Raj Lab Publications

Prostate Cancer

• Wang S, Gilbreath C, Kollipara RK, Sonavane R, Huo X, Yenerall P, Das A, Ma S, Raj GV, Kittler R. Mithramycin suppresses DNA damage repair via targeting androgen receptor in prostate cancer. Cancer Lett. 2020 Sep 28;488:40-49. doi:10.1016/j.canlet.2020.05.027. Epub 2020 May 30. PMID: 32485222.

  MTM treatment with RT or radiomimetic agents, may present a novel effective therapeutic strategy for patients with high-risk, clinically localized PCa.

• Ramanand SG, Chen Y, Yuan J, Daescu K, Lambros M, Houlahan KE, Carreira S,Yuan W, Baek G, Sharp A, Paschalis A, Kanchwala M, Gao Y, Aslam A, Safdar N, Zhan X, Raj GV, Xing C, Boutros PC, de Bono J, Zhang MQ, Mani RS. The landscape of RNA polymerase II associated chromatin interactions in prostate cancer. J Clin Invest. 2020 Apr 28. pii: 134260. doi:10.1172/JCI134260. [Epub ahead of print] PubMed PMID: 32343676.

  A novel germline-somatic interplay between the PCa risk allele rs684232 and the somatically acquired TMPRSS2-ERG gene fusion as a critical determinant of aberrant transcriptional regulation in PCa.

• Brand LJ, Olson ME, Ravindranathan P, Guo H, Kempema AM, Andrews TE, Chen X,  Raj GV, Harki DA, Dehm SM. EPI-001 is a selective peroxisome proliferator-activated receptor-gamma modulator with inhibitory effects on androgen receptor expression and activity in prostate cancer. 2015 Feb 28;6(6):3811-24. PubMed PMID: 25669987; PubMed Central PMCID: PMC4414155. 

  EPI-001 ihibits AR through a non-LBD mechanism.

• Centenera MM, Raj GV, Knudsen KE, Tilley WD, Butler LM.Ex vivo culture of human prostate tissue and drug development. Nat Rev Urol. 2013 Aug;10(8):483-7. doi: 10.1038/nrurol.2013.126. Epub 2013 Jun 11. Review. PubMed PMID: 23752995.

  Ex vivo culture poised to accelerate translational "hit rate"  for prostate cancer research.

• Chan SC, Selth LA, Li Y, Nyquist MD, Miao L, Bradner JE, Raj GV, Tilley WD, Dehm SM. Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res. 2015 Jul 13;43(12):5880-97. doi: 10.1093/nar/gkv262. Epub 2015 Apr 23. PubMed PMID: 25908785; PubMed Central PMCID: PMC4499120.

  JQ1 resulted in inhibition of AR-V chromatin binding and impaired AR-V driven PCa cell growth in vitro and in vivo.

• Chung PH, Gayed BA, Thoreson GR, Raj GV. Emerging drugs for prostate cancer. Expert Opin Emerg Drugs. 2013 Dec;18(4):533-50. doi: 10.1517/14728214.2013.864635. Review. PubMed PMID: 24274615.

  New medications make it imperative for physicians to keep pace to better serve their patients.

• Clinton TN, Bagrodia A, Lotan Y, Margulis V, Raj GV, Woldu SL. Tissue-based biomarkers in prostate cancer. Expert Rev Precis Med Drug Dev. 2017;2(5):249-260. doi: 10.1080/23808993.2017.1372687. Epub 2017 Sep 5. PubMed PMID: 29226251; PubMed Central PMCID: PMC5722240.

  Tumor heterogeneity may impose a ceiling on the prognostic ability of biomarkers using currently available techniques.

• Clinton TN, Woldu SL, Raj GV. Degarelix versus luteinizing hormone-releasing hormone agonists for the treatment of prostate cancer. Expert Opin Pharmacother. 2017 Jun;18(8):825-832. doi: 10.1080/14656566.2017.1328056. Epub 2017 May 19. Review. PubMed PMID: 28480768.

  Degarelix shows benefits over lutenizing hormone agonists for patients with hormone sensitive prostate cancer.

• Duan L, Rai G, Roggero C, Zhang QJ, Wei Q, Ma SH, Zhou Y, Santoyo J, Martinez ED, Xiao G, Raj GV, Jadhav A, Simeonov A, Maloney DJ, Rizo J, Hsieh JT, Liu ZP. KDM4/JMJD2 Histone Demethylase Inhibitors Block Prostate Tumor Growth by Suppressing the Expression of AR and BMYB-Regulated Genes. Chem Biol. 2015 Sep 17;22(9):1185-96. doi: 10.1016/j.chembiol.2015.08.007. Epub 2015 Sep 10. PubMed PMID: 26364928; PubMed Central PMCID: PMC4578295.

  Our studies suggest a potential mechanism-based therapeutic strategy for PCa and tumors with elevated KDM4B/PLK1 expression.

• Freifeld Y, Xi Y, Passoni N, Woldu S, Hornberger B, Goldberg K, Bagrodia A, Raj G, Margulis V, Cadeddu JA, Lotan Y, Francis F, Pedrosa I, G Roehrborn C, Costa DN. Optimal sampling scheme in men with abnormal multiparametric MRI undergoing MRI-TRUS fusion prostate biopsy. Urol Oncol. 2019 Jan;37(1):57-62. doi: 10.1016/j.urolonc.2018.10.009. Epub 2018 Nov 13. PubMed PMID: 30446460.

  TBx + ipsi-SBx may increase the detection of csPCa while limiting overdiagnosis of indolent cancers.

• Giri VN, Knudsen KE, Kelly WK, Abida W, Andriole GL, Bangma CH, Bekelman JE, Benson MC, Blanco A, Burnett A, Catalona WJ, Cooney KA, Cooperberg M, Crawford DE, Den RB, Dicker AP, Eggener S, Fleshner N, Freedman ML, Hamdy FC, Hoffman-Censits J, Hurwitz MD, Hyatt C, Isaacs WB, Kane CJ, Kantoff P, Karnes RJ, Karsh LI, Klein EA, Lin DW, Loughlin KR, Lu-Yao G, Malkowicz SB, Mann MJ, Mark JR, McCue PA, Miner MM, Morgan T, Moul JW, Myers RE, Nielsen SM, Obeid E, Pavlovich CP, Peiper SC, Penson DF, Petrylak D, Pettaway CA, Pilarski R, Pinto PA, Poage W, Raj GV, Rebbeck TR, Robson ME, Rosenberg MT, Sandler H, Sartor O, Schaeffer E, Schwartz GF, Shahin MS, Shore ND, Shuch B, Soule HR, Tomlins SA, Trabulsi EJ, Uzzo R, Vander Griend DJ, Walsh PC, Weil CJ, Wender R, Gomella LG. Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017. J Clin Oncol. 2018 Feb 1;36(4):414-424. doi: 10.1200/JCO.2017.74.1173. Epub 2017 Dec 13. PubMed PMID: 29236593; PubMed Central PMCID: PMC6075860.

