The first year of the fellowship is fully dedicated to research under the direct supervision of Michael Hsieh, M.D., Daniel Casella, M.D., and Hans Pohl, M.D. The overall goal of the research year is to expose fellows to basic science research and to build a basic understanding of the responsible conduct of research which will be broadly useful across future career paths. Incoming fellows will review ongoing basic science projects with Drs. Hsieh and Casella and identify a project to focus on during their research year. Fellows are welcome to participate in multiple projects, however given that there is only one year of dedicated time we feel that fellows will have the most opportunity for success with a narrow focus.
Dr. Hsieh’s lab is currently focused on understanding the immunology of urinary tract infections and inflammation-induced bladder pathology. He is also collaborating with Dr. Pohl to understand how the microbiome, the collection of microbes in and on our bodies (many of which are not cultivatable but detectable through molecular methods), affects risks of urinary tract infection. Dr. Hsieh's immunological work is based on mouse models of urinary tract infection and overactive bladder. His group is exploring how various arms of the immune system play a role in UTI. The laboratory is also therapeutically exploiting host immunomodulatory proteins produced by urogenital parasites, the most evolutionarily advanced pathogens of the human urinary tract, for hemorrhagic cystitis and bladder hypersensitivity.
Dr. Casella’s lab is located on the main campus at Children's National Hospital and has two ongoing projects, the first of which is working to understand the molecular mechanisms of cloacal membrane and genital tubercle development. Utilizing the mouse embryo as a model, the aim of this project is to characterize a unique population of senescent cells in the developing genital tubercle. Through the use of inducible genetic knockouts and molecular profiling techniques we hope to gain an understanding of the growth factors secreted by these “developmentally senescent” cells and their role in patterning the genital tubercle and urethra.
The second project in Dr. Casella’s lab is centered on the ability of low intensity focused ultrasound to stimulate targeted neurons. Dr. Casella has recently demonstrated the ability of targeted ultrasound of the posterior tibial nerve to temporarily suppress bladder contraction in a rodent model. He is currently working to refine his technique and generate the preliminary data required for a clinical trial in human subjects. Ultimately Dr. Casella hopes to develop targeted low intensity ultrasound as a non-invasive and painless outpatient treatment for pediatric bladder and bowel dysfunction.