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. Herberts C, Annala M, Sipola J, Ng SWS, Chen XE, Nurminen A, Korhonen OV, Munzur AD, Beja K, Schönlau 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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, Sjöström 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
  7. Rydzewski NR, Peterson E, Lang JM, Yu M, Laura Chang S, Sjöström 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
  8. Das R, Sjöström 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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, Sjöström 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
  15. Guan X, Sun D, Lu E, Urrutia JA, Reiter RE, Rettig M, Evans CP, Lara P, Gleave M, Beer TM, Thomas GV, Huang J, Aggarwal RR, Quigley DA, Foye A, Chen WS, Youngren J, Weinstein AS, Stuart JM, Feng FY, Small EJ, Xia Z, Alumkal JJ. Copy Number Loss of 17q22 Is Associated with Enzalutamide Resistance and Poor Prognosis in Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2020 09 01; 26(17):4616-4624.  View on PubMed
  16. Zhao SG, Chen WS, Li H, Foye A, Zhang M, Sjöström M, Aggarwal R, Playdle D, Liao A, Alumkal JJ, Das R, Chou J, Hua JT, Barnard TJ, Bailey AM, Chow ED, Perry MD, Dang HX, Yang R, Moussavi-Baygi R, Zhang L, Alshalalfa M, Laura Chang S, Houlahan KE, Shiah YJ, Beer TM, Thomas G, Chi KN, Gleave M, Zoubeidi A, Reiter RE, Rettig MB, Witte O, Yvonne Kim M, Fong L, Spratt DE, Morgan TM, Bose R, Huang FW, Li H, Chesner L, Shenoy T, Goodarzi H, Asangani IA, Sandhu S, Lang JM, Mahajan NP, Lara PN, Evans CP, Febbo P, Batzoglou S, Knudsen KE, He HH, Huang J, Zwart W, Costello JF, Luo J, Tomlins SA, Wyatt AW, Dehm SM, Ashworth A, Gilbert LA, Boutros PC, Farh K, Chinnaiyan AM, Maher CA, Small EJ, Quigley DA, Feng FY. The DNA methylation landscape of advanced prostate cancer. Nat Genet. 2020 08; 52(8):778-789.  View on PubMed
  17. Kwon DH, Zhang L, Quigley DA, Foye A, Chen WS, Wong CK, Feng FY, Bailey A, Huang J, Stuart JM, Friedl V, Weinstein AS, Beer TM, Alumkal JJ, Rettig M, Gleave M, Lara PN, Thomas GV, Li P, Lui A, Small EJ, Aggarwal RR. Down-regulation of ADRB2 expression is associated with small cell neuroendocrine prostate cancer and adverse clinical outcomes in castration-resistant prostate cancer. Urol Oncol. 2020 12; 38(12):931.e9-931.e16.  View on PubMed
  18. Eric Jay Small, Shuang Zhao, William S. Chen, Haolong Li, Adam Foye, Martin Sjöström, Jun Jie Hua, Rahul Raj Aggarwal, Joshi J. Alumkal, Tomasz M. Beer, Martin Gleave, Matthew Rettig, Owen Witte, Primo Lara, Arul Chinnaiyan, Chris Maher, David A. Quigley, Felix Y Feng. The comprehensive methylation landscape of metastatic castration-resistant prostate cancer (mCRPC) identifies new phenotypic subtypes: Results from the West Coast Prostate Cancer Dream Team (WCDT). Journal of Clinical Oncology. 2020 May 20; 38(15_suppl):5507-5507.  View on PubMed
  19. Alumkal JJ, Sun D, Lu E, Beer TM, Thomas GV, Latour E, Aggarwal R, Cetnar J, Ryan CJ, Tabatabaei S, Bailey S, Turina CB, Quigley DA, Guan X, Foye A, Youngren JF, Urrutia J, Huang J, Weinstein AS, Friedl V, Rettig M, Reiter RE, Spratt DE, Gleave M, Evans CP, Stuart JM, Chen Y, Feng FY, Small EJ, Witte ON, Xia Z. Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance. Proc Natl Acad Sci U S A. 2020 06 02; 117(22):12315-12323.  View on PubMed
  20. Pierson WE, Peters PN, Chang MT, Chen LM, Quigley DA, Ashworth A, Chapman JS. An integrated molecular profile of endometrioid ovarian cancer. Gynecol Oncol. 2020 04; 157(1):55-61.  View on PubMed

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