Implicated TSC1 as a tumor suppressor in sporadic renal cancer and as potential predictor of tumor responsiveness to mTORC1 inhibitors (Kucejova et al., Mol Can Res, 2011).

Identified a novel tumor suppressor gene (BAP1) that is mutated in 15% of sporadic clear cell renal cancers (Pena-Llopis et al., Nat Genet, 2012).

Determined that mutations in BAP1 and PBRM1 are mutually exclusive and associated with different prognosis establishing thereby the foundation for the first molecular genetic classification of sporadic renal cancer (Pena-Llopis et al., Nat Genet, 2012 & Kapur et al., Lancet Oncology, 2013).

Discovered a new familial kidney cancer syndrome resulting from germline mutations in the BAP1 gene (Farley et al., Mol Can Res, 2013).

Unraveled positive and negative interactions among tumor suppressor genes on 3p (Pena-Llopis et al., Can Res, 2013).

Completed the first integrated genomic study of non-clear-cell tumors (Durinck et al., Nat Genet, 2015).

Through the identification of resistance mutations, established HIF-2 as the first dependency of renal cell carcinoma (Courtney et al., Clin Cancer Res, 2020).

Identified systemic approach for understanding the molecular biology of a novel oncocytic tumor. (Kapur et al., Mod Path, 2020)

Established that REDD1 functions in a negative feedback loop linking the two dominant pathways in renal cancer (VHL/HIF and mTORC1) (Kucejova et al., Mol Can Res, 2011).

Provided atomic level insight on the REDD1 protein and its mechanism of action (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 for the first time that Hif activation 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).

Identified a novel adaptor protein of the PDGF/VEGF receptor orthologue in flies and provided insight into the determinants of sensitivity to sunitinib (Tran et al., Mol Cell Biol, 2013).

Validated HIF-2 as a target in ccRCC and demonstrated that ccRCC can be subclassified based on their dependency on HIF-2 into HIF-2-dependent and -independent tumors (Chen et al., Nature, 2016).

Reported additional mechanism of TFEB regulation by mTORC1 (Vega-Rubin-de-Celis et al., Autophagy, 2017).

Leveraging vascular tumor invasion, determined RCC invasion involves the transient activation of abnormal cell fate program and invasion not always driven by most aggressive cells. (Malladi et al., Nat Comm, 2021)

Novel high-content screening strategy identifies homoharringtonine, a small molecule FDA-approved for CML, as a drug synthetic lethal with VHL loss in ccRCC (Wolff et al., Oncotarget, 2015).

Completed a screen of a chemical library containing 200,000 compounds and identified several lead compounds with selectivity against VHL-deficient kidney cancer cells.

Validated first-in-class HIF-2 inhibitors (PT2385/PT2399), showing on-target activity in preclinical models and in the clinic (Chen et al., Nature, 2016; Courtney et al., J Clin Oncol, 2018; Courtney et al., Clin Cancer Res, 2020).

Created the first animal model of renal cancer (Sivanand et al., Science Translational Medicine, 2012) recapitulating:

Histology

Gene expression

Mutations

Treatment responsiveness

Developed a protocol for the utilization of renal cancer tumorgraft models for preclinical drug testing (Pavia-Jimenez et al., Nat Protoc, 2014).

Created the first genetically-engineered mouse model of ccRCC reproducing the genetics of the disease (Wang and Gu et al., PNAS, 2014).

Through the generation of mouse models, we demonstrated that BAP1 and PBRM1 function as tumor suppressors in ccRCC and are determinants of grade (Gu et al., Cancer Discovery, 2017).

Developed comprehensive tumorgraft platform closely mirroring human tumors that surpasses current conventional models in order to advance precision medicine. (Elias et al., Cell Rep, 2021)

Developed a biomarker assay for BAP1 that is being used in clinical practice (Pena-Llopis et al., Nat Genet, 2012 and Kapur et al., J Urol, 2014).

