OMB No. 0925-0001 and 0925-0002 (Rev. 09/17 Approved Through 03/31/2020)

NAME: Kapur, Payal

eRA COMMONS USER NAME (credential, e.g., agency login): P1kapu

POSITION TITLE: Associate Professor, Pathology

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

A. Personal Statement

As the Group Leader of Genitourinary Pathology at UT Southwestern Medical Center, the Co-Leader of the Kidney Cancer Program at Simmons Cancer Center, the former Medical Director of Surgical Pathology at Parkland Hospital, and the Co-Director of the Simmons Cancer Center tissue repository I have extensive experience in both prostate and renal cancer. In addition, I serve as the pathologist for our urologic cancer tumor board. My research interests include adult genitourinary cancers and in particular the identification of biomarkers. I’m interested in the development of diagnostic tests with prognostic or predictive value. I have extensive experience in developing immunohistochemistry (IHC) tests, and of greatest relevance to the field of kidney cancer. I have a productive collaboration with Drs. Hsieh and Zheng with several funding and publications. 

1. Wu, K., Gore, C., Yang, L., Fazil, L., Gleave M., Pong, R.C., Xiao, G., Zhang, L.L., Yun, E.J., Tseng, S.F., Kapur, P., He, D.,Hsieh, J.T. (2012) Slug, a unique androgen-regulated transcription factor, coordinates androgen receptor to facilitate castration resistance in prostate cancer. Mol. Endo. 2012 Sep 26:1496-1507. PMID: 22745193
2. Kapur P, Peña-Llopis S, Christie A, Zhrebker L, Pavía-Jiménez A, Rathmell WK, Xie XJ, Brugarolas J. Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation. Lancet Oncol. 2013 Feb;14(2):159-67. PubMed PMID: 23333114. 
3. Wu, K., Xie, D., Liu, J., Tseng, S.F., Gore, C., Nig. Z., Sharifi, N., Fazil, L., Gleave M., Kapur, P., Xiao, G., Wang, M., Sun, X., ÖZ, O.K., Alexandrakis, G.,Yang, C.R., Hsieh, C-L., Wu, H-S., He, D.,Hsieh, J.T. (2014) The role of DAB2IP in  androgen receptor activation during prostate cancer progression. Oncogene 2014 Apr 33:1954-196 PMID: 23604126
4. Yu, M., Zhou, J., Du, B., Ning, X., Authement, C., Gandee, L., Kapur, P., Hsieh, J.T., Zheng, J. Noninvasive staging of kidney dysfunction enabled by renal clearable luminescent gold nanoparticles nanofluorophores. Angewandte Chemie, 2016 Feb 18;55(8):2787-91. PubMed PMID:26800513.

B. Positions and Honors

Positions and Employment

1997-2000                  Resident in Pathology, Delhi University, Delhi, India

2001-2002            Research Technician, Children’s Medical Center, Dallas TX

2002-2006                  Resident in Pathology, UT Southwestern Medical Center, Dallas, TX

2006-2012                  Assistant Professor, Pathology, UT Southwestern Medical Center, Dallas, TX

2012-                           Associate Professor, Pathology, UT Southwestern Medical Center, Dallas, TX

2012-                           Associate Professor, Urology, UT Southwestern Medical Center, Dallas, TX

Other Experience and Professional Memberships

2007-2013                   Director of Anatomical Pathology Guest Speaker Seminar Series, UTSW

2007-2013                   Director of Philip O’Brien Montgomery Visiting Lectureship Seminar, UTSW

2008-2013                   Co-director of UT Southwestern Tissue Resource (UTSTR), UTSW

2010-2013                   Assistant Director of Anatomic Pathology Resident Education, UTSW

2011-2015                   Ambassador to United Sates and Canadian Academy of Pathology, UTSW

2013 -                          Group Leader, Genitourinary Pathology, UTSW

2013-2015                  Medical Director, PHHS

2014-                           Co-Leader, Kidney Cancer Program, Simmons Cancer Center