  Future research should focus on developing a working definition of familial PCA for clinical genetic testing

• Grabowska MM, Elliott AD, DeGraff DJ, Anderson PD, Anumanthan G, Yamashita H, Sun Q, Friedman DB, Hachey DL, Yu X, Sheehan JH, Ahn JM, Raj GV, Piston DW, Gronostajski RM, Matusik RJ. NFI transcription factors interact with FOXA1 to regulate prostate-specific gene expression. Mol Endocrinol. 2014 Jun;28(6):949-64. doi: 10.1210/me.2013-1213. Epub 2014 May 6. PubMed PMID: 24801505; PubMed Central PMCID: PMC4042066.

  NFI regulation of FOXA1/AR action is a frequent event, with individual family members playing distinct roles in AR target gene expression.

• Henry GH, Malewska A, Joseph DB, Malladi VS, Lee J, Torrealba J, Mauck RJ, Gahan JC, Raj GV, Roehrborn CG, Hon GC, MacConmara MP, Reese JC, Hutchinson RC, Vezina CM, Strand DW. A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra. Cell Rep. 2018 Dec 18;25(12):3530-3542.e5. doi:10.1016/j.celrep.2018.11.086. PubMed PMID: 30566875; PubMed Central PMCID:PMC6411034.

  New tools can identify cell types enriched in the prostatic urethra and proximal prostatic ducts., isolate, and localize every cell type.

• Henzler C, Li Y, Yang R, McBride T, Ho Y, Sprenger C, Liu G, Coleman I, Lakely B, Li R, Ma S, Landman SR, Kumar V, Hwang TH, Raj GV, Higano CS, Morrissey C, Nelson PS, Plymate SR, Dehm SM. Truncation and constitutive activation of the androgen receptor by diverse genomic rearrangements in prostate cancer. Nat Commun. 2016 Nov 29;7:13668. doi: 10.1038/ncomms13668. PubMed PMID: 27897170; PubMed Central PMCID: PMC5141345.

  AR genomic structural rearrangements are important drivers of persistent AR signalling in CRPC

• Lee TK, Ravindranathan P, Sonavane R, Raj GV, Ahn JM. A Structure-Activity Relationship Study of Bis-Benzamides as Inhibitors of Androgen Receptor-Coactivator Interaction. Molecules. 2019 Jul 31;24(15):2783. doi: 10.3390/molecules24152783. PMID: 31370197; PMCID: PMC6696232.

  Inhibitor 14d exerts its anticancer activity by inhibiting the AR–PELP1 interaction and AR transactivation.
• Ta HQ, Whitworth H, Yin Y, Conaway M, Frierson HF Jr, Campbell MJ, Raj GV, Gioeli D. Discovery of a novel long noncoding RNA overlapping the LCK gene that regulates prostate cancer cell growth. Mol Cancer. 2019 Jun 28;18(1):113. doi: 10.1186/s12943-019-1039-6. PMID: 31253147; PMCID: PMC6598369.

          A novel lncRNA situated within the LCK gene that may serve as an oncogene in PCA.

• Lee CF, Dang A, Hernandez E, Pong RC, Chen B, Sonavane R, Raj G, Kapur P, Lin HY, Wu SR, Ko CJ, Lo UG, Lee HY, Hsieh JT, Lee MS. Activation of sphingosine kinase by lipopolysaccharide promotes prostate cancer cell invasion and metastasis via SphK1/S1PR4/matriptase. Oncogene. 2019 Jul;38(28):5580-5598. doi:10.1038/s41388-019-0833-3. Epub 2019 May 31. PubMed PMID: 31152147.

          Sphingosine kinase signaling underlies LPS-induced matriptase activation and PCa cell invasion.

• Li X, Baek G, Ramanand SG, Sharp A, Gao Y, Yuan W, Welti J, Rodrigues DN, Dolling D, Figueiredo I, Sumanasuriya S, Crespo M, Aslam A, Li R, Yin Y, Mukherjee B, Kanchwala M, Hughes AM, Halsey WS, Chiang CM, Xing C, Raj GV, Burma S, de Bono J, Mani RS. BRD4 Promotes DNA Repair and Mediates the Formation of TMPRSS2-ERG Gene Rearrangements in Prostate Cancer. Cell Rep. 2018 Jan 16;22(3):796-808. doi: 10.1016/j.celrep.2017.12.078. PubMed PMID: 29346775; PubMed Central PMCID: PMC5843368.

          BRD4 is a central player in the repair of DNA DSBs, with significant implications for cancer therapy.

• Liao RS, Ma S, Miao L, Li R, Yin Y, Raj GV. Androgen receptor-mediated non-genomic regulation of prostate cancer cell proliferation. Transl Androl Urol. 2013 Sep;2(3):187-96. doi: 10.3978/j.issn.2223-4683.2013.09.07. Review. PubMed PMID: 26816736; PubMed Central PMCID: PMC4708176.

  Preventing AR nuclear translocation and genomic AR signaling alone may not completely abrogate AR signaling.

• Luo J, Attard G, Balk SP, Bevan C, Burnstein K, Cato L, Cherkasov A, De Bono JS, Dong Y, Gao AC, Gleave M, Heemers H, Kanayama M, Kittler R, Lang JM, Lee RJ, Logothetis CJ, Matusik R, Plymate S, Sawyers CL, Selth LA, Soule H, Tilley W, Weigel NL, Zoubeidi A, Dehm SM, Raj GV. Role of Androgen Receptor Variants in Prostate Cancer: Report from the 2017 Mission Androgen Receptor Variants Meeting. Eur Urol. 2018 May;73(5):715-723. doi: 10.1016/j.eururo.2017.11.038. Epub 2017 Dec 16. PubMed PMID: 29258679; PubMed Central PMCID: PMC5929166.

  Detection of AR variants (eg, AR-V7) identified a patient population with poor outcomes to existing AR-targeting therapies

• Marian CO, Yang L, Zou YS, Gore C, Pong RC, Shay JW, Kabbani W, Hsieh JT, Raj GV. Evidence of epithelial to mesenchymal transition associated with increased tumorigenic potential in an immortalized normal prostate epithelial cell line. 2011 May;71(6):626-36. doi: 10.1002/pros.21278. Epub 2010 Oct 13. PubMed PMID: 20945502.

