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.

Research Funding

  • September 6, 2022 - September 5, 2024 - Advancing the Drug Development Process in Metastatic Prostate Cancer through Machine Learning , co-PI . Sponsor: Prostate Cancer Foundation, Sponsor Award ID: 22CHAS02

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. Chappidi MR, Sjöström M, Greenland NY, Cowan JE, Baskin AS, Shee K, Simko JP, Chan E, Stohr BA, Washington SL, Nguyen HG, Quigley DA, Davicioni E, Feng FY, Carroll PR, Cooperberg MR. Transcriptomic Heterogeneity of Expansile Cribriform and Other Gleason Pattern 4 Prostate Cancer Subtypes. Eur Urol Oncol. 2023 Jul 18.  View on PubMed
  2. Helzer KT, Sharifi MN, Sperger JM, Shi Y, Annala M, Bootsma ML, Reese SR, Taylor A, Kaufmann KR, Krause HK, Schehr JL, Sethakorn N, Kosoff D, Kyriakopoulos C, Burkard ME, Rydzewski NR, Yu M, Harari PM, Bassetti M, Blitzer G, Floberg J, Sjöström M, Quigley DA, Dehm SM, Armstrong AJ, Beltran H, McKay RR, Feng FY, O'Regan R, Wisinski KB, Emamekhoo H, Wyatt AW, Lang JM, Zhao SG. Fragmentomic analysis of circulating tumor DNA-targeted cancer panels. Ann Oncol. 2023 09; 34(9):813-825.  View on PubMed
  3. Lundberg A, Zhang M, Aggarwal R, Li H, Zhang L, Foye A, Sjöström M, Chou J, Chang K, Moreno-Rodriguez T, Shrestha R, Baskin A, Zhu X, Weinstein AS, Younger N, Alumkal JJ, Beer TM, Chi KN, Evans CP, Gleave M, Lara PN, Reiter RE, Rettig MB, Witte ON, Wyatt AW, Feng FY, Small EJ, Quigley DA. The genomic and epigenomic landscape of double-negative metastatic prostate cancer. Cancer Res. 2023 Jun 08.  View on PubMed
  4. Xiaolin Zhu, Daniël Vis, Martin Sjöström, Raunak Shrestha, Jeroen Kneppers, Tesa Severson, Yanyun Zhu, Meng Zhang, Arian Lundberg, Thaidy Moreno Rodriguez, Alana Weinstein, Haolong Li, Adam Foye, Rahul Aggarwal, Andries M Bergman, Eric Small, Wilbert Zwart, David Quigley, Michiel van der Heijden, Felix Feng. Abstract A029: Whole genome and transcriptome analysis of paired metastatic biopsies identified resistance mechanisms in castration-resistant prostate cancer. Cancer Research. 2023 Jun 2; 83(11_Supplement):a029-a029.  View on PubMed
  5. Meng Zhang, Martin Sjöström, Raunak Shrestha, Arian Lundberg, Thaidy Moreno-Rodriguez, Adam Foye, Ha X. Dang, Joshi J. Alumkal, Rahul Aggarwal, Eric J. Small, Christopher A. Maher, Felix Y. Feng, David Quigley. Abstract A062: Alternative promoter usage is linked to transcriptional and epigenetic alterations during prostate cancer progression. Cancer Research. 2023 Jun 2; 83(11_Supplement):a062-a062.  View on PubMed
  6. Thaidy Moreno, Meng Zhang, Arian Lundberg, Raunak Shrestha, Martin Sjöström, Anu Pasam, Adam Foye, Anna Trigos, Felix Feng, Shahneen Sandhu, David A. Quigley. Abstract PR003: Convergent evolution in DNA repair-deficient mCRPC in response to targeted therapy. Cancer Research. 2023 Jun 2; 83(11_Supplement):pr003-pr003.  View on PubMed
  7. Taylor MA, Kandyba E, Halliwill K, Delrosario R, Koroshkin M, Goodarzi H, Quigley D, Li YR, Wu D, Bollam S, Mirzoeva O, Akhurst RJ, Balmain A. Gene networks reveal stem-cell state convergence during preneoplasia and progression to malignancy in multistage skin carcinogenesis. bioRxiv. 2023 May 10.  View on PubMed
  8. 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 04 10; 8(7).  View on PubMed
  9. Feng E, Rydzewski NR, Zhang M, Lundberg A, Bootsma M, Helzer KT, Lang JM, Aggarwal R, Small EJ, Quigley DA, Sjöström 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
  10. 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
  11. Sjöström 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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

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