Boston Children's Researcher Spotlight:
Carla Kim, PhD, Principal Investigator in the Stem Cell Program

In this monthly new showcase, TIDO will highlight an up and coming researcher within the Boston Children's community by asking the researcher three questions about their research. This month, we had the pleasure of interviewing Dr. Carla Kim, PhD, principal investigator in the Stem Cell Program. Dr. Kim seeks to understand the relationships between stem cell biology, cancer biology and lung biology.

Carla Kim, PhD

Q: What drives you as a scientist?

The unique opportunity we have to understand disease and the excitement of discovering new ways to understand biology. When I was deciding on a career path as an undergraduate, I was frustrated that physicians would let a patient know they have, or might develop a disease, but that there was often no way to intervene. I wanted to pursue a career that would allow me to explore and understand diseases and eventually prevent or treat them. I feel fortunate to have been able to establish my own research program and to realize the joy of making new discoveries.

Q: What is unique about your research?

We have pioneered the use of stem cell biology approaches for the lung and lung cancer. My lab studies lung stem cells, which itself is unique, since we (and I as a postdoc) were the first to isolate cells from the adult lung with stem cell activity. We used cell sorting to isolate and characterize lung stem cells and discovered bronchioalveolar stem cells (BASCs), a lung epithelial stem cell population that contributes to airway and alveolar lineage injury repair and tumorigenesis. The field of lung stem cell biology is less than 10 years old and there are many more questions to answer.

Based on these initial findings, my lab’s research has continued to make significant progress. We have developed an orthotopic transplantation assay for lung tumor-propagating cells (TPC), the cells that have capacity to recapitulate the tumor. We identified the first bona fide lung TPCs, which provide new opportunities to study targets for lung cancer therapy. We provided evidence that the genetic status of a tumor is an important consideration in TPC studies.

Most recently, we created three-dimensional co-culture and co-transplantation organoid systems that demonstrate the potential of BASCs. Now we can visualize the formation of airway- and alveolar-like structures from single BASCs, and have a way to precisely define how lung stem cell differentiation is controlled at the molecular level. Using these organoids, we have shown that lung epithelial stem cells and lung endothelial cells interact in a novel BMP4-NFATc1-TSP1 signaling axis that drives lineage-specific differentiation. This is one example of how our work has begun to define the molecular underpinnings of differentiation.

Q: How might your research be translated into a therapy for lung cancer?

It is not clear how and if lung stem cells are either: (1) at the root of lung diseases including cancer (are stem cells defective, leading to the disease?); or (2) a unique therapeutic opportunity to intervene in disease. We have only recently discovered how to identify TPCs in murine lung cancers, and now we need to understand if similar cells regulate human lung cancers. Exactly how differentiation is controlled and how a multi-potent stem cell knows how to differentiate to repair injured tissue are unclear. Understanding these concepts could lead to new pathway discoveries as therapeutic targets in lung disease and lung cancer.

In particular, we recently created 3D lung stem cell co-culture assays for differentiation. With this system in place, we can begin to ask if stem cells or their supporting stromal cells are defective in lung diseases and cancer.

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