Implicated TSC1 as a tumor suppressor in sporadic ccRCC and putative predictor of mTORC1 inhibitor responsiveness (Kucejova et al., Mol Can Res, 2011).
Identified a novel tumor suppressor gene implicated in 15% of ccRCC (Pena-Llopis et al., Nat Genet, 2012).
Laid the foundation for the first molecular genetic classification of sporadic renal cancer (Kapur et al., Lancet Oncology, 2013).
Discovered a new renal cancer familial syndrome resulting from germline mutations in the BAP1 gene (Farley et al., Mol Can Res, in press).
Established that REDD1 functions in a negative feedback loop linking the two dominant pathways in RCC (Kucejova et al., Mol Can Res, 2011).
Solved the crystal structure of REDD1 (Vega-Rubin de Celis et al., Biochem, 2010).
Determined that mTORC1 regulation by hypoxia is tissue-specific and operates through REDD1-dependent and -independent pathways (Wolff et al., Mol Cell Biol, 2011).
Established that Hif is sufficient to block mitochondrial respiration in vivo (Kucejova et al., Oncogene, 2011).
Discovered that the master regulator of the lysosome, the TFEB transcription factor, is regulated by mTORC1 (Pena-Llopis et al., EMBO J, 2011).
Completed a screen of a chemical library containing 200,000 compounds and identified several lead compounds with selectivity against VHL-deficient cells.
Created a state-of-the-art animal model of RCC using tumor samples from patients (Sivanand et al., Science Translational Medicine, 2012). Determined that when implanted in mice, the tumors recapitulate:
Developed a biomarker assay for BAP1, a protein that is inactivated in 15% of ccRCCs (Pena-Llopis et al., Nat Genet, 2012).
Completed a study evaluating a panel of circulating proteins as potential renal cancer biomarkers.
Opened investigator-initiated clinical trial (NCT00831480) to identify determinants of acquired resistance to mTORC1 inhibitors clinically.
First evaluation of a glycolysis inhibitor against a tumor with a mutation rendering it deficient in a TCA cycle enzyme (Yamasaki et al., Nat Rev Urol, 2011).
Genetically-driven life-saving treatment of a patient with a rare cancer type, an epithelioid angiomyolipoma, for which there were no proven treatments (Wolff et al., J Clin Oncol, 2010).
Reported the first patient with RCC treated with the mTORC1 inhibitor sirolimus (Brugarolas et al., J Clin Oncol, 2008).