  Xenograft tumor derived cell line appears to have undergone an epithelial-to-mesenchymal transition (EMT). 

• Miao L, Yang L, Li R, Rodrigues DN, Crespo M, Hsieh JT, Tilley WD, de Bono J,  Selth LA, Raj GV. Disrupting Androgen Receptor Signaling Induces Snail-Mediated Epithelial-Mesenchymal Plasticity in Prostate Cancer. Cancer Res. 2017 Jun 1;77(11):3101-3112. doi: 10.1158/0008-5472.CAN-16-2169. Epub 2017 Mar 16. PubMed  PMID: 28302679.

  De-repression of Snail and induction of EMP is an adaptive response to enzalutamide with implications for therapy resistance.

• Nassar ZD, Aref AT, Miladinovic D, Mah CY, Raj GV, Hoy AJ, Butler LM. Peri-prostatic adipose tissue: the metabolic microenvironment of prostate cancer. BJU Int. 2018 May;121 Suppl 3:9-21. doi: 10.1111/bju.14173. Epub 2018 Mar 26. Review. PubMed PMID: 29460324.

  Peri-prostatic adipose tissue influences PCa pathogenesis and progression

• Paltoglou S, Das R, Townley SL, Hickey TE, Tarulli GA, Coutinho I, Fernandes R, Hanson AR, Denis I, Carroll JS, Dehm SM, Raj GV, Plymate SR, Tilley WD, Selth  LA. Novel Androgen Receptor Coregulator GRHL2 Exerts Both Oncogenic and Antimetastatic Functions in Prostate Cancer. Cancer Res. 2017 Jul 1;77(13):3417-3430. doi: 10.1158/0008-5472.CAN-16-1616. Epub 2017 May 4. PubMed PMID: 28473532; PubMed Central PMCID: PMC5497757.

  GRHL2 enhances AR and maintains epithelial phenotype

• Paschalis A, Sharp A, Welti JC, Neeb A, Raj GV, Luo J, Plymate SR, de Bono JS. Alternative splicing in prostate cancer. Nat Rev Clin Oncol. 2018 Nov;15(11):663-675. doi: 10.1038/s41571-018-0085-0. Review. PubMed PMID: 30135575.

  Spliceosome modulation is a potential therapeutic avenue  against AR-Vs

• Ravindranathan P, Lee TK, Yang L, Centenera MM, Butler L, Tilley WD, Hsieh JT, Ahn JM, Raj GV. Peptidomimetic targeting of critical androgen receptor-coregulator interactions in prostate cancer. Nat Commun. 2013;4:1923. doi: 10.1038/ncomms2912. PubMed PMID: 23715282.

  Using peptidomimetics targeting receptor-coregulator interactions may be a viable therapeutic approach for patients with advanced prostate cancer.

• Schiewer MJ, Goodwin JF, Han S, Brenner JC, Augello MA, Dean JL, Liu F, Planck JL, Ravindranathan P, Chinnaiyan AM, McCue P, Gomella LG, Raj GV, Dicker AP, Brody JR, Pascal JM, Centenera MM, Butler LM, Tilley WD, Feng FY, Knudsen KE.Dual roles of PARP-1 promote cancer growth and progression. Cancer Discov. 2012 Dec;2(12):1134-49. doi: 10.1158/2159-8290.CD-12-0120. Epub 2012 Sep 19. PubMed PMID: 22993403; PubMed Central PMCID: PMC3519969.

  DNA damage repair and transcription factor regulation offer a paradigm shift in PARP-1 function in human malignancy

• Sen A, De Castro I, Defranco DB, Deng FM, Melamed J, Kapur P, Raj GV, Rossi R, Hammes SR. Paxillin mediates extranuclear and intranuclear signaling in prostate cancer proliferation. J Clin Invest. 2012 Jul;122(7):2469-81. doi: 10.1172/JCI62044. Epub 2012 Jun 11. PubMed PMID: 22684108; PubMed Central PMCID:  PMC3386821.

  Paxillin is a potential biomarker for prostate cancer proliferation and a possible therapeutic target for prostate cancer treatment.

• Sen A, O'Malley K, Wang Z, Raj GV, Defranco DB, Hammes SR. Paxillin regulates androgen- and epidermal growth factor-induced MAPK signaling and cell proliferation in prostate cancer cells. J Biol Chem. 2010 Sep 10;285(37):28787-95. doi: 10.1074/jbc.M110.134064. Epub 2010 Jul 13. PubMed PMID: 20628053; PubMed Central PMCID: PMC2937906.

  Paxillin may prove to be a novel diagnostic or therapeutic target in prostate cancer.

• Singla N, Ghandour RA, Raj GV. Investigational luteinizing hormone releasing hormone (LHRH) agonists and other hormonal agents in early stage clinical trials for prostate cancer. Expert Opin Investig Drugs. 2019 Mar;28(3):249-259. doi:10.1080/13543784.2019.1570130. Epub 2019 Jan 28. Review. PubMed PMID: 30649971.

          Deficiencies in the understanding of the mechanisms underlying prostate cancer pathogenesis s preventing hormonal agent success in clinical trials.

• Thoreson GR, Gayed BA, Chung PH, Raj GV. Emerging therapies in castration resistant prostate cancer. Can J Urol. 2014 Apr;21(2 Supp 1):98-105. Review. PubMed PMID: 24775731.

  Emerging therapies need time to be fully integrated into clinical practice in order to impact the survival for patients with metastatic prostate cancer.
• Kothari V, Goodwin JF, Zhao SG, Drake JM, Yin Y, Chang SL, Evans JR, Wilder-Romans K, Gabbara K, Dylgjeri E, Chou J, Sun G, Tomlins SA, Mehra R, Hege K, Filvaroff EH, Schaeffer EM, Karnes RJ, Quigley DA, Rathkopf DE, He HH, Speers C, Spratt DE, Gilbert LA, Ashworth A, Chinnaiyan AM, Raj GV, Knudsen KE, Feng FY. DNA-Dependent Protein Kinase Drives Prostate Cancer Progression through Transcriptional Regulation of the Wnt Signaling Pathway. Clin Cancer Res. 2019 Sep 15;25(18):5608-5622. doi: 10.1158/1078-0432.CCR-18-2387. Epub 2019 Jul 2. PMID: 31266829; PMCID: PMC6744969.DNAPK drives prostate cancer progression through transcriptional regulation of Wnt signaling and is an attractive therapeutic target in aggressive prostate cancer.

