Ramiro Massol, PhD
2010 DICP Faculty Fellowship Alumni
RAMIRO MASSOL, PhD, Instructor in Pediatrics, Harvard Medical School; Children’s Hospital Boston Pediatrics/GI Division
Mentor: Wayne Lencer, M.D., Head of the Department of Pediatrics, Children’s Hospital Boston; Egan Family Foundation Professor of Pediatrics, Harvard Medical School
Department Chair: Gary Fleisher, M.D., Chief of the Division of Gastroenterology, Children’s Hospital Boston; Professor of Pediatrics, Harvard Medical School
Project Title: "Biogenesis and Maintenance of the Enterocyte Brush Border"
The small intestinal epithelial cells (enterocytes) provide the brush border (BB) apical membrane, which is a scaffold essential for the digestion and absorption of nutrient solutes and a barrier against invading pathogens, toxins and antigens. Enterocytes and local immune cells also interact with the commensal flora to identify pathogenic organisms and regulate subsequent immune responses. As expected, damage to the enterocytes leads to severe diarrhea, malnutrition and facilitates pathogen invasion and local inflammation. The formation of the BB involves specialized vesicles that deliver apical structural components like microvilli (MV) to areas of cell-cell contact. These MV-containing vesicles have been observed in patients suffering Microvillus Inclusion Disease (MID), a life-threatening autosomal recessive hereditary intestinal disorder of infancy characterized by shortened and mislocalized MV and mislocalized apical proteins. Nonsense mutations in the actin-motor protein myosinVb has been proposed to be the cause of MID. Similar abnormalities were observed upon silencing Rab8a, a small GTPase that interacts with MyosinVb. Both MyosinVb and Rab8a regulate membrane sorting steps from the recycling endosomal compartment, and hence this compartment is decisive in regulating BB structure and function. My research will use a combination of biochemical, morphological and genetic assays to identify and characterize regulators of the different membrane trafficking pathways involved in cell polarity and BB formation and maintenance. The outcome of this project could affect our ability to intervene in diseases linked to cell polarity, mucosal barrier function, and regulation of ion transport.
Ramiro Massol, PhD, HMS instructor in Pediatrics at Children’s Hospital – Boston, will work on a project titled “Biogenesis and Maintenance of the Enterocyte Brush Border”. He is seeking to identify and characterize regulators of membrane trafficking pathways involved in cell polarity and brush border formation and maintenance. His research may lead to a better understanding of diseases linked to cell polarity such as Microvillus Inclusion Disease, a life-threatening autosomal recessive intestinal disorder of infancy.