David Takeda, M.D., Ph.D.

David Takeda, M.D., Ph.D.
Investigator
Laboratory of Genitourinary Cancer Pathogenesis
NIH Lasker Clinical Research Scholar
Head, Functional Genomics Section

Dr. Takeda’s research is focused on understanding the role of epigenetic reprogramming in disease progression by combining genomic and epigenomic profiling of patient samples with functional studies in model systems. Current areas of investigation include identifying noncoding drivers of castration-resistance in prostate cancer, interrogating regulatory elements using unbiased proteomic and genetic approaches, and therapeutic targeting of oncogenic transcriptional programs in genitourinary cancers.

Areas of Expertise

1) epigenetics, 2) functional genomics, 3) chromatin, 4) prostate cancer, 5) androgen receptor, 6) treatment resistance

Contact Info

David Takeda, M.D., Ph.D.
Center for Cancer Research
National Cancer Institute
Building 37, Room 1066
Bethesda, MD 20892
Ph: 240-760-7933
david.takeda@nih.gov

Using a combination of epigenomic profiling and functional genome editing, we recently described an enhancer of the androgen receptor (AR) that is activated and amplified in 80% of metastatic castration-resistant prostate cancer (CRPC). Understanding the mechanism by which this epigenetic activation occurs will have immediate implications for treating and/or preventing the development of CRPC. We are using proteomic and genetic approaches to identify the molecular processes required for enhancer activation during disease progression.

Resistance to the antiandrogen enzalutamide is accompanied by alterations in the enhancer landscape based on epigenetic profiling from tumor samples. In order to identify epigenetic drivers of enzalutamide resistance, we are systematically interrogating enhancers that are activated or decommissioned following development of drug resistance.

The presence of recurrent epigenetic alterations imply opportunities for therapeutic targeting of the cancer epigenome. We use functional genome-scale approaches to discover epigenetic vulnerabilities in tumors that serve as starting points to design novel treatment strategies to suppress oncogenic transcriptional programs.

NIH Scientific Focus Areas:
Cancer Biology, Cell Biology, Chromosome Biology, Genetics and Genomics, Molecular Biology and Biochemistry
View Dr. Takeda's Complete Bibliography at NCBI.

Selected Recent Publications

  1. A somatically acquired enhancer of the androgen receptor is a noncoding driver in advanced prostate cancer.
    Takeda DY*, Spisak S*, Seo JH, Bell C, O’Conner E, Korthauer K, Ribli D, Csabai I, Solymosi N, Szallasi Z, Stillman DR, Cejas P, Qiu X, Long H, Tisza V, Nuzzo PV, Rohanizadegan M, Pomerantz MM, Hahn WC, Freedman ML. (*co-first author)
    Cell. 174(2): 422-432, 2018. [ Journal Article ]
  2. Prostate cancer reactivates developmental epigenomic programs during metastatic progression.
    Pomerantz MM, Qiu X, Zhu Y, Takeda DY, Pan W, Baca SC, Gusev A, Korthauer KD, Severson TM, Ha G, Viswanathan SR, Seo JH, Nguyen HM, Zhang B, Pasaniuc B, Giambartolomei C, Alaiwi SA, Bell CA, O'Connor EP, Chabot MS, Stillman DR, Lis R, Font-Tello A, Li L, Cejas P, Bergman AM, Sanders J, van der Poel HG, Gayther SA, Lawrenson K, Fonseca MA, Reddy J, Corona RI, Martovetsky G, Egan B, Choueiri T, Ellis L, Garraway IP, Lee GM, Corey E, Long HW, Zwart W, Freedman ML
    Nature Genetics. 52(8): 790-799, 2020. [ Journal Article ]
  3. Mutational processes shape the landscape of TP53 mutations in human cancer.
    Giacomelli AO, Yang X, Linter RE, McFarland JM, Duby M, Kim J, Howard TP, Takeda DY, Ly SH, Kim E, Gannon HS, Hurhula B, Sharpe T, Goodale A, Fritchman B, Steelman S, Vazquez F, Tsherniak A, Aguirre AJ, Doench JG, Piccioni F, Roberts CW, Meyerson M, Getz G, Johannessen CM, Root DE, Hahn WC.
    Nature Genetics. 50(10): 1381-1387, 2018. [ Journal Article ]
  4. Binding of TMPRSS2-ERG to BAF Chromatin Remodeling Complexes Mediates Prostate Oncogenesis.
    Sandoval GJ, Pulice JL, Pakula H, Schenone M, Takeda DY, Pop M, Boulay G, Williamson KE, McBride MJ, Pan, J, St. Pierre R, Hartman E, Garraway LA, Carr SA, Rivera MN, Li Z, Ronco L, Hahn WC, Kadoch C.
    Molecular Cell. 71(4): 554-566, 2018. [ Journal Article ]
  5. The androgen receptor is extensively reprogrammed in human prostate tumorigenesis.
    Pomerantz MM*, Li F*, Takeda DY*, Lenci R, Chonkar A, Chabot M, Cejas P, Vazquez F, Cook J, Shivdasani RA, Bowden M, Lis R, Hahn WC, Kantoff PW, Brown M, Loda M, Long HW, Freedman ML. (*co-first author)
    Nature Genetics. 47(11): 1346-1351, 2015. [ Journal Article ]

Dr. Takeda was born and raised in Pearl City, HI, and graduated from Pomona College with a B.A. in chemistry. He received his M.D., Ph.D. from Harvard Medical School working in the laboratory of Anindya Dutta studying DNA replication. He completed residency training in internal medicine at Brigham and Women’s Hospital and a hematology/oncology fellowship at the Dana-Farber Cancer Institute in Boston, MA, where he conducted post-doctoral work with William Hahn at the Broad Institute in Cambridge, MA.

Name Position
Aleksandra Adamovich Ph.D. Postdoctoral Fellow (CRTA)
Ben Hauk Postbaccalaureate Fellow (CRTA)
Andre Kydd M.D., Ph.D. Postdoctoral Fellow (iCURE)
Shin-Ai Lee Ph.D. Postdoctoral Fellow (Visiting)
Cassandra Singler Postbaccalaureate Fellow (CRTA)