Specific Examples of Resident Research
The Fetal Hemoglobin Switch
Three years ago, recent resident Vijay Sankaran and his mentor Stuart Orkin traced the fetal hemoglobin switch to a repressor, BCL11A, that turns off expression of gamma globin (and HbF), allowing beta globin (and HbA) to switch on. This seminal work, published in Proc Natl Acad Sci USA, Science and Nature, answered one of the most important questions in hematology in the past half century and created very important therapeutic possibilities for treating sickle cell disease and thalassemia. Vijay continued to pursue this and related problems during his residency - working both here at Children's and across the river in Cambridge, where he is holds a Visiting Scientist position at the Broad Institute of Harvard and MIT. By following up on thalassemic patients with gene deletions that differ only slightly but lead to markedly different levels of fetal hemoglobin, Vijay tracked down the locus within DNA where BCL11A acts (N Engl J Med ). And, by following up on an old observation that some patients with trisomy 13 have high fetal hemoglobin levels, he was able to identify two micro-RNAs on chromosome 13 that regulate HbF via the Myb gene (Proc Natl Acad Sci USA). More recently, Vijay and his collaborators have shown that sickle cell disease in mice can be cured by silencing BCL11A and reactivating fetal hemoglobin expression (Science) and they have begun the search for small molecules that can cause such silencing and might be effective therapeutics. In other studies, Vijay has discovered that cyclin D3 regulates the size and number of red cells (Genes Dev), and he has found new genes responsible for Diamond-Blackfan anemia (J Clin Invest) and discovered the mechanism underlying that disease (Nat Med). He is embarking on a large scale study of the genetics of hematological disorders and a search to identify natural metabolites that might explain why patients with certain organic acidopathies have high fetal hemoglobins. Vijay is also a great doctor and teacher and was recently honored with an Outstanding Resident Teacher award from the third year Harvard Medical students. He completed his residency last year and was appointed Assistant Professor of Pediatrics. He has recently completed his clinical fellowship year in hematology/oncology.
The Medical Perils of Street Youth
Young people who live on the street - commonly known as 'street youth' - represent a population at great risk for acquisition of HIV and hepatitis C. Much of this excess risk is due to the high prevalence of intravenous drug use and high-risk sexual behavior in this group. Since 2007, recent chief resident Scott Hadland has worked with researchers in his hometown of Vancouver, Canada, to study risk behaviors and the risk they confer for infectious disease transmission among street youth. Scott’s work led to 10 publications during his residency years. He focused on patterns of depression among street youth according to the illicit drugs that they use (J Adolesc Health), and also showed that there is an elevated risk for acquiring hepatitis C among youth who report a history of childhood sexual abuse (Prevent Med). As a resident, Scott was twice nominated for the Society of Adolescent Health and Medicine's New Investigator Award, and was awarded the Academic Pediatric Association's Award for Best Abstract by a Resident at the Pediatric Academic Societies Annual Meeting. His research has been featured in the Canadian press, including in articles in The National Post, The Toronto Star, The Vancouver Sun and MacLean’s Magazine, and has resulted in on-air interviews on CBC Radio One and Global Television. Here in the BCRP, Scott was recognized by the Boston University Medical Students with a teaching award and continued to teach residents in his role as chief resident. In the years ahead, Scott plans to continue his work with at-risk youth as a fellow in adolescent medicine at Boston Children’s Hospital.