A team led by three MGH-affiliated investigators is among 20 recipients of the 2010 Transformative R01 Awards from the National Institutes of Health (NIH). Paola Arlotta, PhD, of the MGH Center for Regenerative Medicine and Department of Neurosurgery, Feng Zhang, PhD, currently a Harvard fellow in Arlotta's lab, and J. Keith Joung, MD, PhD, associate chief of Research for MGH Pathology, will combine their expertise to develop technology that uses light to regulate precisely when and in which cells specific genes are expressed. These five-year grants, which do not have fixed budget caps, support projects with the potential for broad impact throughout medical science. In addition, Conor Evans, PhD, of the Wellman Center for Photomedicine is one of 52 recipients of five-year, $1.5 million New Innovator Awards from the NIH.
Arlotta's team will focus on meeting the challenge of regulating the complex gene expression networks behind both nervous system development and neuronal degeneration associated with conditions like ALS and spinal cord injury. Bringing Arlotta's expertise in the differentiation of neuronal subtypes together with Zhang's studies of light-sensitive proteins and Joung's development of synthetic proteins that recognize and bind to specific genes, the project will create composite artificial proteins that precisely target genes of interest and respond to the application of specific wavelengths of light by either activating or inhibiting gene transcription.
While the technology initially will be applied to understanding and potentially regulating gene expression within the central nervous system, it has the potential to be applied to the regulation of any gene. Earlier this year Joung also received an NIH Pioneer Award for a project that will use the same DNA-recognition proteins to improve the reprogramming of adult stem cells into induced pluripotent stem cells. While Zhang will be joining the faculty at the Broad Institute and the McGovern Institute at MIT next year, he will continue to work closely with his MGH colleagues.
Evans' project also involves the application of light, this time for imaging and improving the treatment of metastatic ovarian cancer. Many regimens used to treat tumors lose their efficacy deep within tissues due to hypoxia -- a lack of oxygen -- which allows cells to become resistant to many chemical and biological agents. Treatments such as radiation therapy and photodynamic therapy (PDT) also require oxygen to mediate their effects. Evans' team will develop new imaging techniques to study the cellular-level impact of hypoxia on treatment resistance in metastatic ovarian cancer. They also will develop and test new PDT agents that do not require oxygen in an effort to stop treatment-resistant disease before it can start.