Joshua Rabinowitz, director of the Ludwig Institute for Cancer Research Princeton Branch, is a professor in the Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics at Princeton University. Since 2008, Rabinowitz has also been a member of the Rutgers Cancer Institute of New Jersey. After obtaining his M.D. and a Ph.D. in biophysics from Stanford University, Rabinowitz co-founded Alexza Pharmaceuticals and served as vice president for research until 2004, when he joined Princeton University. Rabinowitz has received several awards for his scientific contributions, including the Allen Distinguished Investigator Award, the NIH Pioneer Award, the CAREER Award of the National Science Foundation and the Beckman Young Investigator Award.
Joshua Rabinowitz focuses his research on two broad questions: What is the quantitative flow (flux) through different metabolic pathways? How is this flux controlled? These questions go to the essence of how metabolism functions. To answer them, the Rabinowitz laboratory develops methods and technologies that blend mass spectrometry and computational analysis and applies them to biological experimentation. Rabinowitz’ innovations and technologies have been widely adopted in the research community and have enabled identification of many previously unappreciated metabolic phenomena in viral infections, bacteria, yeast, and mammals. His lab has also applied them to the development of biofuels and, of course, the study of cancer biology.
Most recently, Rabinowitz has been pushing the frontiers of in vivo isotope tracing, and these efforts have significantly advanced the understanding of metabolism. Application of these methods led his group to discover, for example, that lactate, long considered merely a metabolic waste product, is in fact one of the most important circulating biological fuels.
In the field of cancer metabolism, the Rabinowitz lab contributed to the discovery of nutrient uptake via micropinocytosis and of the oncometabolite 2-hydroxyglutarate. Inhibitors of the enzyme that produces 2-hydroxyglutarate, IDH1, are now important anticancer drugs.
Rabinowitz has also focused extensively on the metabolism of two important anabolic cofactors, NADPH and folate. His lab has dissected compensatory mechanisms that render both NADPH and folate metabolism robust and is working to rewire these pathways to treat cancer. To this end, the lab made small molecule inhibitors of the enzymes SHMT and G6PD, which are moving forward as potential cancer therapeutics.
Currently, Rabinowitz is particularly excited by the prospect of quantitatively investigating the ties between diet and metabolism, including the metabolism of tumors and immune cells. His lab has recently found that the ketogenic diet synergizes in mice with classical chemotherapeutics for pancreatic cancer and is now testing this combination clinically. These studies promise to open new approaches to the prevention and treatment of cancer.