Defining the molecular mechanisms of somatic cell reprogramming

The development of methods to “reprogram” adult cells such as skin cells by simultaneously expressing four specific factors — Oct3/4, Sox2, c-Myc and Klf4 — in order to create cells resembling embryonic stem (ES) cells is a major breakthrough in stem cell biology. Our ability to generate these cells, which are known as induced pluripotent stem (iPS) cells, will allow us to obtain stem cells capable of maturing into any tissue type, which is critical for research and has great therapeutic potential, without the controversial use of embryos. We envision that human iPS cells generated from a patient could be used to generate specific cells or tissues for cell replacement therapies for that individual patient, without stimulating an adverse immune response. Certain disease-specific iPS cells could also be differentiated into diseased tissues to study the causes of those diseases or to screen for drugs to treat them. Differentiated cells from iPS cells could also be used for toxicology tests before a drug is given to patients. Therefore, iPS cell technology may make individualized medicine a reality in the future. However, molecular changes that underlie reprogramming of body cells are not yet well understood and must be defined before iPS cells can be safely used for patient-specific therapy.

In this study we will undertake biochemical and molecular analysis to try to understand cellular changes mediating reprogramming. These studies should help us to develop novel strategies to make reprogramming more efficient so that iPS cells can be generated on a large scale for use in regenerative medicine, individualized medicine and drug discovery.