2009 marks the inaugural year for the HSCI Mignone Fellows program, funded by The Roberto and Allison Mignone Fund for Stem Cell Research. This fund was established with a generous gift from Roberto A. Mignone ’92, MBA ’96, and Allison H. Mignone ’94, MBA ‘95, to support graduate student research in stem cell and regenerative biology on HSCI sponsored research projects. This year’s Mignone Fellows, Tim Ahfeldt and Elena Piskounova, are working on research being carried out by HSCI’s Stem Cell Regulation Project.
Ahfeldt, who works in the laboratory of HSCI and Harvard Department of Stem Cell and Regenerative Biology (SCRB) faculty member Chad Cowan, PhD, at Massachusetts General Hospital, is working to establish a highly efficient viral system to direct stem cells into adipocytes (fat cells). Investigating in vitro derived adipocytes will yield insights into obesity with the ultimate goal of developing therapies for obesity-associated medical conditions such as cardiovascular disease and type 2 diabetes.
“The Harvard Stem Cell Institute is an open and collaborative environment and a great place to work. The Roberto and Allison Mignone award represents a tremendous honor. As an early career scientist, I especially appreciate the mentorship that accompanies the Mignone award,” said Ahfeldt.
Working in the laboratory of HSCI Principal Faculty member Richard Gregory, PhD, at Children’s Hospital Boston, Piskounova is focused on trying to reveal the underlying mechanism of how piRNAs, a class of small RNA molecules, are generated. These molecules interact with proteins and other small RNAs, which play a central role in “RNA silencing” pathways that regulate many cellular processes in stem cells.
The HSCI Stem Cell Regulation Project comprises a group of five HSCI Principal Faculty members performing collaborative research at two Harvard-affiliated hospitals. Along with Cowan and Gregory, the group of investigators includes Carla Kim, PhD, at Children’s Hospital Boston and SCRB faculty member Paola Arlotta, PhD, and Hanno Hock, MD, PhD, both at Massachusetts General Hospital.
The goal of this collaborative project is to deepen our knowledge of the molecular regulation of stem cell identity, maintenance, and differentiation in normal development and disease processes. Experiments are being conducted on differentiation of stem cells into neuronal subtypes, development and maintenance of adipose tissue, the role of microRNAs in regulating stem cell fate, transcription factors in maintenance of hematopoietic (blood) stem cells, and pathways regulating stem cell function in normal lung biology and lung cancer.
Two additional graduate students have been awarded fellowships under The Sternlicht Director’s Fund, a grant program initiated in 2007 by a generous gift from Barry S. Sternlicht, MBA ’86, and Mimi Reichert Sternlicht to provide support for graduate students using stem cell research to study diabetes. The 2009 Sternlicht Fellows, Sinisa Hrvatin and Adriana Tajonar, are currently conducting research under the direction of HSCI Co-Director Doug Melton, PhD, in Harvard’s Department of Stem Cell and Regenerative Biology.
Hrvatin is working on the problem of how to direct the differentiation of pancreatic progenitor cells into mature beta cells, which would resolve a major obstacle in the field. Currently, researchers are stuck at the intermediate stage of pancreatic progenitors in coaxing embryonic stem cells through the developmental stages that ultimately result in insulin-producing beta cells normally found in the pancreas.
For stem cell therapies to become a reality, it may be necessary to generate large numbers of cells at different developmental states. Tajonar recently conducted an experiment to determine which genes keep human embryonic stem cells in an undifferentiated state while simultaneously promoting selfrenewal, the mechanism by which cells multiply. Her work resulted in several promising finds, including identification of a transcription regulator previously not known to impact self renewal. She is now using these genes to determine how they might be used to multiply cells in each developmental state on the path from embryonic stem cell to mature beta cell.