• Wang S, Kollipara RK, Humphries CG, Ma SH, Hutchinson R, Li R, Siddiqui J, Tomlins SA, Raj GV, Kittler R. The ubiquitin ligase TRIM25 targets ERG for degradation in prostate cancer. 2016 Oct 4;7(40):64921-64931. doi: 10.18632/oncotarget.11915. PubMed PMID: 27626314; PubMed Central PMCID: PMC5323126.

  ERG upregulates TRIM25 expression which is mitigated by the expression of the deubiquitinase USP9X

• 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. doi: 10.1073/pnas.1322198111. Epub 2014 Mar 3. PubMed PMID: 24591637; PubMed Central PMCID: PMC3964108.

  USP9X is a potential therapeutic target in prostate cancer cells and established WP1130 as a lead compound for the development of ERG-depleting drugs.

• Welti J, Sharp A, Yuan W, Dolling D, Nava Rodrigues D, Figueiredo I, Gil V, Neeb A, Clarke M, Seed G, Crespo M, Sumanasuriya S, Ning J, Knight E, Francis JC, Hughes A, Halsey WS, Paschalis A, Mani RS, Raj GV, Plymate SR, Carreira S, Boysen G, Chinnaiyan AM, Swain A, de Bono JS; International SU2C/PCF Prostate Cancer Dream Team.. Targeting Bromodomain and Extra-Terminal (BET) Family Proteins in Castration-Resistant Prostate Cancer (CRPC). Clin Cancer Res. 2018 Jul 1;24(13):3149-3162. doi: 10.1158/1078-0432.CCR-17-3571. Epub 2018 Mar 19. PubMed PMID: 29555663.

  Targeting bromodomain decreases persistent AR signaling and growth of a patient-derived xenograft model of CRPC with AR amplification and AR-V7 expression.

• Yang L, Ravindranathan P, Ramanan M, Kapur P, Hammes SR, Hsieh JT, Raj GV. Central role for PELP1 in nonandrogenic activation of the androgen receptor in prostate cancer. Mol Endocrinol. 2012 Apr;26(4):550-61. doi: 10.1210/me.2011-1101. Epub 2012 Mar 8. PubMed PMID: 22403175; PubMed Central PMCID: PMC5417135.

  PELP1 allows for crosstalk between E2 bound to ERβ and AR opening a therapeutic strategy in advanced PCa.

• Yin Y, Li R, Xu K, Ding S, Li J, Baek G, Ramanand SG, Ding S, Liu Z, Gao Y, Kanchwala MS, Li X, Hutchinson R, Liu X, Woldu SL, Xing C, Desai NB, Feng FY, Burma S, de Bono JS, Dehm SM, Mani RS, Chen BPC, Raj GV.Androgen receptor variants mediate DNA repair after prostate cancer irradiation. Cancer Res. 2017 Jul 28. pii: canres.0164.2017. doi: 10.1158/0008-5472.CAN-17-0164. [Epub ahead of print] PubMed PMID: 28754673.

  Pharmacologic inhibition of DNA-PKc elevated prostate cancer cell death after irradiation.

Breast Cancer

• Dang DN, Raj G, Sarode V, Molberg KH, Vadlamudi RK, Peng Y. Significantly increased PELP1 protein expression in primary and metastatic triple-negative breast carcinoma: comparison with GATA3 expression and PELP1's potential role in  triple-negative breast carcinoma. Hum Pathol. 2015 Dec;46(12):1829-35. doi: 10.1016/j.humpath.2015.07.023. Epub 2015 Aug 12. PubMed PMID: 26428280.

  PELP1 is a much more sensitive marker than GATA3 for TNBCs. PELP1 may have diagnostic utility for metastatic TNBC in some settings.

• Daniel AR, Gaviglio AL, Knutson TP, Ostrander JH, D'Assoro AB, Ravindranathan P, Peng Y, Raj GV, Yee D, Lange CA. Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes. 2015 Jan 22;34(4):506-15.  doi: 10.1038/onc.2013.579. Epub 2014 Jan 27. PubMed PMID: 24469035; PubMed Central PMCID: PMC4112172.

  Unliganded PR-B enhanced proliferative responses to estradiol and IGF1 via scaffolding of ER-α/PELP1/IGF1R-containing complexes.

• Ekoue DN, Unni N, Raj GV. A new class of agents for estrogen-receptor-positive breast cancer. Expert Rev Clin Pharmacol. 2018 Apr;11(4):325-328. doi: 10.1080/17512433.2018.1439736. PubMed PMID: 29439601.

  Agents like ERX-11 are leading into an exciting era of providing patients with more options and personalized tools in the management of breast cancer.

• Gonugunta VK, Miao L, Sareddy GR, Ravindranathan P, Vadlamudi R, Raj GV. The social network of PELP1 and its implications in breast and prostate cancers. Endocr Relat Cancer. 2014 Aug;21(4):T79-86. doi: 10.1530/ERC-13-0502. Epub 2014 May 23. Review. PubMed PMID: 24859989.

  The overexpression of PELP1 portends a poor prognosis for patients with hormone-related cancers.

• Hickey TE, Irvine CM, Dvinge H, Tarulli GA, Hanson AR, Ryan NK, Pickering MA, Birrell SN, Hu DG, Mackenzie PI, Russell R, Caldas C, Raj GV, Dehm SM, Plymate SR, Bradley RK, Tilley WD, Selth LA. Expression of androgen receptor splice variants in clinical breast cancers. 2015 Dec 29;6(42):44728-44. doi: 10.18632/oncotarget.6296. PubMed PMID: 26554309; PubMed Central PMCID: PMC4792588.

  AR-V7 is upregulated by the AR antagonist enzalutamide in primary breast tumors.

• Knutson TP, Truong TH, Ma S, Brady NJ, Sullivan ME, Raj G, Schwertfeger KL, Lange CA. Posttranslationally modified progesterone receptors direct ligand-specific expression of breast cancer stem cell-associated gene programs. J Hematol Oncol. 2017 Apr 17;10(1):89. doi: 10.1186/s13045-017-0462-7. PubMed PMID: 28412963; PubMed Central PMCID: PMC5392969.

  PR Ser294 phosphorylation is required to maintain breast cancer stem cell fate.

• Krishnan SR, Nair BC, Sareddy GR, Roy SS, Natarajan M, Suzuki T, Peng Y, Raj  G, Vadlamudi RK. Novel role of PELP1 in regulating chemotherapy response in mutant p53-expressing triple negative breast cancer cells. Breast Cancer Res Treat. 2015 Apr;150(3):487-99. doi: 10.1007/s10549-015-3339-x. Epub 2015 Mar 19.  PubMed PMID: 25788226; PubMed Central PMCID: PMC4385448.

  PELP1 is an important molecular target in TNBC, and that PELP1-targeted therapies may enhance response to chemotherapies.

