Research Summary

I study how genomic and epigenomic alterations affect tumor biology and patient outcomes. I have a particular interest in understanding how urological tumors develop resistance to targeted therapy. Recent projects have used large-scale genome sequencing to identify non-coding DNA structural variants associated with therapy resistance in advanced prostate cancer (Quigley Cell 2018) and a novel prostate cancer epigenomic disease subtype (Zhao Nature Genetics 2020). To achieve our goals, the laboratory works in close collaboration with physicians and laboratory investigators, and uses a wide variety of genome sequencing methods to study patient biopsy samples and preclinical models. This includes analysis of therapy resistance mechanisms in patients using liquid biopsy techniques and whole genome analysis of tumors. The lab has a long-term interest in understanding how inherited or somatic defects in homologous recombination repair (HRR) affect tumor genomes, and how to detect and overcome resistance to targeted PARP inhibitor therapy in patients with HRR-deficient tumors.

Education

Carleton College, BA, 1998, Computer Science
Columbia University, MA, 2006, Biomedical Informatics
University of Oslo, PhD, 2014, Genetics

Honors & Awards

  • 1998
    National Merit Scholar. B.A. degree awarded Magna Cum Laude
  • 2006
    M.A. degree awarded with honors
  • 2014
    AACR Scholar in Training award
  • 2017
    Prostate Cancer Foundation Young Investigator Award
  • 2018
    BRCA Foundation Young Investigator Award

