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

Center for Cancer Research
National Cancer Institute

Building 37, Room 1056
Bethesda, MD 20892
240-760-6332
david.takeda@nih.gov

Lasker Clinical Research Scholar

Genitourinary Malignancies Branch

Head, Functional Genomics Section

RESEARCH SUMMARY

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

Cancer Genomics

Chromosome Biology

Prostate Cancer

Epigenetics

Functional Genomics

Chromatin

Research
Publications
Biography
Job Vacancies
Team
News
Lab Life
Alumni

Research

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.

Publications

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 ]

Genetic Determinants of chromatin reveal prostate cancer risk mediated by context-dependent gene regulation

Baca SC, Singler C, Zacharia S, Seo JH, Morova T, Hach F, Ding Y, Schwarz T, Flora Huang C, Anderson J, Fay AP, Kalita C, Groha S, Pomerantz MM, Wang V, Linder S, Sweeney CJ, Zwart W, Lack NA, Pasaniuc B, Takeda DY, Gusev A, Freedman ML.

Nature Genetics. 54(9): 1364-1375, 2022. [ Journal Article ]

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 ]

Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer

Baca SC, Takeda DY, Seo JH, Hwang J, Ku SY, Arafeh R, Arnoff T, Agarwal S, Bell C, O'Connor E, Qiu X, Alaiwi SA, Corona RI, Fonseca MAS, Giambartolomei C, Cejas P, Lim K, He M, Sheahan A, Nassar A, Berchuck JE, Brown L, Nguyen HM, Coleman IM, Kaipainen A, De Sarkar N, Nelson PS, Morrissey C, Korthauer K, Pomerantz MM, Ellis L, Pasaniuc B, Lawrenson K, Kelly K, Zoubeidi A, Hahn WC, Beltran H, Long HW, Brown M, Corey E, Freedman ML.

Nature Communications. Mar 30;12(1): 1979, 2021. [ Journal Article ]

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 ]

Biography

Lasker Clinical Research Scholar

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

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.

Job Vacancies

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Team

Postdoctoral Fellow (CRTA)

Aleksandra Adamovich , Ph.D.

Postdoctoral Fellow (Visiting)

Matan Arbel-Groissman, Ph.D.

Postdoctoral Fellow (Visiting)

Shin-Ai Lee, Ph.D.

Postdoctoral Fellow (Visiting)

Naimur Rahman, Ph.D.

Postdoctoral Fellow (Visiting)

Sonam Raj, Ph.D.

Postbaccalaureate Fellow (CRTA)

Caroline Tyndall

Postbaccalaureate Fellow (CRTA)

Anusha Bhatia

News

Newest Lasker Scholars Ready to Make Their Mark

Congratulations to the investigators who recently joined the ranks of the Lasker Clinical Research Scholars Program, NIH’s collaborative effort with the Albert and Mary Lasker Foundation to nurture the next generation of clinical researchers, including David Takeda, whose research focuses on treatment-resistant prostate cancer. Read More

Reprogramming Cancer

David Takeda, M.D., Ph.D. is laying the groundwork for a bold new approach to cancer therapy. He believes that manipulating epigenetics could also provide a powerful new pathway for combatting the disease. Instead of thinking about cancer in terms of the mutated genes that drive their abnormal growth and division, perhaps we can reprogram the cell’s state,” he explains. “A cancer cell is a cell that is no longer, say, a skin cell. It’s now a new type of cell that can grow unrestricted. Maybe we can epigenetically reprogram the cell and give it a set of instructions so that it turns into something else — something that you can treat. Read More