Stavros S. Niarchos Professor in Pediatric Cardiology
Professor of Pediatrics
Early work in the Lyden Lab resulted in several fundamental discoveries that involve the role of bone marrow-derived stem and progenitor cells in tumor vasculogenesis and in metastasis. Using pediatric and adult cancer models, Dr. Lyden and his colleagues made a pivotal discovery in the metastatic cascade revealing that tumor-secreted factors induce the formation of microenvironments in distant organs conducive to tumor cell survival and outgrowth. Remarkably, these microenvironments are generated prior to tumor cell arrival at these sites, an observation that led Dr. Lyden and his team to develop the concept of the "pre-metastatic niche". Work in the pre-metastatic niche has been translated to clinical care leading to advances in prediction, imaging and targeting of early metastatic disease progression. Dr. Lyden also found that tumor-secreted microvesicles, known as exosomes, initiate pre-metastatic niche via induction of vascular leakiness, stromal cell education and immunoregulation through key proteins (i.e., oncoproteins, integrins) and nucleic acids in exosomes. Tumor exosomes not only initiate pre-metastatic niche formation, but also determine organotropic metastasis, a hypothesis proposed by Stephen Paget more than 120 years ago. Dr. Lyden’s work has engendered a new appreciation for how primary tumor cells dictate future sites of metastasis by decoding how cancer-derived exosomes mediate intercellular communication. In addition, the Lyden team demonstrated the presence of double-stranded DNA in tumor exosomes. Thus, exosomal molecules may serve as valuable biomarkers for tumor detection and to follow metastatic progression. Most recently, Dr. Lyden has identified specific exosome subpopulations (Exo-Large vesicles and Exo-Small vesicles) and discovered a new subset of particles known as exomeres, which have distinct functional roles in the systemic effects of cancer. Dr. Lyden’s group has a long-standing interest and collaborations to study the role of exosomes in pediatric cancers, such as medulloblastoma, osteosarcoma, neuroblastoma and leukemia. Last but not least, Dr. Lyden is collaborating with faculty in the Department of Pediatrics to elucidate the functional roles of exosomes and exomeres in other pediatric disorders, such as autism and systemic lupus erythematosus.