Our scientific founders have generated breakthrough insights into the essential role of 1C metabolism in driving tumor growth and survival, identifying a wealth of potential therapeutic targets.

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Building on this seminal work, we are advancing product candidates directed at multiple novel 1C targets.

VMoothaVamsi Mootha is an Investigator of the Howard Hughes Medical Institute and directs a laboratory based at Massachusetts General Hospital. He is also Professor of Systems Biology and Medicine at Harvard Medical School and a Senior Associate Member of the Broad Institute.

Dr. Mootha’s research is focused on mitochondria, often termed the “powerhouses of the cell.” Dr. Mootha’s group has utilized tandem mass spectrometry, computation, and biochemistry to characterize the mitochondrial proteome, which now serves as a molecular blueprint for clinical and systematic studies of mitochondria. Dr. Mootha and his colleagues have used this inventory to discover the mitochondrial calcium uniporter, a major channel of communication between mitochondria and the rest of the cell. He collaborates extensively with clinicians and researchers throughout the world, and together they have elucidated more than one dozen disease genes that underlie severe, metabolic diseases. His team has developed a number of computational tools that are used widely by the community.

Dr. Mootha received his undergraduate degree in mathematical and computational science at Stanford University and his MD in 1998 from Harvard Medical School in the Harvard-MIT Division of Health Sciences and Technology. He subsequently completed his internship and residency in internal medicine at Brigham and Women’s Hospital in 2001, after which he completed postdoctoral fellowship training at the Whitehead Institute.

Dr. Mootha has received a number awards, including a Macarthur “Genius Grant,” and is an elected member of the National Academy of Sciences.

JRabinowitzJoshua Rabinowitz is Professor of Chemistry and Integrative Genomics at Princeton University. He is a Member of the Rutgers Cancer Institute of New Jersey and the Lewis-Sigler Institute at Princeton University.

Dr. Rabinowitz’s lab studies metabolism from the system biology perspective. His group develops methods that combine mass spectrometry, isotope tracers, and mathematical modeling to quantitate metabolic flux. Using these methods, Dr. Rabinowitz attempts to understand basic principles of metabolic flux control. His lab has found that most enzyme active sites are saturated, with competition between metabolites determining enzyme activity. It is now combining metabolomics with proteomics to investigate the relative importance of active site competition, allostery, and enzyme concentrations in overall metabolic regulation. Dr. Rabinowitz’s lab is also interested in identifying the contributions of different pathways to producing key high-energy cofactors, such as ATP, NADPH, and activated one-carbon donors. Recently, it identified an unexpected tie between two of these cofactor systems, with folate metabolism playing a significant role in redox homeostasis. The lab collaborates broadly, with one notable collaboration having led to discovery of the oncometabolite 2-hydroxyglutarate. Methods developed in the lab are widely used in the cancer metabolism community.

Dr. Rabinowitz received his undergraduate degrees in mathematics and chemistry from the University of North Carolina-Chapel Hill with highest honors. He subsequently completed his MD/PhD at Stanford University in the laboratory of Harden M. McConnell, graduating in 2001. Thereafter, Dr. Rabinowitz founded Alexza Pharmaceuticals, inventing the Adasuve inhaler (now FDA-approved for treatment of acute agitation). In 2004, he joined the faculty of Princeton University. There he has received several honors, including the Beckman Young Investigators Award, the NSF Career Award, and the Agilent Thought Leader Award.

DSabatiniDavid Sabatini is a Member of the Whitehead Institute for Biomedical Research, Senior Associate Member of The Broad Institute, and Member of the Koch Institute for Integrative Cancer Research at MIT, as well as a Professor of Biology at the Massachusetts Institute of Technology. He is also an Investigator of the Howard Hughes Medical Institute.

Dr. Sabatini and his lab at the Whitehead Institute study the basic mechanisms that regulate cell growth, the process whereby cells and organisms accumulate mass and increase in size. These pathways are often deranged in human diseases, such as diabetes and cancer. A major focus of the lab is a cellular system called the Target of Rapamycin (TOR) pathway, a major regulator of growth in many eukaryotic species. Work in Dr. Sabatini’s lab has led to the identification of many components of the pathway and to an understanding of their cellular and organismal functions. Dr. Sabatini is also interested in the role of metabolism in cancer and in the mechanisms that control the effects of dietary restriction on tumorigenesis. In addition to the work on growth control and cancer, Dr. Sabatini’s lab has developed and is using new technologies that facilitate the analysis of gene function in mammalian cells. The lab developed ‘cell-based microarrays’ that allow one to examine the cellular effects of perturbing the activity of thousands of genes in parallel. Dr. Sabatini is a founding member of The RNAi Consortium (TRC) of labs in the Boston area that is developing and using genome-scale RNA interference (RNAi) libraries targeting human and mouse genes.

Dr. Sabatini received his BS from Brown University magna cum laude and his MD/PhD from Johns Hopkins University in 1997. He completed his thesis work in the lab of Dr. Solomon H. Snyder in the Department of Neuroscience. Later in the same year, Dr. Sabatini was appointed a Whitehead Fellow at the Whitehead Institute for Biomedical Research. This was followed in 2002 by a dual appointment as a Member at the Whitehead Institute and Assistant Professor of Biology at the Massachusetts Institute of Technology. Dr. Sabatini has received a number of distinctions, including being named a W. M. Keck Foundation Distinguished Young Scholar, a Pew Scholar, and a TR100 Innovator, as well as the 2009 Paul Marks Prize for Cancer Research, the 2012 Earl and Thressa Stadtman Scholar Award from ASBMB, the 2013 Feodor Lynen Award from Nature, and most recently the 2014 NAS Award in Molecular Biology.