Honors

1992             National Scholarship Talent Search Award, Directorate of Education, India

2000             Dr. RP Mathur Memorial Award, Maulana Azad Medical College, Delhi University, India

2002             Gordon L. Vawter, platform presentation Award, Society for Pediatric Pathology

2004             Resident’s Case Presentation Award, Society for Pediatric Pathology

2006             Teaching Award, Pathology Sophomore Curriculum, UTSW 

2007             Second place winner, Case Study Competition, Labmedicine

2010             Vernie A. Stembridge, M.D. Resident Teaching Award, UTSW

2011             Vernie A. Stembridge, M.D. Resident Teaching Award, UTSW

C. Contribution to Science

1. I recently developed IHC assays against two of the 3 most important tumor suppressor proteins, BAP1 and PBRM1. Following on our discovery that BAP1 is inactivated, largely by mutation in 15% of RCC (Pena-Llopis et al., Nat Genet 2012); I developed a highly specific IHC test for BAP1, which I validated in a CLIA laboratory (Kapur et al., J Urol 2014). Using this test, I have been able to determine that BAP1 loss is associated with high Fuhrman grade and mTORC1 activation in ccRCC (Kapur et al., Lancet Onc 2013). Furthermore, I performed BAP1 IHC on the Mayo registry cohort of ~1,400 patients, which led us to find that BAP1 is an independent predictor of survival in patients with localized kidney cancer (Joseph and Kapur, Cancer 2014). I have also developed an IHC test for PBRM1, a second tumor suppressor protein that is lost in ~50% of ccRCC. Using both of these tests, I determined that BAP1 and PBRM1 loss tend to be mutually exclusive (Kapur and Joseph, submitted). Interestingly, I found that the few tumors with simultaneous loss of both proteins have a unique morphology and tend to be rhabdoid (Pena-Llopis et al., Nat Genet 2012). This work established the foundation for the first integrated molecular genetic and pathologic classification of renal cancer.
   1. 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. BAP1 loss defines a new class of renal cell carcinom Nat Genet. 2012 Jun 10;44(7):751-9. PubMed PMID: 22683710; PubMed Central PMCID: PMC3788680. 
   2. Kapur P, Peña-Llopis S, Christie A, Zhrebker L, Pavía-Jiménez A, Rathmell WK, Xie XJ, Brugarolas J. Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation. Lancet Oncol. 2013 Feb;14(2):159-67. PubMed PMID: 23333114.
   3. Joseph RW, Kapur P, Serie DJ, Eckel-Passow JE, Parasramka M, Ho T, Cheville JC, Frenkel E, Rakheja D, Brugarolas J, Parker A. Loss of BAP1 protein expression is an independent marker of poor prognosis in patients with low-risk clear cell renal cell carcinoma. Cancer. 2014 Apr 1;120(7):1059-67. PubMed PMID: 24382589; PubMed Central PMCID: PMC4075029. 
   4. Ho TH, Kapur P, Joseph RW, Serie DJ, Eckel-Passow JE, Parasramka M, Cheville JC, Wu KJ, Frenkel E, Rakheja D, Stefanius K, Brugarolas J, Parker AS. Loss of PBRM1 and BAP1 expression is less common in non-clear cell renal cell carcinoma than in clear cell renal cell carcinoma. Urol Oncol. 2015 Jan;33(1):23.e9-14. PubMed PMID: 25465300; PubMed Central PMCID: PMC4274200. 
2. We have recently published our data on the first genetically-engineered mouse model of ccRCC (Wang et al., PNAS 2014). An important limitation of the field for many years is the lack of a genetically engineered mouse model (GEMM) of ccRCC reproducing frequent genetic events. Despite the discovery of the VHL gene in 1993, such a model doesn’t exist. We generated mice that were Six2-Cre;VhlF/F;Bap1F/+ and found that these mice developed a spectrum of pre-neoplastic cysts and RCC. These lesions were not found in Six2Cre;VhlF/F and Six2Cre;Bap1F/+ (or younger Six2Cre;Bap1F/F) control mice. Carbonic anhydrase IX (CAIX), a HIF-target and a classic marker of ccRCC, had a membranous staining pattern in cysts and neoplastic nodules. In addition, we observed an increase in phosphorylated S6 ribosomal protein (pS6) staining in the neoplastic nodules. These data unequivocally show that, as we had hypothesized, Vhl and Bap1 cooperate in ccRCC development.
   1. 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. Bap1 is essential for kidney function and cooperates with Vhl in renal tumorigenesis. Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16538-43. PubMed PMID: 25359211; PubMed Central PMCID: PMC4246264. 
3. Using DNA and RNA samples from our tissue bank, we have successfully collaborated with Genetech in publishing the first comprehensive genomic analysis comparing renal oncocytoma and different subtypes of non-clear-cell RCC (nccRCC) including papillary RCC (pRCC), chromophobe RCC (chRCC), translocation RCC and unclassified RCC (Durinck et al. Nat Genet 2015). This study of 167 tumors significantly extends the findings from the TCGA on 66 chRCC. We found many novel mutations that may be implicated in nccRCC pathogenesis and a 5-gene set signature that distinguishes the nccRCC subtypes. The finding that pRCC tumors have more mutations than ccRCC tumors and consequently may have more neoantigens may be important in the development of immunotherapies. Our assessment of morphology and in situ hybridization analyses helped determine that the definition of translocation RCCs needs to be expanded to include novel translocations (involving, for example, MITF) and other genetic changes (such as amplification). Our discovery that eosinophilic chRCC lacks characteristic DNA copy number alterations will facilitate clinical recognition of this unique subtype. 
   1. 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. Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes. Nat Genet. 2015 Jan;47(1):13-21. PubMed PMID: 25401301. 
4. In addition, I have collaborated with many investigators from various institutions on projects involving optimization, validation, and evaluation of novel IHC markers, tissue microarray construction, and providing expert morphologic opinion on both human and mouse tissue. We are uniquely poised to investigate such clinically relevant questions especially in RCC for the following reasons: 1) a large repository of frozen and paraffin embedded RCC tumors with exome/gene sequencing and Western blot data (this allows us to optimize IHC protocols by providing optimal controls); 2) state-of-the-art tumorgraft models of RCC that can serve to test molecularly targeted therapies; 3) a fully equipped histology and immunohistochemistry laboratory with expertise in development and standardization of IHC assays of new antibodies; 4) the exceptional multidisciplinary camaraderie in the Kidney Cancer Program www.utsouthwestern.edu/kidneycancer.
   1. Chang KH, Li R, Kuri B, Lotan Y, Roehrborn CG, Liu J, Vessella R, Nelson PS, Kapur P, Guo X, Mirzaei H, Auchus RJ, Sharifi N. A gain-of-function mutation in DHT synthesis in castration-resistant prostate cancer. Cell. 2013 Aug 29;154(5):1074-84. PubMed PMID: 23993097; PubMed Central PMCID: PMC3931012. 
   2. Wang S, Kollipara RK, Srivastava N, Li R, Ravindranathan P, Hernandez E, Freeman E, Humphries CG, Kapur P, Lotan Y, Fazli L, Gleave ME, Plymate SR, Raj GV, Hsieh JT, Kittler R. Ablation of the oncogenic transcription factor ERG by deubiquitinase inhibition in prostate cancer. Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4251-6. PubMed PMID: 24591637; PubMed Central PMCID: PMC3964108. 
   3. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014 Mar 20;507(7492):315-22. PubMed PMID: 24476821; PubMed Central PMCID: PMC3962515. 
   4. Haddad AQ, Kapur P, Singla N, Raman JD, Then MT, Nuhn P, Buchner A, Bastian P, Seitz C, Shariat SF, Bensalah K, Rioux-Leclercq N, Sagalowsky A, Lotan Y, Margulis V. Validation of mammalian target of rapamycin biomarker panel in patients with clear cell renal cell carcinoma. Cancer. 2015 Jan 1;121(1):43-50. PubMed PMID: 25186283.