Determined that BAP1 is an independent predictor of ccRCC progression (Joseph et al., Cancer, 2014).

Determined that ccRCC can be divided into 4 molecular subtypes with different outcomes in patients and developed tests that can be applied to the clinic. (Joseph et al., J Urol, 2016).

Developed an experimental system to dissect determinants of sensitivity and resistance to inhibitors of angiogenesis using patient tumors co-cultured with endothelial or other cells (Tran et al., MCB 2016).

Obtained a patent (U.S. Patent No. 15/761,534, “Biomarkers of Response to HIF-2-Alpha Inhibition in Cancer and Methods for the Use Thereof”) for a biomarker of HIF-2 dependency in ccRCC

Reported the first empirical characterization of the tumor microenvironment, leading to the identification of two subtypes – inflamed and uninflamed (Wang et al., Cancer Discov, 2018). 

Developed a radiology test using PET to evaluate and monitor PD-L1 expression in tumors (Vento et al., J Immunother Cancer, 2019).

Determined that metastatic destination can be predictive of response to systemic therapy (Singla et al., JCI Inisight, 2020).

Developed the first ontology of ccRCC and morphological evolutionary model (Cai et al., eBioMedicine, 2020).

Designed an algorithm to predict response to immunotherapy (Lu et al., Sci Immunol, 2020).

TP53 or SMARCA4 mutations as determinants of faster progression on active surveillance. (Torras et al., Eur Urol , 2021)

Identified correlation between immunotherapy side effect and improved response. (Patel et al., J Immunother Cancer, 2020)

Developed an integrated molecular genetic and morphologic model for RCC tumor progression with prognostic and therapeutic implications. (Kapur et al., Kidney Cancer J, 2020)

Investigator-initiated clinical trial (NCT00831480) to determine the feasibility of everolimus preop in patients with metastatic RCC that can serve to identify determinants of acquired resistance to mTORC1 inhibitors clinically.

Investigator-initiated clinical trial (NCT01896271) to explore whether stereotactic ablative body radiation therapy synergizes with high-dose IL2 and increases the rates of complete durable responses.

First-in-class, first-in-human, phase 1 trial of PT2385, a potent and specific HIF-2 inhibitor. (NCT02293980)

Investigator-initiated clinical trial to assess the role of SBRT in oligometastatic RCC. (NCT02956798)

First clinical trial to evaluate PD-L1 with molecular imaging using PET in RCC. (NCT04006522)

First-in-class, first-in-human phase 1 trial of PT2385, a potent and specific HIF-2 inhibitor. (NCT02293980)

Investigator-initiated clinical trial evaluating pioneering SBRT approach for serious complication – IVC tumor thrombus. (NCT02473536)

Investigator-initiated clinical trial to assess the role of SBRT in oligoprogressive RCC. (NCT03686277)

First study to show target depletion and proof of principle of activity with tumor-directed siRNA. (NCT04169711)

First clinical trial to evaluate PD-L1 with molecular imaging using PET in RCC. (NCT04006522)

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).

Effective treatment of progressing brain metastases from papillary renal cancer with supratherapeutic doses of pazopanib (Jacobs et al., J Clin Oncol, 2013).

Developed novel treatment strategy involving stereotactic radiation for the control of renal cell carcinoma invasion into the vena cava (Hannan et al., Cancer Biol Ther, 2015).

Primary lung cancer may be under-diagnosed in kidney cancer (Bowman et al., Clin Genitourin Cancer, 2017).

Hyperprogression followed by a delayed response to nivolumab and SBRT in RCC (Elias et al., Clin Genitourin Cancer, 2018).

Improved outcomes for brain metastases with multidisciplinary approaches involving neurosurgery and radiosurgery (Bowman et al., Clin Genitourin Cancer, 2019; Wardak et al., Clin Genitourin Cancer, 2019).

Stereotactic radiation delays switch in systemic therapy (Zhang et al., Int J Radiat Oncol Biol Phys, 2019).