• Mohammed H, Russell IA, Stark R, Rueda OM, Hickey TE, Tarulli GA, Serandour AA, Birrell SN, Bruna A, Saadi A, Menon S, Hadfield J, Pugh M, Raj GV, Brown GD,  D'Santos C, Robinson JL, Silva G, Launchbury R, Perou CM, Stingl J, Caldas C, Tilley WD, Carroll JS. Progesterone receptor modulates ERα action in breast cancer. 2015 Jul 16;523(7560):313-7. doi: 10.1038/nature14583. Epub 2015 Jul 8. Erratum in: Nature. 2015 Oct 1;526(7571):144.  Serandour, Aurelien A A[Corrected to Serandour, Aurelien A]. PubMed PMID: 26153859; PubMed Central PMCID: PMC4650274.

  PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.

• Raj GV, Sareddy GR, Ma S, Lee TK, Viswanadhapalli S, Li R, Liu X, Murakami S, Chen CC, Lee WR, Mann M, Krishnan SR, Manandhar B, Gonugunta VK, Strand D, Tekmal RR, Ahn JM, Vadlamudi RK. Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers. 2017 Aug 8;6. pii: e26857. doi: 10.7554/eLife.26857. PubMed PMID: 28786813; PubMed Central PMCID: PMC5548489.

  ERX11 is a first-in-class agent which may be clinically translatable for patients with therapy-sensitive and therapy-resistant breast cancers.

• Regan Anderson TM, Ma S, Perez Kerkvliet C, Peng Y, Helle TM, Krutilina RI, Raj GV, Cidlowski JA, Ostrander JH, Schwertfeger KL, Seagroves TN, Lange CA. Taxol Induces Brk-dependent Prosurvival Phenotypes in TNBC Cells through an AhR/GR/HIF-driven Signaling Axis. Mol Cancer Res. 2018 Nov;16(11):1761-1772. doi: 10.1158/1541-7786.MCR-18-0410. Epub 2018 Jul 10. PubMed PMID: 29991529; PubMed Central PMCID: PMC6214723.

  Brk was critical for TNBC cell proliferation and survival during Taxol treatment and in the context of ultra-low attachment.

• Regan Anderson TM, Ma SH, Raj GV, Cidlowski JA, Helle TM, Knutson TP, Krutilina RI, Seagroves TN, Lange CA. Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer. Cancer Res. 2016 Mar 15;76(6):1653-63. doi:10.1158/0008-5472.CAN-15-2510. Epub 2016 Jan 29. PubMed PMID: 26825173; PubMed Central PMCID: PMC4794366.

  Phospho-GR/HIF/PELP1 complex is a potential therapeutic target to limit Brk-driven progression and metastasis in TNBC patients.

• Roy S, Chakravarty D, Cortez V, De Mukhopadhyay K, Bandyopadhyay A, Ahn JM, Raj GV, Tekmal RR, Sun L, Vadlamudi RK. Significance of PELP1 in ER-negative breast cancer metastasis. Mol Cancer Res. 2012 Jan;10(1):25-33. doi: 10.1158/1541-7786.MCR-11-0456. Epub 2011 Nov 15. PubMed PMID: 22086908; PubMed Central PMCID: PMC3262052.

  PELP1 knockdown reduced the in vivo metastatic potential of ER-negative breast cancer cells and significantly reduced lung metastatic nodules in a xenograft assay.

• Singhal H, Greene ME, Tarulli G, Zarnke AL, Bourgo RJ, Laine M, Chang YF, Ma S, Dembo AG, Raj GV, Hickey TE, Tilley WD, Greene GL. Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer. Sci Adv. 2016 Jun 24;2(6):e1501924. doi: 10.1126/sciadv.1501924. eCollection 2016 Jun. PubMed PMID: 27386569; PubMed Central PMCID: PMC4928895.

  PR redirects ER chromatin binding to antagonize estrogen signaling suggesting that cotargeting of ER and PR in ER(+)/PR(+) breast cancers should be explored.
• Viswanadhapalli S, Ma S, Sareddy GR, Lee TK, Li M, Gilbreath C, Liu X, Luo Y, Pratap UP, Zhou M, Blatt EB, Kassees K, Arteaga C, Alluri P, Rao M, Weintraub ST, Tekmal RR, Ahn JM, Raj GV, Vadlamudi RK. Estrogen receptor coregulator binding modulator (ERX-11) enhances the activity of CDK4/6 inhibitors against estrogen receptor-positive breast cancers. Breast Cancer Res. 2019 Dec 26;21(1):150. doi: 10.1186/s13058-019-1227-8. PMID: 31878959; PMCID: PMC6933697.Combination therapy of ERX-11 and CDK4/6 inhibitors may be a promising therapeutic strategy for therapy-resistant BCa.

Clinically Relevant Models

• Centenera MM, Gillis JL, Hanson AR, Jindal S, Taylor RA, Risbridger GP, Sutherland PD, Scher HI, Raj GV, Knudsen KE, Yeadon T; Australian Prostate Cancer BioResource, Tilley WD, Butler LM. Evidence for efficacy of new Hsp90 inhibitors  revealed by ex vivo culture of human prostate tumors. Clin Cancer Res. 2012 Jul 1;18(13):3562-70. doi: 10.1158/1078-0432.CCR-12-0782. Epub 2012 May 9. PubMed PMID: 22573351.

  Ex vivo culture technique has provided information on Hsp90 inhibitor action not previously observed in cell lines or animal models.

• Centenera MM, Hickey TE, Jindal S, Ryan NK, Ravindranathan P, Mohammed H, Robinson JL, Schiewer MJ, Ma S, Kapur P, Sutherland PD, Hoffmann CE, Roehrborn CG, Gomella LG, Carroll JS, Birrell SN, Knudsen KE, Raj GV, Butler LM, Tilley WD. A patient-derived explant (PDE) model of hormone-dependent cancer. Mol Oncol. 2018 Sep;12(9):1608-1622. doi: 10.1002/1878-0261.12354. Epub 2018 Aug 16. PubMed PMID: 30117261; PubMed Central PMCID: PMC6120230.

  The PDE model provides the ability to rapidly evaluate drug efficacy in patient-derived material has high potential to facilitate implementation of personalized medicine approaches.

• Centenera MM, Raj GV, Knudsen KE, Tilley WD, Butler LM.Ex vivo culture of human prostate tissue and drug development. Nat Rev Urol. 2013 Aug;10(8):483-7. doi: 10.1038/nrurol.2013.126. Epub 2013 Jun 11. Review. PubMed PMID: 23752995.

  Ex vivo culture poised to accelerate translational "hit rate"  for prostate cancer research.

