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

  • July 1, 2024 – June 30, 2029 - UCSF Specialized Programs of Research Excellence (SPORE) in Prostate Cancer. Role: core co-director Sponsor: NCI. Sponsor award ID: 1P50CA275741
  • May 1, 2024 - April 30, 2027 - Discovering transcriptional drivers of therapy-resistant metastatic prostate cancer , PI . Sponsor: DOD, Sponsor Award ID: PC230564

  • December 4, 2023 - December 3, 2026 - PCF SYNERGY Tactical award Role: co-PI. Sponsor: Prostate Cancer Foundation. Sponsor award ID: 23TACT01

  • 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
  • 2024
    Robert Sutherland Award, PacRim Breast and Prostate Cancer Meeting
  • 2024
    Outstanding Faculty Mentorship Award, UCSF Students of the Graduate Division

Selected Publications

  1. E. Feng, J.M.A. Vo-Phamhi, A. Foye, J. Vinson, J.C. Hong, S.J. Freedland, J. Alumkal, H. Beltran, C. Morrissey, P. Nelson, A. Chinnaiyan, C. Sawyers, R. Aggarwal, E. Small, D. Quigley, M. Sjostrom, S.G. Zhao, W.S. Chen. Racial Variation in the Advanced Prostate Cancer Genome. International Journal of Radiation Oncology • Biology • Physics. 2024 Oct 1; 120(2):e519.  View on PubMed
  2. Chou J, Robinson TM, Egusa EA, Lodha R, Zhang M, Badura M, Mikayelyan M, Delavan H, Swinderman J, Wilson C, Zhu J, Das R, Nguyen M, Loehr A, Golsorkhi T, Simmons A, Abida W, Chinnaiyan AM, Arkin MR, Small EJ, Quigley DA, Yang L, Kim M, Ashworth A, Feng FY. Synthetic Lethal Targeting of Cyclin Dependent Kinase-12-Deficient Prostate Cancer with PARP Inhibitors. Clin Cancer Res. 2024 Sep 25.  View on PubMed
  3. Shrestha R, Chesner LN, Zhang M, Zhou S, Foye A, Lundberg A, Weinstein AS, Sjöström M, Zhu X, Moreno-Rodriguez T, Li H, SU2C/PCF West Coast Prostate Cancer Dream Team, Alumkal JJ, Aggarwal R, Small EJ, Lupien M, Quigley DA, Feng FY. An Atlas of Accessible Chromatin in Advanced Prostate Cancer Reveals the Epigenetic Evolution during Tumor Progression. Cancer Res. 2024 Sep 16; 84(18):3086-3100.  View on PubMed
  4. Zhu X, Farsh T, Vis D, Yu I, Li H, Liu T, Sjöström M, Shrestha R, Kneppers J, Severson T, Zhang M, Lundberg A, Moreno Rodriguez T, Weinstein AS, Foye A, Mehra N, Aggarwal RR, Bergman AM, Small EJ, Lack NA, Zwart W, Quigley DA, van der Heijden MS, Feng FY. Genomic and transcriptomic features of androgen receptor signaling inhibitor resistance in metastatic castration-resistant prostate cancer. J Clin Invest. 2024 Aug 13; 134(19).  View on PubMed
  5. Zhu X, Chan E, Turski ML, Mendez CE, Hsu SC, Kumar V, Shipp C, Jindal T, Chang K, Onodera C, Devine WP, Grenert JP, Stohr BA, Ding CC, Stachler MD, Quigley DA, Feng FY, Chu CE, Porten SP, Chou J, Friedlander TW, Koshkin VS. HER2 overexpression in urothelial carcinoma with GATA3 and PPARG copy number gains. Oncologist. 2024 Aug 05; 29(8):e1094-e1097.  View on PubMed
  6. Zhao SG, Bootsma M, Zhou S, Shrestha R, Moreno-Rodriguez T, Lundberg A, Pan C, Arlidge C, Hawley JR, Foye A, Weinstein AS, Sjöström M, Zhang M, Li H, Chesner LN, Rydzewski NR, Helzer KT, Shi Y, West Coast Dream Team Consortium, Lynch M, Dehm SM, Lang JM, Alumkal JJ, He HH, Wyatt AW, Aggarwal R, Zwart W, Small EJ, Quigley DA, Lupien M, Feng FY. Integrated analyses highlight interactions between the three-dimensional genome and DNA, RNA and epigenomic alterations in metastatic prostate cancer. Nat Genet. 2024 Aug; 56(8):1689-1700.  View on PubMed
  7. Zhang M, Sjöström M, Cui X, Foye A, Farh K, Shrestha R, Lundberg A, Dang HX, Li H, Febbo PG, Aggarwal R, Alumkal JJ, Small EJ, SU2C/PCF West Coast Prostate Cancer Dream Team, Maher CA, Feng FY, Quigley DA. Integrative analysis of ultra-deep RNA-seq reveals alternative promoter usage as a mechanism of activating oncogenic programmes during prostate cancer progression. Nat Cell Biol. 2024 Jul; 26(7):1176-1186.  View on PubMed
