James Brugarolas, M.D., Ph.D.

Director of the Kidney Cancer Program

Harold C. Simmons Comprehensive Cancer Center

The Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D.

Internal Medicine - Hematology/Oncology
Medical Treatment of Kidney Cancer
Kidney Cancer

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Biography

James Brugarolas, M.D., Ph.D., is a tenured Professor in the Department of Internal Medicine at UT Southwestern Medical Center (UTSW) and a member of its Division of Hematology/Oncology. He holds the Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D.

A practicing physician-scientist specializing in kidney cancer, Dr. Brugarolas is the founding director of the Kidney Cancer Program (KCP) at the Harold C. Simmons Comprehensive Cancer Center. Recognized for its clinical excellence with a Leaders in Clinical Excellence Program Development Award, for its innovation with a finalist Healthcare Innovation Award, and for its research with one of two National Cancer Institute (NCI) Specialized Program of Research Excellence (SPORE) Awards for kidney cancer in the US, the KCP has become a trailblazing program despite its short history. The program is one of a few across the world to have completed the journey from gene discovery to the development of a drug, a first-in-class HIF2 inhibitor, now approved by the FDA.

Dr. Brugarolas joined the UT Southwestern faculty in 2006. Discoveries from the Brugarolas Laboratory have led to the identification of kidney cancer causing genes, established the foundation for the first molecularly-based classification of the most common type of kidney cancer, enabled mouse models reproducing the human disease, established HIF2 as a core dependency, identified drivers of tumor grade, and provided a biological explanation for elusive prognostic factors.

Dr. Brugarolas earned his medical degree at Spain’s Universidad de Navarra before earning a doctoral degree in biology at the Massachusetts Institute of Technology, where he trained with Tyler Jacks, PhD. He completed an internship and residency in internal medicine at Duke University Medical Center and an oncology fellowship at a combined program of Massachusetts General Hospital, Brigham and Women's Hospital, and the Dana-Farber Cancer Institute (DFCI), where he trained in the laboratory of Nobel Laureate, William G. Kaelin, MD.

An active national and international speaker, Dr. Brugarolas serves on the NCI Renal Cancer Task Force and is the chair of the scientific advisory board of the Academy of Kidney Cancer Investigators. He is a member of the American Society of Clinical Oncology, the American Association for Cancer Research, and the American Society for Clinical Investigation.

He has authored groundbreaking research and published in journals such as The New England Journal of Medicine, Nature, Cancer Cell, Nature Genetics, and Proceedings of the National Academy of Sciences.

Education & Training

Other Post Graduate Training - Massachusetts Institute of Technology (1993-1998)
Fellowship - Massachusetts General Hospital, Brigham & Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School (2001-2003), Medical Oncology
Residency - Duke University - Medicine Residency (1999-2001), Internal Medicine
Internship - Duke University - Medicine Internship (1998-1999), Internal Medicine
Graduate School - Massachusetts Institute of Technology (1993-1998)
Medical School - Universidad de Navarra (1987-1993)

Professional Associations & Affiliations

American Society for Clinical Investigation (2013), Member
MIT chapter of Sigma Xi Scientific Research Society of North America (1998), Member
American Society of Clinical Oncology (2006), Member
American Society for Advancement of Science (2006), Member
American Association for Cancer Research (2006), Member

Honors & Awards

D Magazine Best Doctor 2021
Program Development Award – UT Southwestern 2019
Sherry Wigley Crow Endowed Chair in Cancer Research 2017
Elected Member 2013, American Society for Clinical Investigation
Individual Investigator Research Award 2010, Cancer Prevention and Research Institute of Texas
Basil O'Connor Research Award 2007, March of Dimes
Clinical Scientist Development Award 2007, Doris Duke Charitable Foundation
V Scholar Award 2007, The V Foundation for Cancer Research
Claudia Adams Barr Award for Innovative Basic Cancer Research 2003, Dana-Farber Cancer Institute
Young Investigator Award 2004, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School
Virginia Murchison Linthicum Endowed Scholar in Medical Research 2006, UT Southwestern Medical School
Research Scholar 2008, American Cancer Society