• Schiewer MJ, Goodwin JF, Han S, Brenner JC, Augello MA, Dean JL, Liu F, Planck JL, Ravindranathan P, Chinnaiyan AM, McCue P, Gomella LG, Raj GV, Dicker AP, Brody JR, Pascal JM, Centenera MM, Butler LM, Tilley WD, Feng FY, Knudsen KE. Dual roles of PARP-1 promote cancer growth and progression. Cancer Discov. 2012 Dec;2(12):1134-49. doi: 10.1158/2159-8290.CD-12-0120. Epub 2012 Sep 19. PubMed PMID: 22993403; PubMed Central PMCID: PMC3519969.

  DNA damage repair and transcription factor regulation offer a paradigm shift in PARP-1 function in human malignancy

• Shafi AA, Schiewer MJ, de Leeuw R, Dylgjeri E, McCue PA, Shah N, Gomella LG, Lallas CD, Trabulsi EJ, Centenera MM, Hickey TE, Butler LM, Raj G, Tilley WD, Cukierman E, Knudsen KE. Patient-derived Models Reveal Impact of the Tumor Microenvironment on Therapeutic Response. Eur Urol Oncol. 2018 Sep;1(4):325-337. doi: 10.1016/j.euo.2018.04.019. Epub 2018 Jun 6. PubMed PMID: 30467556; PubMed Central PMCID: PMC6241309.

  The PDE model allows for a comprehensive evaluation of individual tumors in their native TME to ultimately develop more effective therapeutic regimens

• 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. A validated tumorgraft model reveals activity of dovitinib against renal cell carcinoma. Sci Transl Med. 2012 Jun 6;4(137):137ra75. doi: 10.1126/scitranslmed.3003643. PubMed PMID: 22674553; PubMed Central PMCID: PMC3570965.

  Tumorgraft model recapitulates the molecular genetics and drug sensitivities of human tumors 

Therapy Resistance

• Chan SC, Selth LA, Li Y, Nyquist MD, Miao L, Bradner JE, Raj GV, Tilley WD, Dehm SM. Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res. 2015 Jul 13;43(12):5880-97. doi: 10.1093/nar/gkv262. Epub 2015 Apr 23. PubMed PMID: 25908785; PubMed Central PMCID: PMC4499120.

  JQ1 resulted in inhibition of AR-V chromatin binding and impaired AR-V driven PCa cell growth in vitro and in vivo.

• Henzler C, Li Y, Yang R, McBride T, Ho Y, Sprenger C, Liu G, Coleman I, Lakely B, Li R, Ma S, Landman SR, Kumar V, Hwang TH, Raj GV, Higano CS, Morrissey C, Nelson PS, Plymate SR, Dehm SM. Truncation and constitutive activation of the androgen receptor by diverse genomic rearrangements in prostate cancer. Nat Commun. 2016 Nov 29;7:13668. doi: 10.1038/ncomms13668. PubMed PMID: 27897170; PubMed Central PMCID: PMC5141345.

  AR genomic structural rearrangements are important drivers of persistent AR signalling in CRPC

• Krishnan SR, Nair BC, Sareddy GR, Roy SS, Natarajan M, Suzuki T, Peng Y, Raj  G, Vadlamudi RK. Novel role of PELP1 in regulating chemotherapy response in mutant p53-expressing triple negative breast cancer cells. Breast Cancer Res Treat. 2015 Apr;150(3):487-99. doi: 10.1007/s10549-015-3339-x. Epub 2015 Mar 19.  PubMed PMID: 25788226; PubMed Central PMCID: PMC4385448.

  PELP1 is an important molecular target in TNBC, and that PELP1-targeted therapies may enhance response to chemotherapies.

• Miao L, Yang L, Li R, Rodrigues DN, Crespo M, Hsieh JT, Tilley WD, de Bono J,  Selth LA, Raj GV. Disrupting Androgen Receptor Signaling Induces Snail-Mediated Epithelial-Mesenchymal Plasticity in Prostate Cancer. Cancer Res. 2017 Jun 1;77(11):3101-3112. doi: 10.1158/0008-5472.CAN-16-2169. Epub 2017 Mar 16. PubMed  PMID: 28302679.

  De-repression of Snail and induction of EMP is an adaptive response to enzalutamide with implications for therapy resistance.

• Paschalis A, Sharp A, Welti JC, Neeb A, Raj GV, Luo J, Plymate SR, de Bono JS. Alternative splicing in prostate cancer. Nat Rev Clin Oncol. 2018 Nov;15(11):663-675. doi: 10.1038/s41571-018-0085-0. Review. PubMed PMID: 30135575.

  Spliceosome modulation is a potential therapeutic avenue  against AR-Vs

• Singla N, Ghandour RA, Raj GV. Biomarkers for platinum sensitivity in bladder cancer: are we there yet? Transl Androl Urol. 2019 Jul;8(Suppl 3):S236-S239. doi:10.21037/tau.2019.01.10. PubMed PMID: 31392132Current prognostic biomarkers for the use of neoadjuvant chemotherapy in muscle-invasive bladder cancer are encouraging but need further investigation for wide use in the clininc.

• Thoreson GR, Gayed BA, Chung PH, Raj GV. Emerging therapies in castration resistant prostate cancer. Can J Urol. 2014 Apr;21(2 Supp 1):98-105. Review. PubMed PMID: 24775731.

  Emerging therapies need time to be fully integrated into clinical practice in order to impact the survival for patients with metastatic prostate cancer.

• Yin Y, Li R, Xu K, Ding S, Li J, Baek G, Ramanand SG, Ding S, Liu Z, Gao Y, Kanchwala MS, Li X, Hutchinson R, Liu X, Woldu SL, Xing C, Desai NB, Feng FY, Burma S, de Bono JS, Dehm SM, Mani RS, Chen BPC, Raj GV.Androgen receptor variants mediate DNA repair after prostate cancer irradiation. Cancer Res. 2017 Jul 28. pii: canres.0164.2017. doi: 10.1158/0008-5472.CAN-17-0164. [Epub ahead of print] PubMed PMID: 28754673.

  Pharmacologic inhibition of DNA-PKc elevated prostate cancer cell death after irradiation.

Novel Therapeutics

• Akram ON, DeGraff DJ, Sheehan JH, Tilley WD, Matusik RJ, Ahn JM, Raj GV. Tailoring peptidomimetics for targeting protein-protein interactions. Mol Cancer Res. 2014 Jul;12(7):967-78. doi: 10.1158/1541-7786.MCR-13-0611. Epub 2014 Mar 18. Review. PubMed PMID: 24642350.

  Agents that target PPIs is not only feasible but is of the utmost clinical importance.