Selected Publications

  1. Sayar E, Patel RA, Coleman IM, Roudier MP, Zhang A, Mustafi P, Low JY, Hanratty B, Ang LS, Bhatia V, Adil M, Bakbak H, Quigley DA, Schweizer MT, Hawley JE, Kollath L, True LD, Feng FY, Bander NH, Corey E, Lee JK, Morrissey C, Gulati R, Nelson PS, Haffner MC. Reversible epigenetic alterations mediate PSMA expression heterogeneity in advanced metastatic prostate cancer. JCI Insight. 2023 Feb 23.  View on PubMed
  2. Feng E, Rydzewski NR, Zhang M, Lundberg A, Bootsma M, Helzer KT, Lang JM, Aggarwal R, Small EJ, Quigley DA, Sj?str?m M, Zhao SG. Intrinsic Molecular Subtypes of Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2022 12 15; 28(24):5396-5404.  View on PubMed
  3. O'Leary PC, Chen H, Doruk YU, Williamson T, Polacco B, McNeal AS, Shenoy T, Kale N, Carnevale J, Stevenson E, Quigley DA, Chou J, Feng FY, Swaney DL, Krogan NJ, Kim M, Diolaiti ME, Ashworth A. Resistance to ATR Inhibitors Is Mediated by Loss of the Nonsense-Mediated Decay Factor UPF2. Cancer Res. 2022 11 02; 82(21):3950-3961.  View on PubMed
  4. Sj?str?m M, Zhao SG, Levy S, Zhang M, Ning Y, Shrestha R, Lundberg A, Herberts C, Foye A, Aggarwal R, Hua JT, Li H, Bergamaschi A, Maurice-Dror C, Maheshwari A, Chen S, Ng SWS, Ye W, Petricca J, Fraser M, Chesner L, Perry MD, Moreno-Rodriguez T, Chen WS, Alumkal JJ, Chou J, Morgans AK, Beer TM, Thomas GV, Gleave M, Lloyd P, Phillips T, McCarthy E, Haffner MC, Zoubeidi A, Annala M, Reiter RE, Rettig MB, Witte ON, Fong L, Bose R, Huang FW, Luo J, Bjartell A, Lang JM, Mahajan NP, Lara PN, Evans CP, Tran PT, Posadas EM, He C, Cui XL, Huang J, Zwart W, Gilbert LA, Maher CA, Boutros PC, Chi KN, Ashworth A, Small EJ, He HH, Wyatt AW, Quigley DA, Feng FY. The 5-Hydroxymethylcytosine Landscape of Prostate Cancer. Cancer Res. 2022 11 02; 82(21):3888-3902.  View on PubMed
  5. Westbrook TC, Guan X, Rodansky E, Flores D, Liu CJ, Udager AM, Patel RA, Haffner MC, Hu YM, Sun D, Beer TM, Foye A, Aggarwal R, Quigley DA, Youngren JF, Ryan CJ, Gleave M, Wang Y, Huang J, Coleman I, Morrissey C, Nelson PS, Evans CP, Lara P, Reiter RE, Witte O, Rettig M, Wong CK, Weinstein AS, Uzunangelov V, Stuart JM, Thomas GV, Feng FY, Small EJ, Yates JA, Xia Z, Alumkal JJ. Transcriptional profiling of matched patient biopsies clarifies molecular determinants of enzalutamide-induced lineage plasticity. Nat Commun. 2022 09 15; 13(1):5345.  View on PubMed
  6. Zhang M, Moreno-Rodriguez T, Quigley DA. Why ARNT Prostate Tumors Responding to Enzalutamide? Cancer Discov. 2022 09 02; 12(9):2017-2019.  View on PubMed
  7. Herberts C, Annala M, Sipola J, Ng SWS, Chen XE, Nurminen A, Korhonen OV, Munzur AD, Beja K, Sch?nlau E, Bernales CQ, Ritch E, Bacon JVW, Lack NA, Nykter M, Aggarwal R, Small EJ, Gleave ME, SU2C/PCF West Coast Prostate Cancer Dream Team, Quigley DA, Feng FY, Chi KN, Wyatt AW. Deep whole-genome ctDNA chronology of treatment-resistant prostate cancer. Nature. 2022 08; 608(7921):199-208.  View on PubMed
  8. Cameron Herberts, Matti Annala, Joonatan Sipola, Sarah W. Ng, Xinyi E. Chen, Anssi Nurminen, Olga Korhonen, Asli D. Munzur, Kevin Beja, Elena Schönlau, Cecily Q. Bernales, Elie Ritch, Jack V. Bacon, Nathan A. Lack, Matti Nykter, Rahul Aggarwal, Eric J. Small, Martin E. Gleave, David A. Quigley, Felix Y. Feng, Kim N. Chi, Alexander W. Wyatt. Abstract 3625: Clonal architecture and evolution of treatment-resistant prostate cancer via deep whole-genome ctDNA sequencing. Cancer Research. 2022 Jun 15; 82(12_Supplement):3625-3625.  View on PubMed
  9. Severson T, Qiu X, Alshalalfa M, Sjöström M, Quigley D, Bergman A, Long H, Feng F, Freedman ML, Zwart W, Pomerantz MM. Androgen receptor reprogramming demarcates prognostic, context-dependent gene sets in primary and metastatic prostate cancer. Clin Epigenetics. 2022 05 04; 14(1):60.  View on PubMed