Books & Publications

Books
- Research Translation and Personalized Medicine in Renal Cell Carcinoma
  Brugarolas, J. (2012), Springer US
- mTORC1 Signaling and Hypoxia in mTOR Pathway and mTOR Inhibitors in Cancer Therapy
  Brugarolas, J (2010), Humana Press
Publications
- What morphology can teach us about renal cell carcinoma clonal evolution.
  Kapur P, Christie A, Rajaram S, Brugarolas J, Kidney cancer journal : official journal of the Kidney Cancer Association 2020 Sep 18 3 68-76
- BAP1 loss defines a new class of renal cell carcinoma.
  Peña-Llopis S, Vega-Rubín-de-Celis S, Liao A, Leng N, Pavía-Jiménez A, Wang S, Yamasaki T, Zhrebker L, Sivanand S, Spence P, Kinch L, Hambuch T, Jain S, Lotan Y, Margulis V, Sagalowsky AI, Summerour PB, Kabbani W, Wong SW, Grishin N, Laurent M, Xie XJ, Haudenschild CD, Ross MT, Bentley DR, Kapur P, Brugarolas J Nature genetics 2012 Jul 44 7 751-9
- A validated tumorgraft model reveals activity of dovitinib against renal cell carcinoma.
  Sivanand S, Peña-Llopis S, Zhao H, Kucejova B, Spence P, Pavia-Jimenez A, Yamasaki T, McBride DJ, Gillen J, Wolff NC, Morlock L, Lotan Y, Raj GV, Sagalowsky A, Margulis V, Cadeddu JA, Ross MT, Bentley DR, Kabbani W, Xie XJ, Kapur P, Williams NS, Brugarolas J Science translational medicine 2012 Jun 4 137 137ra75
- Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade.
  Gu YF, Cohn S, Christie A, McKenzie T, Wolff NC, Do QN, Madhuranthakam A, Pedrosa I, Wang T, Dey A, Busslinger M, Xie XJ, Hammer RE, McKay RM, Kapur P, Brugarolas J Cancer discovery 2017 May
- Multicenter Validation of Enhancer of Zeste Homolog 2 Expression as an Independent Prognostic Marker in Localized Clear Cell Renal Cell Carcinoma.
  Ho TH, Kapur P, Eckel-Passow JE, Christie A, Joseph RW, Serie DJ, Cheville JC, Thompson RH, Homayoun F, Panwar V, Brugarolas J, Parker AS Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2017 Oct JCO2017733238
- High-throughput simultaneous screen and counterscreen identifies homoharringtonine as synthetic lethal with von Hippel-Lindau loss in renal cell carcinoma.
  Wolff NC, Pavía-Jiménez A, Tcheuyap VT, Alexander S, Vishwanath M, Christie A, Xie XJ, Williams NS, Kapur P, Posner B, McKay RM, Brugarolas J Oncotarget 2015 Jul 6 19 16951-62
- Renal Cell Carcinoma With Pulmonary Metastasis and Metachronous Non-Small Cell Lung Cancer.
  Bowman IA, Pedrosa I, Kapur P, Brugarolas J Clinical genitourinary cancer 2017 Feb
- Phase II Trial of Stereotactic Ablative Radiation for Oligoprogressive Metastatic Kidney Cancer.
  Hannan R, Christensen M, Hammers H, Christie A, Paulman B, Lin D, Garant A, Arafat W, Courtney K, Bowman I, Cole S, Sher D, Ahn C, Choy H, Timmerman R, Brugarolas J, European urology oncology 2021 Dec
- Clear cell renal cell carcinoma subtypes identified by BAP1 and PBRM1 expression.
  Joseph RW, Kapur P, Serie DJ, Parasramka M, Ho TH, Cheville JC, Frenkel E, Parker AS, Brugarolas J The Journal of urology 2015 Aug
- Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI.