• Ekoue DN, Unni N, Raj GV. A new class of agents for estrogen-receptor-positive breast cancer. Expert Rev Clin Pharmacol. 2018 Apr;11(4):325-328. doi: 10.1080/17512433.2018.1439736. PubMed PMID: 29439601.

  Agents like ERX-11 are leading into an exciting era of providing patients with more options and personalized tools in the management of breast cancer.

• Raj GV, Sareddy GR, Ma S, Lee TK, Viswanadhapalli S, Li R, Liu X, Murakami S,  Chen CC, Lee WR, Mann M, Krishnan SR, Manandhar B, Gonugunta VK, Strand D, Tekmal RR, Ahn JM, Vadlamudi RK. Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers. 2017 Aug 8;6. pii: e26857. doi: 10.7554/eLife.26857. PubMed PMID: 28786813; PubMed Central PMCID: PMC5548489.

  ERX11 is a first-in-class agent which may be clinically translatable for patients with therapy-sensitive and therapy-resistant breast cancers.

• Ravindranathan P, Lee TK, Yang L, Centenera MM, Butler L, Tilley WD, Hsieh JT, Ahn JM, Raj GV. Peptidomimetic targeting of critical androgen receptor-coregulator interactions in prostate cancer. Nat Commun. 2013;4:1923. doi: 10.1038/ncomms2912. PubMed PMID: 23715282.

  Using peptidomimetics targeting receptor-coregulator interactions may be a viable therapeutic approach for patients with advanced prostate cancer.

• Viswanadhapalli S, Ma S, Sareddy GR, Lee TK, Li M, Gilbreath C, Liu X, Luo Y, Pratap UP, Zhou M, Blatt EB, Kassees K, Arteaga C, Alluri P, Rao M, Weintraub ST, Tekmal RR, Ahn JM, Raj GV, Vadlamudi RK. Estrogen receptor coregulator binding modulator (ERX-11) enhances the activity of CDK4/6 inhibitors against estrogen receptor-positive breast cancers. Breast Cancer Res. 2019 Dec 26;21(1):150. doi: 10.1186/s13058-019-1227-8. PMID: 31878959; PMCID: PMC6933697.Combination therapy of ERX-11 and CDK4/6 inhibitors may be a promising therapeutic strategy for therapy-resistant BCa.

• Wang S, Ekoue DN, Raj GV, Kittler R. Targeting the turnover of oncoproteins as a new avenue for therapeutics development in castration-resistant prostate cancer. Cancer Lett. 2018 Dec 1;438:86-96. doi: 10.1016/j.canlet.2018.09.010. Epub 2018 Sep 11. PubMed PMID: 30217566; PubMed Central PMCID: PMC6186492.

  The development of specific agents for E3 ligases and deubiquitinases is still challenging. 

• 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. doi: 10.1073/pnas.1322198111. Epub 2014 Mar 3. PubMed PMID: 24591637; PubMed Central PMCID: PMC3964108.

   USP9X is a potential therapeutic target in prostate cancer cells and established WP1130 as a lead compound for the development of ERG-depleting drugs.

Nuclear Receptors

• Wang S, Gilbreath C, Kollipara RK, Sonavane R, Huo X, Yenerall P, Das A, Ma S, Raj GV, Kittler R. Mithramycin suppresses DNA damage repair via targeting androgen receptor in prostate cancer. Cancer Lett. 2020 Sep 28;488:40-49. doi:10.1016/j.canlet.2020.05.027. Epub 2020 May 30. PMID: 32485222.

  MTM treatment with RT or radiomimetic agents, may present a novel effective therapeutic strategy for patients with high-risk, clinically localized PCa.

• Ramanand SG, Chen Y, Yuan J, Daescu K, Lambros M, Houlahan KE, Carreira S,Yuan W, Baek G, Sharp A, Paschalis A, Kanchwala M, Gao Y, Aslam A, Safdar N, Zhan X, Raj GV, Xing C, Boutros PC, de Bono J, Zhang MQ, Mani RS. The landscape of RNA polymerase II associated chromatin interactions in prostate cancer. J Clin Invest. 2020 Apr 28. pii: 134260. doi:10.1172/JCI134260. [Epub ahead of print] PubMed PMID: 32343676.

  A novel germline-somatic interplay between the PCa risk allele rs684232 and the somatically acquired TMPRSS2-ERG gene fusion as a critical determinant of aberrant transcriptional regulation in PCa.

• Chan SC, Selth LA, Li Y, Nyquist MD, Miao L, Bradner JE, Raj GV, Tilley WD, Dehm SM. Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res. 2015 Jul 13;43(12):5880-97. doi: 10.1093/nar/gkv262. Epub 2015 Apr 23. PubMed PMID: 25908785; PubMed Central PMCID: PMC4499120.

  BET inhibition is a strategy for inhibiting expression and chromatin binding of AR-Vs in PCa.

• Duan L, Rai G, Roggero C, Zhang QJ, Wei Q, Ma SH, Zhou Y, Santoyo J, Martinez ED, Xiao G, Raj GV, Jadhav A, Simeonov A, Maloney DJ, Rizo J, Hsieh JT, Liu ZP. KDM4/JMJD2 Histone Demethylase Inhibitors Block Prostate Tumor Growth by Suppressing the Expression of AR and BMYB-Regulated Genes. Chem Biol. 2015 Sep 17;22(9):1185-96. doi: 10.1016/j.chembiol.2015.08.007. Epub 2015 Sep 10. PubMed PMID: 26364928; PubMed Central PMCID: PMC4578295.

  Our studies suggest a potential mechanism-based therapeutic strategy for PCa and tumors with elevated KDM4B/PLK1 expression.

• Henzler C, Li Y, Yang R, McBride T, Ho Y, Sprenger C, Liu G, Coleman I, Lakely B, Li R, Ma S, Landman SR, Kumar V, Hwang TH, Raj GV, Higano CS, Morrissey C, Nelson PS, Plymate SR, Dehm SM. Truncation and constitutive activation of the androgen receptor by diverse genomic rearrangements in prostate cancer. Nat Commun. 2016 Nov 29;7:13668. doi: 10.1038/ncomms13668. PubMed PMID: 27897170; PubMed Central PMCID: PMC5141345.

  AR genomic structural rearrangements are important drivers of persistent AR signalling in CRPC

• Hickey TE, Irvine CM, Dvinge H, Tarulli GA, Hanson AR, Ryan NK, Pickering MA, Birrell SN, Hu DG, Mackenzie PI, Russell R, Caldas C, Raj GV, Dehm SM, Plymate SR, Bradley RK, Tilley WD, Selth LA. Expression of androgen receptor splice variants in clinical breast cancers. 2015 Dec 29;6(42):44728-44. doi: 10.18632/oncotarget.6296. PubMed PMID: 26554309; PubMed Central PMCID: PMC4792588.

