Jiaoti Huang

Overview:

I am a physician-scientist with clinical expertise in the pathologic diagnosis of genitourinary tumors including tumors of the prostate, bladder, kidney and testis. Another area of interest is gynecologic tumors. In my research laboratory we study prostate cancer, focusing on molecular mechanisms of carcinogenesis and tumor progression, as well as biomarkers, imaging and novel therapeutic strategies. In addition to patient care and research, I am also passionate about education. I have trained numerous residents, fellows, graduate students and postdocs.

Positions:

Endowed Department Chair of Pathology

Pathology
School of Medicine

Professor of Pathology

Pathology
School of Medicine

Chair

Pathology
School of Medicine

Professor of Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Professor of Cell Biology

Cell Biology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1983

Anhui Medical University (China)

Ph.D. 1991

New York University

Grants:

Histologic and Immunohistochemical Biomarkers for Heavily Treated Metastatic Prostate Cancer

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

A novel strategy to identify prostate cancer biomarkers for patient management

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Stand Up 2 Cancer West Coast Dream Team Grant

Administered By
Pathology
Awarded By
University of San Francisco
Role
Principal Investigator
Start Date
End Date

Confirmation of histologic SCNC (NEPC)

Administered By
Pathology
Awarded By
BioXcel Therapeutics
Role
Principal Investigator
Start Date
End Date

Assessment of macrophage density in historical tNEPC tissue samples.

Administered By
Pathology
Awarded By
BioXcel Therapeutics
Role
Principal Investigator
Start Date
End Date

Publications:

Immunotherapeutic targeting and PET imaging of DLL3 in small cell neuroendocrine prostate cancer.

Effective treatments for de novo and treatment-emergent small cell/neuroendocrine (t-SCNC) prostate cancer represent an unmet need for this disease. Using metastatic biopsies from advanced cancer patients, we demonstrate that delta-like ligand 3 (DLL3) is expressed in de novo and t-SCNC and is associated with reduced survival. We develop a positron-emission tomography (PET) agent, [89Zr]-DFO-DLL3-scFv, that detects DLL3 levels in mouse SCNC models. In multiple patient-derived xenograft models, AMG 757 (tarlatamab), a half-life-extended bispecific T cell engager (BiTE®) immunotherapy that redirects CD3-positive T cells to kill DLL3-expressing cells, exhibited potent and durable anti-tumor activity. Late relapsing tumors after AMG 757 treatment exhibited lower DLL3 levels, suggesting antigen loss as a resistance mechanism, particularly in tumors with heterogeneous DLL3 expression. These findings have been translated into an ongoing clinical trial of AMG 757 in de novo and t-SCNC, with a confirmed objective partial response in a patient with histologically confirmed SCNC. Overall, these results identify DLL3 as a therapeutic target in SCNC and demonstrate that DLL3-targeted BiTE® immunotherapy has significant anti-tumor activity in this aggressive prostate cancer subtype.
Authors
Chou, J; Egusa, EA; Wang, S; Badura, ML; Lee, F; Bidkar, AP; Zhu, J; Shenoy, T; Trepka, K; Robinson, TM; Steri, V; Huang, J; Wang, Y; Small, EJ; Chan, E; Stohr, BA; Ashworth, A; Delafontaine, B; Rottey, S; Cooke, KS; Hashemi Sadraei, N; Yu, B; Salvati, M; Bailis, JM; Feng, FY; Flavell, RR; Aggarwal, R
MLA Citation
Chou, Jonathan, et al. “Immunotherapeutic targeting and PET imaging of DLL3 in small cell neuroendocrine prostate cancer.Cancer Res, Nov. 2022. Pubmed, doi:10.1158/0008-5472.CAN-22-1433.
URI
https://scholars.duke.edu/individual/pub1556477
PMID
36351060
Source
pubmed
Published In
Cancer Res
Published Date
DOI
10.1158/0008-5472.CAN-22-1433

The 5-Hydroxymethylcytosine Landscape of Prostate Cancer.

UNLABELLED: Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first study integrating whole-genome 5hmC with DNA, 5mC, and transcriptome sequencing in clinical samples of benign, localized, and advanced prostate cancer. 5hmC is shown to mark activation of cancer drivers and downstream targets. Furthermore, 5hmC sequencing revealed profoundly altered cell states throughout the disease course, characterized by increased proliferation, oncogenic signaling, dedifferentiation, and lineage plasticity to neuroendocrine and gastrointestinal lineages. Finally, 5hmC sequencing of cell-free DNA from patients with metastatic disease proved useful as a prognostic biomarker able to identify an aggressive subtype of prostate cancer using the genes TOP2A and EZH2, previously only detectable by transcriptomic analysis of solid tumor biopsies. Overall, these findings reveal that 5hmC marks epigenomic activation in prostate cancer and identify hallmarks of prostate cancer progression with potential as biomarkers of aggressive disease. SIGNIFICANCE: In prostate cancer, 5-hydroxymethylcytosine delineates oncogene activation and stage-specific cell states and can be analyzed in liquid biopsies to detect cancer phenotypes. See related article by Wu and Attard, p. 3880.
Authors
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, X-L; Huang, J; Zwart, W; Gilbert, LA; Maher, CA; Boutros, PC; Chi, KN; Ashworth, A; Small, EJ; He, HH; Wyatt, AW; Quigley, DA; Feng, FY
MLA Citation
Sjöström, Martin, et al. “The 5-Hydroxymethylcytosine Landscape of Prostate Cancer.Cancer Res, vol. 82, no. 21, Nov. 2022, pp. 3888–902. Pubmed, doi:10.1158/0008-5472.CAN-22-1123.
URI
https://scholars.duke.edu/individual/pub1554124
PMID
36251389
Source
pubmed
Published In
Cancer Res
Volume
82
Published Date
Start Page
3888
End Page
3902
DOI
10.1158/0008-5472.CAN-22-1123