Complete List of Published Work in My Bibliography:
http://www.ncbi.nlm.nih.gov/myncbi/payal.kapur.1/bibliography/48096789/public/?sort=date&direction=ascending

D. Additional Information: Research Support and/or Scholastic Performance

Ongoing Research Support

RP180192 (PI: Brugarolas)                                                                03/01/2018-02/28/2021           

CPRIT                                                                                                                                     

Dissecting the interplay between BAP1 and PBRM1 in renal cancer

Goal 1: Molecular analysis of BAP1-PBRM1 double-mutant tumors

Goal 2: Dissecting the interplay between Bap1 and Pbrm1 through gene editing and combined targeting in the mouse

Role: Co-I

5R01CA154475-05 (PI: Pedrosa)                                          09/15/2011-07/30/2018           

NIH-NCI                                                                                                                                  

Non-Invasive physiologic predictors of aggressiveness in renal cell

Goal: To identify vascular and diffusion MRI measures in RCC in vivo that correlate to spatially co-registered molecular alterations promoting angiogenesis and hypoxia and predict aggressive behavior.

Role: Co-PI

PC150136 (PI: Hsieh)                                                                                    09/30/2016-09/29/2019                                                           

An association of unique microRNA turnover machinery with prostate cancer progression

Goals: Overall goal is to characterize the role of IFIT-5 in microRNA turnover.

Role: Collaborator

1P50 CA196516-01A1  (PI: Brugarolas)                                07/01/2016-06/30/2021

UTSW SPORE in Kidney Cancer (Project 1) 

Goals/Aims: 1)  to identify a biomarker of HIF-2 dependency in ccRCC, 2) to anticipate mechanisms of acquired resistance to HIF2-I, and 3) to evaluate multiparametric MR imaging as a pharmacodynamic biomarker in a first-in-human phase I clinical trial of this first-in-class HIF2-I in metastatic ccRCC patients.

