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Faculty Spotlight: Combining Critical Care and Translational Immunology with Robert (Brad) Lindell, MD

Published on February 26, 2024 in Cornerstone Blog · Last updated 1 month 1 week ago
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Robert (Brad) Lindell, MD

Robert (Brad) Lindell, MD

Editor’s Note: Meet the diverse, dedicated, and distinctive faculty who are discovering and developing pediatric life-changing solutions at Children's Hospital of Philadelphia Research Institute, in our monthly Faculty Spotlight series. This year, we're celebrating our internal grant recipients who are pursuing new avenues of research with this dedicated funding support. Although we cannot feature all the award recipients in this series, we congratulate their continued hard work and scientific contributions to pediatric research. In this Q&A, we meet Robert (Brad) Lindell, MD, recipient of the Mentored Research Pilot Grant for Junior Faculty. Stay tuned for more from our Faculty Spotlight series throughout the year.

How long have you been at CHOP?

I came to CHOP in 2012 for pediatrics training and continued to stay as a chief resident, a pediatric critical care fellow, and now as a faculty member since 2019. Throughout my time at CHOP, I've enjoyed tremendous support and mentorship that have made my decisions easy. I never intended to become a CHOP "lifer," but I now have three Eagles-loving children, and I think I am here to stay.

Can you tell us a little about your research specialty?

My research focuses on sepsis, which is the disease that develops when children become critically ill in the setting of a dysregulated immune response to infection. Pediatric sepsis is a complex, heterogeneous disease, and it is the leading cause of death of hospitalized children in the United States. My lab focuses on the mechanisms that underlie immune dysregulation in sepsis, small molecules that can modulate immune signaling in sepsis patients, and computational approaches to identify patients who may benefit from precision therapy.

Jack Downes, MD, pioneered the development of pediatric critical care medicine in the United States, opening the first pediatric intensive care unit here at CHOP in 1967. His vision – that the sickest patients in the hospital should be cohorted together – is still the unifying principle for our field. This disease agnostic cross-disciplinary approach has led to remarkable advances in the care of pediatric lung injury, sepsis, traumatic brain injury, and cardiac arrest over the last 50 years.

Why did you choose to focus on sepsis as a research specialty?

When I came to CHOP for training, I planned to become a pediatric oncologist. Precision medicine fascinated me as a medical student, and no one was better at precision medicine than oncologists. Worldwide collaboration in pediatric oncology had rapidly improved outcomes for many children with cancer, and I wanted to be part of that team.

During my clinical training, I realized that I loved the fast-paced, high-intensity environment of pediatric critical care. I loved the diversity of pathologies and patients who I could care for on a daily basis. I enjoyed being part of a multidisciplinary team, working with students and residents from across campus. Mentored by Julie Fitzgerald, MD, PhD, MSCE, I realized there was also a need for precision medicine approaches in critically ill patients. Ultimately, pediatric critical care medicine combined the clinical care that I most wanted to practice with translational science that I found both challenging and exciting.

What is a new avenue of research you're able to explore as result of the Junior Faculty Award?

The award provided the support I needed to open the lab, and it helped us build a large, longitudinal multi-omics sepsis dataset. That project has led to identification of protective and pathologic immune responses, as well as to novel proteomic signatures that may help us identify patients with increased risk of adverse events.

These insights have led to other successful grant applications – one focused on febrile children in the emergency department and another studying dysregulated immune responses in critically ill children without sepsis. Several more are in the works.

I've also been fortunate to grow my mentorship team to include Nuala Meyer, MD, MS, John Wherry, PhD, and Sarah Henrickson, MD, PhD – all leaders in the field of translational immunology.

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

The sickest children in our study experience something called a "cytokine storm," which is a life-threatening systemic inflammatory syndrome that causes immune cell hyperactivation and widespread organ injury. By benchmarking against critically ill children without cytokine storm, we have identified three distinct signaling pathways that can be dysregulated in these patients. Each pathway can be targeted using medications, and our next step is to test response to candidate therapies using patient samples in cell culture.

The goal of this reverse translation approach is to identify a group of "treatable traits" that could cause critical illness in an individual child. We still have a long way to go, but I hope this is the first step to a successful precision-medicine paradigm for these high-risk children.

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

My major goal is to leverage translational immunology insights to improve the care we provide to patients in the pediatric intensive care unit. Immunology is a rapidly developing field, and at CHOP we work closely with the University of Pennsylvania, a national leader in the application of translational immunology to diagnose and treat disease.

At its core, the immune system is a complex network of molecular sensors that continuously surveils the human proteome. In addition to causing some forms of critical illness (including sepsis), the immune system has the power to monitor for and identify pathology throughout the body, essentially functioning as a sensory organ. As immune technologies continue to advance, I expect we will find additional roles for both immunodiagnostics and immunotherapeutics in pediatric critical care medicine.