The step-by-step differentiation of embryonic cells into different types of neurons lays the foundation for our sensory responses, motor commands, and cognitive behaviors. Our research explores such differentiation programs in mammals using a combination of genetic, embryological, and molecular biological methods. While the generation of such neural diversity is a complex process culminating in the most sophisticated of wiring circuits, one simplifying approach is to start by tracking the specification, differentiation, and migration paths taken by specific sets of cells originating from primitive neuroectoderm.
Brigham and Women's Hospital Harvard Medical School
Transcriptional mechanisms of pluripotency and cellular reprogramming
We study key transcriptional and gene regulatory events that lead to the acquisition and maintenance of pluripotency in embryonic stem cells (ESCs). ESCs can self-renew or differentiate to produce most of the cells of the body. These distinct but developmentally relevant cell fates are defined by their unique gene expression signatures. Proper execution of these developmental programs requires the precise tuning of gene expression by transcription factors, coactivators and corepressors. Indeed, aberrant transcriptional regulation is the root of many human diseases including developmental disorders, cancers and degenerative diseases.
The laboratory research focus is to understand the pathways of how small regulatory RNAs are generated, how they exert their gene regulatory function, and their role in the self-renewal and pluripotency of embryonic stem (ES) cells.
Understanding development arising from stem cells using molecular profiles like gene expression microarray, genome wide methylation marks, RNASeq, and histone mark dynamics is currently our state of the art. All of these approaches measure a single dimension of molecular event. How can this be translated to how the cell is functioning at the developmental time point, and how can this be compared between experiments that are using different platforms, cell types, and whatever else?
The Mulligan laboratory continues to be interested in the development of methods for the introduction of genes into mammalian cells, and the application of those methods in a numbers of areas of biology and medicine.
Harvard Department of Stem Cell and Regenerative Biology Brigham and Women's Hospital The Broad Institute
Our goal is to understand how naturally occurring human genetic variation protects (or predisposes) some people to cardiovascular and metabolic disease—the leading cause of death in the world—and to use that information to develop therapies that can protect the entire population from disease.
Dana-Farber Cancer Institute Boston Children's Hospital Howard Hughes Medical Institute
The laboratory utilizes multidisciplinary approaches to understand how mammalian cells choose specific fates and how mutations in important transcriptional regulators lead to developmental defects or malignancy.
Beth Israel Deaconess Medical Center Harvard Medical School
The research carried out in our laboratory focuses on the molecular mechanisms and the genetics underlying the pathogenesis of human cancer as well as in modeling cancer in vivo in model systems such as the mouse.