  10. Ivan de Kouchkovsky, Li Zhang, Jiaoti Huang, Kai Trepka, Jonathan Chou, Adam Foye, David Shui, Chris Wong, Verena Friedl, Alana Weinstein, Thomas A Hope, David A. Quigley, Josh Stuart, Tomasz M. Beer, Robert Evan Reiter, Martin E. Gleave, Christopher P Evans, Felix Y Feng, Eric Jay Small, Rahul Raj Aggarwal. Clinical and molecular features of low prostate-specific membrane antigen (PSMA) expression in patients (pts) with metastatic castration resistant prostate cancer (mCRPC). Journal of Clinical Oncology. 2022 Feb 20; 40(6_suppl):167-167.  View on PubMed
  11. Seock-Ah Im, Kyung-Hun Lee, Ahrum Min, Daewon Lee, Tae Yong Kim, Han Suk Ryu, Jiwon Koh, Gi-Jeong Cheon, Yoon-Jung Shin, Yujin Kim, Hyeong-Gon Moon, Wonshik Han, Han-Byoel Lee, Morgan Diolaiti, David Quigley, Alan Ashworth, Nariya Cho. Abstract PD15-08: Window of opportunity trial of neoadjuvant olaparib and durvalumab for triple negative or low ER-positive breast cancer. Cancer Research. 2022 Feb 15; 82(4_Supplement):pd15-08-pd15-08.  View on PubMed
  12. Aggarwal R, Rydzewski NR, Zhang L, Foye A, Kim W, Helzer KT, Bakhtiar H, Chang SL, Perry MD, Gleave M, Reiter RE, Huang J, Evans CP, Alumkal JJ, Lang JM, Yu M, Quigley DA, Sj?str?m M, Small EJ, Feng FY, Zhao SG. Prognosis Associated With Luminal and Basal Subtypes of Metastatic Prostate Cancer. JAMA Oncol. 2021 Nov 01; 7(11):1644-1652.  View on PubMed
  13. Rydzewski NR, Peterson E, Lang JM, Yu M, Laura Chang S, Sj?str?m M, Bakhtiar H, Song G, Helzer KT, Bootsma ML, Chen WS, Shrestha RM, Zhang M, Quigley DA, Aggarwal R, Small EJ, Wahl DR, Feng FY, Zhao SG. Predicting cancer drug TARGETS - TreAtment Response Generalized Elastic-neT Signatures. NPJ Genom Med. 2021 Sep 21; 6(1):76.  View on PubMed
  14. Das R, Sj?str?m M, Shrestha R, Yogodzinski C, Egusa EA, Chesner LN, Chen WS, Chou J, Dang DK, Swinderman JT, Ge A, Hua JT, Kabir S, Quigley DA, Small EJ, Ashworth A, Feng FY, Gilbert LA. An integrated functional and clinical genomics approach reveals genes driving aggressive metastatic prostate cancer. Nat Commun. 2021 07 29; 12(1):4601.  View on PubMed
  15. Ahmed M, Soares F, Xia JH, Yang Y, Li J, Guo H, Su P, Tian Y, Lee HJ, Wang M, Akhtar N, Houlahan KE, Bosch A, Zhou S, Mazrooei P, Hua JT, Chen S, Petricca J, Zeng Y, Davies A, Fraser M, Quigley DA, Feng FY, Boutros PC, Lupien M, Zoubeidi A, Wang L, Walsh MJ, Wang T, Ren S, Wei GH, He HH. CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism in prostate cancer. Nat Commun. 2021 03 19; 12(1):1781.  View on PubMed
  16. Martin Sjöström, Shuang Zhao, Eric Jay Small, Yuhong Ning, Corinne Maurice-Dror, Adam Foye, Jun Jie T. Hua, Haolong Li, Tomasz M. Beer, Christopher P. Evans, Matthew Rettig, Kim N. Chi, Joshi J. Alumkal, Rahul Raj Aggarwal, Alan Ashworth, Samuel Levy, Housheng H. He, Alexander W. Wyatt, David A. Quigley, Felix Y Feng. 5-hydroxymethylcytosine as a liquid biopsy biomarker in mCRPC. Journal of Clinical Oncology. 2021 Feb 20; 39(6_suppl):148-148.  View on PubMed
  17. Ivan de Kouchkovsky, David A. Quigley, Eric J. Small, Rahul Aggarwal. Genomic characterization of treatment-associated small cell neuroendocrine carcinoma of the prostate. Journal of Translational Genetics and Genomics. 2021 Jan 1; 5(3):265-277.  View on PubMed
  18. Quigley DA. One of These Things is Not Like the Others: Targeting ATM-mutant Prostate Cancer. Eur Urol. 2021 02; 79(2):212-213.  View on PubMed
  19. Eteleeb AM, Quigley DA, Zhao SG, Pham D, Yang R, Dehm SM, Luo J, Feng FY, Dang HX, Maher CA. SV-HotSpot: detection and visualization of hotspots targeted by structural variants associated with gene expression. Sci Rep. 2020 09 28; 10(1):15890.  View on PubMed
  20. Chen WS, Haynes WA, Waitz R, Kamath K, Vega-Crespo A, Shrestha R, Zhang M, Foye A, Baselga Carretero I, Perez Garcilazo I, Zhang M, Zhao SG, Sj?str?m M, Quigley DA, Chou J, Beer TM, Rettig M, Gleave M, Evans CP, Lara P, Chi KN, Reiter RE, Alumkal JJ, Ashworth A, Aggarwal R, Small EJ, Daugherty PS, Ribas A, Oh DY, Shon JC, Feng FY. Autoantibody Landscape in Patients with Advanced Prostate Cancer. Clin Cancer Res. 2020 12 01; 26(23):6204-6214.  View on PubMed

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