Posted on June 18, 2019
In June 2019, Douglas Stewart, M.D., was awarded scientific tenure by the NIH and promoted to senior investigator in the Clinical Genetics Branch. His dual expertise in medical genetics and internal medicine has allowed him to effectively pursue the contribution of germline genetic variation to cancer etiology, with a primary focus on genetic mutations that confer high cancer risk. In particular, he has made substantive contributions to our understanding of risk and phenotype in two distinct cancer-prone disorders, the neurofibromatosis type 1 (NF1) and DICER1 syndromes.
Early in his career, Dr. Stewart’s seminal work on NF1 led directly to important changes to clinical care for these patients, specifically by revising the pathologic classification of atypical neurofibromas, with the goal of earlier diagnosis. Though patients with NF1 have been intensively studied for more than a century, Dr. Stewart identified and characterized novel features of NF1, including pulmonary hypertension, gastrointestinal stromal tumors, glomus tumors, and genetic modifiers.
Over the last several years, Dr. Stewart has built the world’s largest, most well-characterized cohort of patients with germline DICER1 mutations, reporting many novel clinical manifestations of the syndrome. His findings have refined the understanding of the DICER1 mutational spectrum and informed patient care, management, and led to the first ever DICER1-syndrome surveillance guidelines.
Dr. Stewart is capitalizing on novel, emerging opportunities through his leadership of a new program in public health genomics, integrating classical “phenotype-first” genetics and the newer paradigm of “genotype first” to advance the identification of new syndromes, mechanisms, and biology. In a collaboration with Geisinger Health System in Pennsylvania, Dr. Stewart demonstrated how the genotype-first strategy can determine and refine the prevalence, penetrance, and phenotype of DICER1-carriers. Based on the success of the DICER1 study, he is expanding the effort to other gene-focused studies within the Division.