Potential therapeutic effect of epigenetic therapy on treatment-induced neuroendocrine prostate cancer.

Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model (LNCaP/NE1.8) to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy. We also studied the role of cancer stem cells in enhancing invasion in treatment-induced neuroendocrine prostate cancer cells that recurred after long-term androgen-ablation treatment. Using an in vitro system mimicking clinical androgen-ablation, our results showed that the neuroendocrine-like subclone NE1.8 cells were enriched with cancer stem cells. Compared to parental prostate adenocarcinoma LNCaP cells, NE1.8 cells are more resistant to androgen deprivation therapy and chemotherapeutic agents and show increased cancer cell invasiveness. Results from this study also suggest a potential epigenetic therapeutic strategy using suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, as a chemotherapeutic agent for therapy-resistant treatment-induced neuroendocrine prostate cancer cells to minimize the risk of prostate cancer recurrence and metastasis.
Authors
Xu, X; Huang, Y-H; Li, Y-J; Cohen, A; Li, Z; Squires, J; Zhang, W; Chen, X-F; Zhang, M; Huang, J-T
MLA Citation
Xu, Xiang, et al. “Potential therapeutic effect of epigenetic therapy on treatment-induced neuroendocrine prostate cancer.Asian J Androl, vol. 19, no. 6, 2017, pp. 686–93. Pubmed, doi:10.4103/1008-682X.191518.
URI
https://scholars.duke.edu/individual/pub1535126
PMID
27905327
Source
pubmed
Published In
Asian Journal of Andrology
Volume
19
Published Date
Start Page
686
End Page
693
DOI
10.4103/1008-682X.191518

Letter to the Editor: mRNA Vaccines in Urological Malignancies.

Authors
Yang, L; Gao, G; Huang, J
MLA Citation
Yang, Lu, et al. “Letter to the Editor: mRNA Vaccines in Urological Malignancies.Hum Gene Ther, vol. 33, no. 19–20, Oct. 2022, pp. 1101–02. Pubmed, doi:10.1089/hum.2022.29218.lya.
URI
https://scholars.duke.edu/individual/pub1555209
PMID
36282986
Source
pubmed
Published In
Hum Gene Ther
Volume
33
Published Date
Start Page
1101
End Page
1102
DOI
10.1089/hum.2022.29218.lya

Histone methyltransferase SETDB1 is required for prostate cancer cell proliferation, migration and invasion.

SETDB1 has been established as an oncogene in a number of human carcinomas. The present study was to evaluate the expression of SETDB1 in prostate cancer (PCa) tissues and cells and to preliminarily investigate the role of SETDB1 in prostate tumorigenesis in vitro. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to detect the expression of SETDB1 in PCa tissues, adjacent normal tissues, benign prostatic hyperplasia (BPH) tissues, PCa cell lines and normal prostate epithelial cells. The results suggested that SETDB1 was upregulated in human PCa tissues compared with normal tissues at the mRNA and protein levels. The role of SETDB1 in proliferation was analyzed with cell counting kit-8, colony-forming efficiency and flow cytometry assays. The results indicated that downregulation of SETDB1 by siRNA inhibited PCa cell growth, and induced G0/G1 cell cycle arrest. The PCa cell migration and invasion decreased by silcencing SETDB1 which were assessed by using in vitro scratch and transwell invasion assay respectively. Our data suggested that SETDB1 is overexpressed in human PCa. Silencing SETDB1 inhibited PCa cell proliferation, migration and invasion.
Authors
Sun, Y; Wei, M; Ren, S-C; Chen, R; Xu, W-D; Wang, F-B; Lu, J; Shen, J; Yu, Y-W; Hou, J-G; Xu, C-L; Huang, J-T; Sun, Y-H
MLA Citation
Sun, Yi, et al. “Histone methyltransferase SETDB1 is required for prostate cancer cell proliferation, migration and invasion.Asian J Androl, vol. 16, no. 2, 2014, pp. 319–24. Pubmed, doi:10.4103/1008-682X.122812.
URI
https://scholars.duke.edu/individual/pub1535127
PMID
24556744
Source
pubmed
Published In
Asian Journal of Andrology
Volume
16
Published Date
Start Page
319
End Page
324
DOI
10.4103/1008-682X.122812