky throughout my career to have worked with remarkable mentors. The first was a chemistry teacher in high school, Doris Sandoval, who encouraged my love of science. I was part of a high school science magnet program and was able to work at the National Institute of Standards and Technology on early stages of DNA nanopore sequencing, which was incredibly motivating. I was also incredibly lucky to have Dr. John Kasianowicz as a mentor who valued high schoolers as researchers in lab.

In college, I started working in immunology, after falling in love with the subject in an undergraduate course. I spent a year at the National Institutes of Health between college and MD/PhD and my mentor, Lou Staudt, encouraged my interest in systems immunology. My PhD advisor, Dr. Uli von Andrian, fostered my fascination with cellular immunity and the factors that control T cell activation. 

Finally, my post doc advisor, Dr. John Wherry, modeled the power of merging human and animal model studies to quantify complex biological systems and interrogate human disease mechanisms, as well as how to pick important questions and build teams. At every stage, I have had remarkable mentors who have made my career possible by teaching me skills, strategies, and both scientific expertise and how to learn most effectively. I hope that I can do that for my trainees moving forward; I will certainly do everything I can to make that happen!