2009 HSCI Radcliffe Fellow to use tissue engineering and systems biology to study endometriosis

Each year, the Radcliffe Institute for Advanced Study invites a group of scientists, artists, historians, sociologists, economists, and literary scholars from around the world to form a multidisciplinary community at Harvard for a year where they are provided the opportunity to pursue their scholarly or artistic projects. Since 2007, HSCI and Radcliffe have collaborated to sponsor a fellow whose work is both related to stem cell science and interdisciplinary in nature.

This year, Linda Griffith, PhD, a professor at Massachusetts Institute of Technology, was selected for the HSCI Radcliffe Fellowship. She will spend her sabbatical year working to integrate tissue engineering with systems biology with the aim of illuminating complex disease processes not well replicated in animal models. While at Radcliffe, she will apply this approach to endometriosis, a disease that afflicts about 10 percent of women in their childbearing years. In particular, she will develop new tools to enable the visualization of complex inflammatory networks in cell cultures from afflicted patients, revealing what is functionally different about their cells.

In the broader scope of her research program, which includes regenerative medicine and drug discovery applications, Griffith plans to use human mesenchymal stem cells and a combination of molecular engineering, nanofabrication, and microfabrication to build extracellular microenvironments to study how stem cells probe their local microenvironments and regulate their behavior by releasing growth factors, creating feedback loops that help cells adjust to external cues.

This cell-cell communication project has also been recently awarded a Transformative RO1 grant, a type of NIH grant that supports new, bold ideas that may require significant resources to pursue and need the flexibility to work in large, complex teams. The work has already begun through a foundation-supported collaborative project with Keith Isaacson, MD, gynecology surgeon at Harvard Medical School, to study the cellular processes underlying this disease, including the possible role of stem cells.

In her career, Griffith has repeatedly proven to be a pioneer and leader in the field of tissue engineering, which began its upward trajectory about 20 years ago with a series of dramatic demonstrations that new tissue could be grown in vivoby combining degradable surgical polymers with a source of donor cells. As an assistant professor in the early 1990s, Griffith and her clinical collaborators showed that new cartilage tissue could be generated in vivo by transplanting cartilage cells into a porous, degradable scaffold. These early demonstrations illustrated the enormous potential for combining scaffolds with cells to treat a range of clinical problems; however, commercial scaffold fabrication presented a barrier to clinical translation.

Griffith tackled this problem by teaming up with colleagues in mechanical engineering and materials science to invent “3D printing,” a manufacturing process that literally “prints” three dimensional scaffolds. The process can be used with almost any kind of material and can include patient-specific images from MRI or CT scans. As a result, 3D printing is now used in the manufacture of several successful clinical products.

What continues to set Griffith apart is her ability to combine basic cell and molecular science with innovative technological applications. She was one of the first tissue engineers to dig deeply into cell biology as the basis for designing new biomaterials and continues to use this approach to manipulate signaling pathways in mesenchymal stem cells to illuminate facets of their basic biology.

Griffith was motivated to apply for the Radcliffe Fellowship in part by her desire to raise awareness among the stem cell community of endometriosis and other women’s diseases that may have stem cell pathologies. She is looking forward to the chance to think more broadly about the societal impact of her research while taking advantage of the wide range of HSCI affiliated institutions to hold discussions not only on the science itself but on the impact that both science and society have on women’s health issues.