Takuya Osada

Positions:

Associate Professor of Surgery

Surgery, Surgical Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1986

University of Tokyo (Japan)

Ph.D. 1997

University of Tokyo (Japan)

Grants:

Targeting hCG-beta for Breast Cancer Immunotherapy

Administered By
Duke Cancer Institute
Awarded By
National Institutes of Health
Role
Research Analyst
Start Date
End Date

Dendritic Cell Mobilization and Active Immunotherapy

Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

Redirecting Specificity of Viral Specific T Cells

Awarded By
National Institutes of Health
Role
Research Scientist
Start Date
End Date

Publications:

Heat shock protein 90-targeted photodynamic therapy enables treatment of subcutaneous and visceral tumors.

Photodynamic therapy (PDT) ablates malignancies by applying focused near-infrared (nIR) light onto a lesion of interest after systemic administration of a photosensitizer (PS); however, the accumulation of existing PS is not tumor-exclusive. We developed a tumor-localizing strategy for PDT, exploiting the high expression of heat shock protein 90 (Hsp90) in cancer cells to retain high concentrations of PS by tethering a small molecule Hsp90 inhibitor to a PS (verteporfin, VP) to create an Hsp90-targeted PS (HS201). HS201 accumulates to a greater extent than VP in breast cancer cells both in vitro and in vivo, resulting in increased treatment efficacy of HS201-PDT in various human breast cancer xenografts regardless of molecular and clinical subtypes. The therapeutic index achieved with Hsp90-targeted PDT would permit treatment not only of localized tumors, but also more diffusely infiltrating processes such as inflammatory breast cancer.
Authors
Kaneko, K; Osada, T; Morse, MA; Gwin, WR; Ginzel, JD; Snyder, JC; Yang, X-Y; Liu, C-X; Diniz, MA; Bodoor, K; Hughes, PF; Haystead, TA; Lyerly, HK
MLA Citation
Kaneko, Kensuke, et al. “Heat shock protein 90-targeted photodynamic therapy enables treatment of subcutaneous and visceral tumors.Commun Biol, vol. 3, no. 1, May 2020, p. 226. Pubmed, doi:10.1038/s42003-020-0956-7.
URI
https://scholars.duke.edu/individual/pub1441154
PMID
32385408
Source
pubmed
Published In
Communications Biology
Volume
3
Published Date
Start Page
226
DOI
10.1038/s42003-020-0956-7

Abstract 4071: A novel combination therapy of high intensity focused ultrasound and PDL1 blockades against advanced breast cancer

Authors
Abe, S; Osada, T; Kaneko, K; Zhong, P; Lyerly, HK
MLA Citation
Abe, Shinya, et al. “Abstract 4071: A novel combination therapy of high intensity focused ultrasound and PDL1 blockades against advanced breast cancer.” Immunology, American Association for Cancer Research, 2019. Crossref, doi:10.1158/1538-7445.am2019-4071.
URI
https://scholars.duke.edu/individual/pub1416574
Source
crossref
Published In
Immunology
Published Date
DOI
10.1158/1538-7445.am2019-4071

Abstract 3731: A novel heat shock protein 90-targeted photosensitizer (HS-201) enables enhanced tumor-specific photodynamic therapy of inflammatory breast cancers

Authors
Kaneko, K; Osada, T; Hughes, PF; Haystead, TA; Morse, MA; Lyerly, HK
MLA Citation
Kaneko, Kensuke, et al. “Abstract 3731: A novel heat shock protein 90-targeted photosensitizer (HS-201) enables enhanced tumor-specific photodynamic therapy of inflammatory breast cancers.” Tumor Biology, American Association for Cancer Research, 2019. Crossref, doi:10.1158/1538-7445.am2019-3731.
URI
https://scholars.duke.edu/individual/pub1417346
Source
crossref
Published In
Tumor Biology
Published Date
DOI
10.1158/1538-7445.am2019-3731

Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients

Authors
Crosby, EJ; Gwin, WR; Chang, S; Maecker, HT; Lubkov, V; Snyder, JC; Broadwater, G; Hyslop, T; Osada, T; Hobeika, AC; Hartman, ZC; Morse, MA; Lyerly, HK
MLA Citation
Crosby, E. J., et al. “Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients.” Poster Session Abstracts, American Association for Cancer Research, 2019. Crossref, doi:10.1158/1538-7445.sabcs18-p2-09-16.
URI
https://scholars.duke.edu/individual/pub1404161
Source
crossref
Published In
Poster Session Abstracts
Published Date
DOI
10.1158/1538-7445.sabcs18-p2-09-16

Niclosamide-induced Wnt signaling inhibition in colorectal cancer is mediated by autophagy.

The Wnt signaling pathway, known for regulating genes critical to normal embryonic development and tissue homeostasis, is dysregulated in many types of cancer. Previously, we identified that the anthelmintic drug niclosamide inhibited Wnt signaling by promoting internalization of Wnt receptor Frizzled 1 and degradation of Wnt signaling pathway proteins, Dishevelled 2 and β-catenin, contributing to suppression of colorectal cancer growth in vitro and in vivo Here, we provide evidence that niclosamide-mediated inhibition of Wnt signaling is mediated through autophagosomes induced by niclosamide. Specifically, niclosamide promotes the co-localization of Frizzled 1 or β-catenin with LC3, an autophagosome marker. Niclosamide inhibition of Wnt signaling is attenuated in autophagosome-deficient ATG5-/- MEF cells or cells expressing shRNA targeting Beclin1, a critical constituent of autophagosome. Treatment with the autophagosome inhibitor 3MA blocks niclosamide-mediated Frizzled 1 degradation. The sensitivity of colorectal cancer cells to growth inhibition by niclosamide is correlated with autophagosome formation induced by niclosamide. Niclosamide inhibits mTORC1 and ULK1 activities and induces LC3B expression in niclosamide-sensitive cell lines, but not in the niclosamide-resistant cell lines tested. Interestingly, niclosamide is a less effective inhibitor of Wnt-responsive genes (β-catenin, c-Myc, and Survivin) in the niclosamide-resistant cells than in the niclosamide-sensitive cells, suggesting that deficient autophagy induction by niclosamide compromises the effect of niclosamide on Wnt signaling. Our findings provide a mechanistic understanding of the role of autophagosomes in the inhibition of Wnt signaling by niclosamide and may provide biomarkers to assist selection of patients whose tumors are likely to respond to niclosamide.
Authors
Wang, J; Ren, X-R; Piao, H; Zhao, S; Osada, T; Premont, RT; Mook, RA; Morse, MA; Lyerly, HK; Chen, W
MLA Citation
Wang, Jiangbo, et al. “Niclosamide-induced Wnt signaling inhibition in colorectal cancer is mediated by autophagy.Biochem J, vol. 476, no. 3, Feb. 2019, pp. 535–46. Pubmed, doi:10.1042/BCJ20180385.
URI
https://scholars.duke.edu/individual/pub1364539
PMID
30635359
Source
pubmed
Published In
The Biochemical Journal
Volume
476
Published Date
Start Page
535
End Page
546
DOI
10.1042/BCJ20180385