  AR-V7 is upregulated by the AR antagonist enzalutamide in primary breast tumors.

• Knutson TP, Truong TH, Ma S, Brady NJ, Sullivan ME, Raj G, Schwertfeger KL, Lange CA. Posttranslationally modified progesterone receptors direct ligand-specific expression of breast cancer stem cell-associated gene programs. J Hematol Oncol. 2017 Apr 17;10(1):89. doi: 10.1186/s13045-017-0462-7. PubMed PMID: 28412963; PubMed Central PMCID: PMC5392969.

  PR Ser294 phosphorylation is required to maintain breast cancer stem cell fate.

• Lee TK, Ravindranathan P, Sonavane R, Raj GV, Ahn JM. A Structure-Activity Relationship Study of Bis-Benzamides as Inhibitors of Androgen Receptor-Coactivator Interaction. Molecules. 2019 Jul 31;24(15):2783. doi: 10.3390/molecules24152783. PMID: 31370197; PMCID: PMC6696232.

          Inhibitor 14d exerts its anticancer activity by inhibiting the AR–PELP1 interaction and AR transactivation.

• Miao L, Yang L, Li R, Rodrigues DN, Crespo M, Hsieh JT, Tilley WD, de Bono J,  Selth LA, Raj GV. Disrupting Androgen Receptor Signaling Induces Snail-Mediated Epithelial-Mesenchymal Plasticity in Prostate Cancer. Cancer Res. 2017 Jun 1;77(11):3101-3112. doi: 10.1158/0008-5472.CAN-16-2169. Epub 2017 Mar 16. PubMed  PMID: 28302679.

  De-repression of Snail and induction of EMP is an adaptive response to enzalutamide with implications for therapy resistance.

• Mohammed H, Russell IA, Stark R, Rueda OM, Hickey TE, Tarulli GA, Serandour AA, Birrell SN, Bruna A, Saadi A, Menon S, Hadfield J, Pugh M, Raj GV, Brown GD,  D'Santos C, Robinson JL, Silva G, Launchbury R, Perou CM, Stingl J, Caldas C, Tilley WD, Carroll JS. Progesterone receptor modulates ERα action in breast cancer. 2015 Jul 16;523(7560):313-7. doi: 10.1038/nature14583. Epub 2015 Jul 8. Erratum in: Nature. 2015 Oct 1;526(7571):144.  Serandour, Aurelien A A[Corrected to Serandour, Aurelien A]. PubMed PMID: 26153859; PubMed Central PMCID: PMC4650274.

  PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.

• Regan Anderson TM, Ma SH, Raj GV, Cidlowski JA, Helle TM, Knutson TP, Krutilina RI, Seagroves TN, Lange CA. Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer. Cancer Res. 2016 Mar 15;76(6):1653-63. doi:10.1158/0008-5472.CAN-15-2510. Epub 2016 Jan 29. PubMed PMID: 26825173; PubMed Central PMCID: PMC4794366.

  Phospho-GR/HIF/PELP1 complex is a potential therapeutic target to limit Brk-driven progression and metastasis in TNBC patients.

• Schiewer MJ, Mandigo AC, Gordon N, Huang F, Gaur S, de Leeuw R, Zhao SG, Evans J, Han S, Parsons T, Birbe R, McCue P, McNair C, Chand SN, Cendon-Florez Y, Gallagher P, McCann JJ, Poudel Neupane N, Shafi AA, Dylgjeri E, Brand LJ, Visakorpi T, Raj GV, Lallas CD, Trabulsi EJ, Gomella LG, Dicker AP, Kelly WK, Leiby BE, Knudsen B, Feng FY, Knudsen KE. PARP-1 regulates DNA repair factor availability. EMBO Mol Med. 2018 Dec;10(12):e8816. doi: 10.15252/emmm.201708816. PMID: 30467127; PMCID: PMC6284389.PARP‐1 activity is increased as a function of disease progression and is associated with poor outcomes.

• Singhal H, Greene ME, Tarulli G, Zarnke AL, Bourgo RJ, Laine M, Chang YF, Ma S, Dembo AG, Raj GV, Hickey TE, Tilley WD, Greene GL. Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer. Sci Adv. 2016 Jun 24;2(6):e1501924. doi: 10.1126/sciadv.1501924. eCollection 2016 Jun. PubMed PMID: 27386569; PubMed Central PMCID: PMC4928895.

  PR redirects ER chromatin binding to antagonize estrogen signaling suggesting that cotargeting of ER and PR in ER(+)/PR(+) breast cancers should be explored.

• Toocheck C, Clister T, Shupe J, Crum C, Ravindranathan P, Lee TK, Ahn JM, Raj GV, Sukhwani M, Orwig KE, Walker WH.Mouse Spermatogenesis Requires Classical and Nonclassical Testosterone Signaling. Biol Reprod. 2016 Jan;94(1):11. doi: 10.1095/biolreprod.115.132068. Epub 2015 Nov 25. PubMed PMID: 26607719; PubMedCentral PMCID: PMC4809556.

  Classical and nonclassical testosterone signaling regulate overlapping and distinct functions that are required for the maintenance of spermatogenesis and male fertility.

• Yang L, Ravindranathan P, Ramanan M, Kapur P, Hammes SR, Hsieh JT, Raj GV. Central role for PELP1 in nonandrogenic activation of the androgen receptor in prostate cancer. Mol Endocrinol. 2012 Apr;26(4):550-61. doi: 10.1210/me.2011-1101. Epub 2012 Mar 8. PubMed PMID: 22403175; PubMed Central PMCID: PMC5417135.

  PELP1 allows for crosstalk between E2 bound to ERβ and AR opening a therapeutic strategy in advanced PCa.

• Zhang B, Kwon OJ, Henry G, Malewska A, Wei X, Zhang L, Brinkley W, Zhang Y, Castro PD, Titus M, Chen R, Sayeeduddin M, Raj GV, Mauck R, Roehrborn C, Creighton CJ, Strand DW, Ittmann MM, Xin L. Non-Cell-Autonomous Regulation of Prostate Epithelial Homeostasis by Androgen Receptor. Mol Cell. 2016 Sep 15;63(6):976-89. doi: 10.1016/j.molcel.2016.07.025. Epub 2016 Sep 1. PubMed PMID: 27594448; PubMed Central PMCID: PMC5026614.

  Disrupting luminal AR signaling promotes prostate inflammation, which may serve as a mechanism for resistance to androgen-targeted therapy for prostate-related diseases.