Todd R. Golub
Todd Golub is director of the Broad Institute of MIT and Harvard, and a founding core member of the institute. He is also a member of the faculty of the Dana-Farber Cancer Institute and Harvard Medical School.
Golub is a world-renowned physician-scientist who pioneered the application of genomics to cancer biology and therapeutic discovery. He is one of the first researchers to use genomic approaches to molecularly characterize human tumors, laying the foundation for the use of genomics to classify, diagnose, and treat cancer. Throughout his career, Golub has advocated for the free, rapid sharing of large-scale genomic data and tools to accelerate the pace of biomedicine, and is deeply committed to patient-focused research.
Early in his career as a pediatric oncologist and cancer researcher, Golub made key discoveries on the genetic and molecular origins of the most common form of childhood leukemia, acute lymphoblastic leukemia (ALL). These fundamental insights led to changes in treatment that are now the standard of care. This groundbreaking research stemmed from Golub’s dual role as a physician and scientist, and it helped crystallize his strongly held view that continually learning from patients—in an unbiased and systematic way—is the surest route to uncovering the root causes of disease and identifying novel, effective treatments.
Golub’s innovative use of gene-expression analysis to classify tumors catalyzed the creation of new genomic tools and approaches that have had a lasting impact on cancer research and drug discovery. Together with scientists from across Broad and partner institutions, Golub helped develop many of these tools, including analytical methods for studying genome-wide expression profiles of tumors, such as Gene Set Enrichment Analysis (GSEA). He led other large-scale projects, such as the Connectivity Map, which uses gene expression profiles to analyze cellular perturbation, with the aim of discovering relationships between cell states, gene function, and drug action.
Golub and his colleagues have also launched ambitious projects to characterize the biology of cancer cell lines, including molecular barcoding approaches that allow scientists to much more rapidly test drugs for anti-cancer potential across hundreds of cell lines simultaneously. This barcoding method, called PRISM, has also been used by the Golub lab to generate the Metastasis Map, which is revealing the mechanisms by which tumor cells spread and survive in different locations in the body. Golub has initiated a major effort at Broad, known as the Drug Repurposing Hub, to curate and characterize the biological effects of thousands of existing drugs—many already proven safe in humans—with the aim of uncovering novel uses, especially for cancer treatment.
Dipti Nayak
Based on the evolutionary history of conserved molecules and cellular features, life on Earth can be divided into three distinct domains: Bacteria, Eukarya, and the enigmatic Archaea. Our knowledge of the domain-specific molecular and cellular attributes of bacterial and eukaryotic organisms is comprehensive. However, despite their abundance and importance, very little is known about the cell biology or physiology of archaea, partially due to the lack of well-developed model organisms. The goal of the Nayak lab is to use to methanogenic archaea as a model system to explore various facets of archaeal biology including methanogenesis, a metabolic trait that is unique to, and widespread in, Archaea.
Methanogenesis, methane production coupled to growth and energy conservation, is the only physiological attribute that is exclusively present in Archaea. Moreover, the scope of methanogenic archaea has broadened since their initial discovery: now, representatives can be found in all major phyla across the domain. Significantly, methanogenic archaea produce 1 gigaton of methane annually, which amounts to ca. 2/3rd of the emissions of the second most abundant greenhouse gas with a warming potential 25-times that of carbon dioxide. Additionally, methanogens are important members of the microbial community in humans, other mammals and insects, as well protists. Taken together, a uniquely archaeal identity, in addition to wide ranging implications for climate change and human health, makes methanogens ideal model systems to investigate the molecular and cellular biology of archaea.
The Nayak lab is developing a wide range of genetic, genomic, and biochemical tools for methanogenic archaea of the genus Methanosarcina as well as implementing these techniques to study their physiology, metabolism, evolution, and cell biology.