  Zhang Y, Udayakumar D, Cai L, Hu Z, Kapur P, Kho EY, Pavía-Jiménez A, Fulkerson M, de Leon AD, Yuan Q, Dimitrov IE, Yokoo T, Ye J, Mitsche MA, Kim H, McDonald JG, Xi Y, Madhuranthakam AJ, Dwivedi DK, Lenkinski RE, Cadeddu JA, Margulis V, Brugarolas J, DeBerardinis RJ, Pedrosa I JCI insight 2017 Aug 2 15
- Improved Survival Outcomes for Kidney Cancer Patients With Brain Metastases.
  Bowman IA, Bent A, Le T, Christie A, Wardak Z, Arriaga Y, Courtney K, Hammers H, Barnett S, Mickey B, Patel T, Whitworth T, Stojadinovic S, Hannan R, Nedzi L, Timmerman R, Brugarolas J, Clinical genitourinary cancer 2019 Apr 17 2 e263-e272
- PD-L1 detection using ⁸⁹Zr-atezolizumab immuno-PET in renal cell carcinoma tumorgrafts from a patient with favorable nivolumab response.
  Vento J, Mulgaonkar A, Woolford L, Nham K, Christie A, Bagrodia A, de Leon AD, Hannan R, Bowman I, McKay RM, Kapur P, Hao G, Sun X, Brugarolas J, Journal for immunotherapy of cancer 2019 Jun 7 1 144
- HIF-2 Complex Dissociation, Target Inhibition, and Acquired Resistance with PT2385, a First-in-Class HIF-2 Inhibitor in Clear Cell Renal Cell Carcinoma Patients.
  Courtney KD, Ma Y, Diaz de Leon A, Christie A, Xie Z, Woolford L, Singla N, Joyce A, Hill H, Madhuranthakam AJ, Yuan Q, Xi Y, Zhang Y, Chang J, Fatunde O, Arriaga Y, Frankel AE, Kalva S, Zhang S, McKenzie T, Reig O, Figlin RA, Rini BI, McKay RM, Kapur P, Wang T, Pedrosa I, Brugarolas J, Clinical cancer research : an official journal of the American Association for Cancer Research 2019 Nov
- Pancreatic tropism of metastatic renal cell carcinoma.
  Singla N, Xie Z, Zhang Z, Gao M, Yousuf Q, Onabolu O, McKenzie T, Tcheuyap VT, Ma Y, Choi J, McKay R, Christie A, Torras OR, Bowman IA, Margulis V, Pedrosa I, Przybycin C, Wang T, Kapur P, Rini B, Brugarolas J, JCI insight 2020 Apr 5 7
- The Evolution of Angiogenic and Inflamed Tumors: The Renal Cancer Paradigm.
  Brugarolas J, Rajaram S, Christie A, Kapur P, Cancer cell 2020 Dec 38 6 771-773
- A renal cell carcinoma tumorgraft platform to advance precision medicine.
  Elias R, Tcheuyap VT, Kaushik AK, Singla N, Gao M, Reig Torras O, Christie A, Mulgaonkar A, Woolford L, Stevens C, Kettimuthu KP, Pavia-Jimenez A, Boroughs LK, Joyce A, Dakanali M, Notgrass H, Margulis V, Cadeddu JA, Pedrosa I, Williams NS, Sun X, DeBerardinis RJ, Öz OK, Zhong H, Seshagiri S, Modrusan Z, Cantarel BL, Kapur P, Brugarolas J, Cell reports 2021 Nov 37 8 110055
- Germline and sporadic mTOR pathway mutations in low-grade oncocytic tumor of the kidney.
  Kapur P, Gao M, Zhong H, Chintalapati S, Mitui M, Barnes SD, Zhou Q, Miyata J, Carrillo D, Malladi VS, Rakheja D, Pedrosa I, Xu L, Kinch L, Brugarolas J, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2021 Sep
- Stereotactic Ablative Radiation for Systemic Therapy-naive Oligometastatic Kidney Cancer.
  Hannan R, Christensen M, Christie A, Garant A, Pedrosa I, Robles L, Mannala S, Wang C, Hammers H, Arafat W, Courtney K, Bowman IA, Sher D, Ahn C, Cole S, Choy H, Timmerman R, Brugarolas J, European urology oncology 2022 Aug
- HIF2 inactivation and tumor suppression with a tumor-directed RNA-silencing drug in mice and humans.