  8. Subramanian A, Zhang M, Sharifi M, Moreno-Rodriguez T, Feng E, Rydzewski NR, Shrestha R, Zhu X, Zhao SG, Aggarwal R, Small EJ, Ding CC, Quigley DA, Sjöström M. A prostate cancer gastrointestinal transcriptional phenotype may be associated with diminished response to AR-targeted therapy. bioRxiv. 2024 Jun 03.  View on PubMed
  9. Ali Sabbagh, David Alan Quigley, Nicholas Lillis, Li Zhang, Isabel D Friesner, Adina Bailey, Rahul Raj Aggarwal, Meera Reddy Chappidi, Hari Singhal, Ke Zhang, Joel Greshock, Jinhui Li, Margaret K. Yu, Eric J. Small, Julian C. Hong. Development of a machine learning model to predict overall survival results from randomized clinical trials of patients with metastatic prostate cancer. Journal of Clinical Oncology. 2024 Jun 1; 42(16_suppl):5065-5065.  View on PubMed
  10. Taylor MA, Kandyba E, Halliwill K, Delrosario R, Khoroshkin M, Goodarzi H, Quigley D, Li YR, Wu D, Bollam SR, Mirzoeva OK, Akhurst RJ, Balmain A. Stem-cell states converge in multistage cutaneous squamous cell carcinoma development. Science. 2024 May 31; 384(6699):eadi7453.  View on PubMed
  11. Raunak Shrestha, Lisa N. Chesner, Meng Zhang, Stanley Zhou, Adam Foye, Arian Lundberg, Alana S. Weinstein, Martin Sjöström, Xiaolin Zhu, Thaidy Moreno-Rodriguez, Haolong Li, Joshi J. Alumkal, Rahul Aggarwal, Eric J. Small, Mathieu Lupien, David A. Quigley, Felix Y. Feng. Abstract LB196: An atlas of accessible chromatin in advanced prostate cancer. Cancer Research. 2024 Apr 5; 84(7_Supplement):lb196-lb196.  View on PubMed
  12. Saha D, Dang HX, Zhang M, Quigley DA, Feng FY, Maher CA. Single cell-transcriptomic analysis informs the lncRNA landscape in metastatic castration resistant prostate cancer. NPJ Genom Med. 2024 Feb 23; 9(1):14.  View on PubMed
  13. David Alan Quigley, Julian C. Hong, Nicholas Lillis, Ali Sabbagh, Isabel D Friesner, Adina Bailey, Rahul Raj Aggarwal, Li Zhang, Meera Reddy Chappidi, Hari Singhal, Joel Greshock, Ke Zhang, Margaret K. Yu, Eric J. Small. Advancing the drug development process in metastatic prostate cancer through machine learning. Journal of Clinical Oncology. 2024 Feb 1; 42(4_suppl):192-192.  View on PubMed
  14. Aishwarya Subramanian, Meng Zhang, Marina Nasrin Sharifi, Thaidy Moreno Rodriguez, Eric Feng, Nicholas Robert Rydzewski, Raunak Shrestha, Xiaolin Zhu, Shuang Zhao, Rahul Raj Aggarwal, Eric J. Small, Chien-Kuang Cornelia Ding, David Alan Quigley, Martin Sjöström. Association of a prostate cancer gastrointestinal transcriptional phenotype as found in clinical mCRPC samples with response to AR-targeted therapy. Journal of Clinical Oncology. 2024 Feb 1; 42(4_suppl):203-203.  View on PubMed
  15. Xiaolin Zhu, Daniel J Vis, Martin Sjöström, Raunak Shrestha, Jeroen Kneppers, Tessa Severson, Yanyun Zhu, Haolong Li, Tatyanah Farsh, Meng Zhang, Arian Lundberg, Thaidy Moreno Rodriguez, Adam Foye, Andre M. Bergman, Wilbert Zwart, David Alan Quigley, Rahul Raj Aggarwal, Eric J. Small, Michiel Simon Van Der Heijden, Felix Y Feng. Somatostatin receptor 1 ( SSTR1 ) expression as a potential predictive biomarker for response to androgen receptor signaling inhibitor (ARSI) therapy in metastatic castration-resistant prostate cancer (mCRPC). Journal of Clinical Oncology. 2024 Feb 1; 42(4_suppl):180-180.  View on PubMed
  16. 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 08 15; 83(16):2763-2774.  View on PubMed
  17. Moreno T, Magana J, Quigley DA. AARDVARK: an automated reversion detector for variants affecting resistance kinetics. Bioinformatics. 2023 08 01; 39(8).  View on PubMed
  18. 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. 2024 Apr; 7(2):222-230.  View on PubMed
  19. 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
  20. 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

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