PC150152P1; (PI: Hsieh)                                                                               08/01/2016-07/31/2019                                                                       

Epigenetic machinery regulates alternative splicing of androgen receptor (AR) gene in castration-resistant prostate cancer (CRPC)

Goals: Overall goal is to explore combination KDM4B inhibitor with AR inhibitor to synergize the therapeutic effect of CRPC.

Role: Collaborator

RP160440 (PI: Brugarolas)                                                               03/01/2016-02/28/2019                        

Targeting the undruggable: a first-in-class inhibitor of the HIF-2 transcription factor

Goal:  To identify prognostic and predictive biomarkers of renal cell carcinoma, expand the repertoire of renal cell carcinoma patients that may benefit from HIF2-I, and pave the way for second generation inhibitors.

Role: Co-PI

RFA R-16-IIRA-1  (PI: Carroll)                                                           03/01/2016-02/28/2019                         

The role of the Lats kinases

Goal:  To provide valuable insight into the molecular nature of sarcomatoid renal cell carcinomas (sRCCs) and   

also provide us with potential therapeutic targets to pursue in treating sRCC.  

Role: Co-I

Completed Research Support

W81XWH-12-1-0337-03 (PI: Hsieh)                                      09/01/2012-08/31/2017

Molecular innovations towards theranostics of aggressive prostate

A DAB2IP-based theranostic agent can be realized to prevent the early onset of prostate cancer metastasis or delay the progression of metastasis. The objective of this application is to generate a new class of dendrimer-based theranostic agents for aggressive prostate cancer.

Role: Collaborator

5R01CA159144-05 (PI: Hsieh)                                                          09/21/2011-07/31/2017           

Targeting aggressive prostate cancer with novel theranostic nanomedicine 

To generate new molecular medicine with specific mechanism of action using a novel drug delivery platform with cancer specific targeting. The outcome will provide new therapeutic regimen for prostate cancer therapy.

Role: Collaborator

OTD-1009260 (PI: Kapur)                                                                              04/05/2016-04/05/2017

PD-L1 in Clear Cell Renal Cell Carcinoma

To evaluate the prevalence and role of PD-L1 and CD8 expression in High Risk Adjuvant ccRCC

Role: PI

W81XWH-13-2-0093-02, University of Washington/DOD Subcontract                                09/30/2013-09/26/2016

Raj, G (PI) 

Targeting the Aberrant Androgen Receptor in Advanced Treatment Resistant Prostate Cancer

To develop novel therapies targeted against the full length and splice variant forms of the androgen receptor in enzalutamide-resistant prostate cancer.

Role: Co-Investigator

OTD-104476-02, Janssen Research & Development LLC                                                               03/20/2013-08/31/2016

Raj, G (PI) 

Targeted Disruption of androgen receptor & cofactors

The goal of this project is to explore the role of AR and its cofactors in prostate cancer

Role: Co-Investigator

RP130603-03, Cancer Prevention & Research Institute of Texas                                        06/01/2013-05/31/2016

Brugarolas, J (PI) 

Evaluation of the role of the BAP1 tumor suppressor gene in renal cancer

The goal of this study is to harness a state of the art tumorgraft model for the evaluation the role of newly discovered mutations in renal cancer and the development of pharmacodynamic markers.

Role: Co-Investigator

W81XWH-12-1-0288-03, U.S. Department of Defense                                                                                 09/30/2012-09/29/2015

Raj, G (PI)       

Targeting Ligand-Dependent and Ligand-Independent Androgen Receptor Signaling in Prostate Cancer

Role: Co-Investigator

5 P30 CA142543-02, NIH      (Willson-PI)                                                                                                                             08/03/2010-07/31/2015                                    

Cancer Center Support Grant

This project supports the Harold C. Simmons Cancer Center at the University of Texas Southwestern Medical Center.  

1R01CA138662-01A2, NCI/NIH/UTA(Liu) (Cadeddu-PI)                                                                 06/01/2010-05/31/2013                                  

Title: Transrectal Imaging of Prostate Cancer Using a Globally Convergent Method

To develop a novel globally convergent method in combination with a transrectal, multi-channel optical imaging system that can be used in vivo for transrectal detection and diagnosis of prostate cancer in humans, to distinguish prostate cancer from benign prostatic parenchyma.

Role: Collaborator