  Ma Y, Joyce A, Brandenburg O, Saatchi F, Stevens C, Tcheuyap VT, Christie A, Do Q, Fatunde O, Macchiaroli A, Wong SC, Woolford L, Yousuf Q, Miyata J, Carrillo D, Onabolu O, McKenzie T, Mishra A, Hardy T, He W, Li D, Ivanishev A, Zhang Q, Pedrosa I, Kapur P, Schluep T, Kanner SB, Hamilton J, Brugarolas J, Clinical cancer research : an official journal of the American Association for Cancer Research 2022 Oct
- Regulation of TFEB and V-ATPases by mTORC1.
  Peña-Llopis S, Vega-Rubin-de-Celis S, Schwartz JC, Wolff NC, Tran TA, Zou L, Xie XJ, Corey DR, Brugarolas J The EMBO journal 2011 Aug 30 16 3242-58
- Interplay between pVHL and mTORC1 pathways in clear-cell renal cell carcinoma.
  Kucejova B, Peña-Llopis S, Yamasaki T, Sivanand S, Tran TA, Alexander S, Wolff NC, Lotan Y, Xie XJ, Kabbani W, Kapur P, Brugarolas J Molecular cancer research : MCR 2011 Sep 9 9 1255-65
- Cooperation and Antagonism among Cancer Genes: The Renal Cancer Paradigm.
  Peña-Llopis S, Christie A, Xie XJ, Brugarolas J Cancer research 2013 Jul 73 14 4173-9
- Germline BAP1 mutation predisposes to familial clear-cell renal cell carcinoma.
  Farley MN, Schmidt LS, Mester JL, Pena-Llopis S, Pavia-Jimenez A, Christie A, Vocke CD, Ricketts CJ, Peterson J, Middelton L, Kinch L, Grishin N, Merino MJ, Metwalli AR, Xing C, Xie XJ, Dahia PL, Eng C, Linehan WM, Brugarolas J Molecular cancer research : MCR 2013 May
- Bap1 is essential for kidney function and cooperates with Vhl in renal tumorigenesis.
  Wang SS, Gu YF, Wolff N, Stefanius K, Christie A, Dey A, Hammer RE, Xie XJ, Rakheja D, Pedrosa I, Carroll T, McKay RM, Kapur P, Brugarolas J Proceedings of the National Academy of Sciences of the United States of America 2014 Nov 111 46 16538-43
- Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes.
  Durinck S, Stawiski EW, Pavía-Jiménez A, Modrusan Z, Kapur P, Jaiswal BS, Zhang N, Toffessi-Tcheuyap V, Nguyen TT, Pahuja KB, Chen YJ, Saleem S, Chaudhuri S, Heldens S, Jackson M, Peña-Llopis S, Guillory J, Toy K, Ha C, Harris CJ, Holloman E, Hill HM, Stinson J, Rivers CS, Janakiraman V, Wang W, Kinch LN, Grishin NV, Haverty PM, Chow B, Gehring JS, Reeder J, Pau G, Wu TD, Margulis V, Lotan Y, Sagalowsky A, Pedrosa I, de Sauvage FJ, Brugarolas J, Seshagiri S Nature genetics 2014 Nov
- Stereotactic Radiation Therapy of Renal Cancer Inferior Vena Cava Tumor Thrombus.
  Hannan R, Margulis V, Chun SG, Cannon N, Kim DW, Abdulrahman RE, Sagalowsky A, Pedrosa I, Choy H, Brugarolas JB, Timmerman RD Cancer biology & therapy 2015 Mar 0
- Targeting Renal Cell Carcinoma with a HIF-2 antagonist.
  Chen W, Hill H, Christie A, Kim MS, Holloman E, Pavia-Jimenez A, Homayoun F, Ma Y, Patel N, Yell P, Hao G, Yousuf Q, Joyce A, Pedrosa I, Geiger H, Zhang H, Chang J, Gardner KH, Bruick RK, Reeves C, Hwang TH, Courtney K, Frenkel E, Sun X, Zojwalla N, Wong T, Rizzi JP, Wallace EM, Josey JA, Xie Y, Xie XJ, Kapur P, McKay RM, Brugarolas J Nature 2016 Sep
- Hypoxia-inducible factor-1a activates insig-2 transcription for degradation of HMG CoA reductase in the liver.
  Hwang S, Nguyen AD, Jo Y, Engelking LJ, Brugarolas J, DeBose-Boyd RA The Journal of biological chemistry 2017 Apr
- BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma: tumor heterogeneity and concordance with paired primary tumor.
  Eckel-Passow JE, Serie DJ, Cheville JC, Ho TH, Kapur P, Brugarolas J, Thompson RH, Leibovich BC, Kwon ED, Joseph RW, Parker AS BMC urology 2017 Mar 17 1 19
- An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors.
  Wang T, Lu R, Kapur P, Jaiswal BS, Hannan R, Zhang Z, Pedrosa I, Luke JJ, Zhang H, Goldstein LD, Yousuf Q, Gu YF, McKenzie T, Joyce A, Kim MS, Wang X, Luo D, Onabolu O, Stevens C, Xie Z, Chen M, Filatenkov A, Torrealba J, Luo X, Guo W, He J, Stawiski E, Modrusan Z, Durinck S, Seshagiri S, Brugarolas J Cancer discovery 2018 Jun
- Succination of Keap1 and activation of Nrf2-dependent antioxidant pathways in FH-deficient papillary renal cell carcinoma type 2.
  Kinch L, Grishin NV, Brugarolas J Cancer cell 2011 Oct 20 4 418-20
- Molecular genetics of clear-cell renal cell carcinoma.
  Brugarolas J Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2014 Jun 32 18 1968-76
- PDGF/VEGF Receptor Inactivation by Sunitinib Results in Tsc1/Tsc2-Dependent Inhibition of TORC1.
  Tran TA, Kinch L, Peña-Llopis S, Kockel L, Grishin N, Jiang H, Brugarolas J Molecular and cellular biology 2013 Jul
- Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma.
  De Velasco G, Xie W, Donskov F, Albiges L, Beuselinck B, Srinivas S, Agarwal N, Lee JL, Brugarolas J, Wood LA, Rha SY, Kollmannsberger C, North S, Kanesvaran R, Rini BI, Broom R, Yamamoto H, Kaymakcalan MD, Heng DYC, Choueiri TK Clinical genitourinary cancer 2017 Jun 15 3 403-410.e2
- Hepatic mTORC1 Opposes Impaired Insulin Action to Control Mitochondrial Metabolism in Obesity.
  Kucejova B, Duarte J, Satapati S, Fu X, Ilkayeva O, Newgard CB, Brugarolas J, Burgess SC Cell reports 2016 Jun
- Exploring a glycolytic inhibitor for the treatment of an FH-deficient type-2 papillary RCC.
  Yamasaki T, Tran TA, Oz OK, Raj GV, Schwarz RE, Deberardinis RJ, Zhang X, Brugarolas J Nature reviews. Urology 2011 Mar 8 3 165-71
- Predictive Biomarkers for Molecularly Targeted Therapies in Renal Cell Carcinoma.
  Brugarolas J Journal of the National Comprehensive Cancer Network : JNCCN 2016 Jul 14 7 925-7
- Multistep regulation of TFEB by MTORC1.
  Vega-Rubin-de-Celis S, Peña-Llopis S, Konda M, Brugarolas J Autophagy 2017 Jan 0
- Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation.
  Kapur P, Peña-Llopis S, Christie A, Zhrebker L, Pavía-Jiménez A, Rathmell WK, Xie XJ, Brugarolas J The lancet oncology 2013 Feb 14 2 159-67
- Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Carcinoma Extracranial Metastases.
  Wang CJ, Christie A, Lin MH, Jung M, Weix D, Huelsmann L, Kuhn K, Meyer J, Desai N, Kim DWN, Pedrosa I, Margulis V, Cadeddu J, Sagalowsky A, Gahan J, Laine A, Xie XJ, Choy H, Brugarolas J, Timmerman R, Hannan R International journal of radiation oncology, biology, physics 2017 May 98 1 91-100

Research

Immunotherapy
Biomarkers
Kidney cancer, renal cell carcinoma (RCC)
Molecular genetics and genomics of cancer
Molecularly targeted therapies
Signaling mechanisms and mechanisms of resistance to targeted agents
Research translation

Clinical Focus

Medical Treatment of Kidney Cancer
Kidney Cancer

Q&A by Dr. Brugarolas

Kidney Cancer