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:

Correction: Functional domain and motif analyses of androgen receptor coregulator ARA70 and its differential expression in prostate cancer.

Authors
Hu, Y-C; Yeh, S; Yeh, S-D; Sampson, ER; Huang, J; Li, P; Hsu, C-L; Ting, H-J; Lin, H-K; Wang, L; Kim, E; Ni, J; Chang, C
MLA Citation
Hu, Yueh-Chiang, et al. “Correction: Functional domain and motif analyses of androgen receptor coregulator ARA70 and its differential expression in prostate cancer.J Biol Chem, vol. 295, no. 50, Dec. 2020, p. 17382. Pubmed, doi:10.1074/jbc.AAC120.016763.
URI
https://scholars.duke.edu/individual/pub1535125
PMID
33310747
Source
pubmed
Published In
The Journal of Biological Chemistry
Volume
295
Published Date
Start Page
17382
DOI
10.1074/jbc.AAC120.016763

Novel technique for characterizing prostate cancer utilizing MRI restriction spectrum imaging: proof of principle and initial clinical experience with extraprostatic extension.

BACKGROUND: Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI). METHODS: We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique. RESULTS: 27 patients were evaluated, excluding one patient where distortion could not be performed. Preoperative standard MRI correctly identified extraprostatic the extension in two of the nine pT3 (22%) patients, whereas RSI-MRI identified EPE in eight of nine (89%) patients. RSI-MRI correctly identified pT2 disease in the remaining 18 patients. CONCLUSIONS: In this proof of principle study, we conclude that our novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging. Further translational studies of prostate RSI-MRI in the diagnosis and staging of PCa are indicated.
Authors
Rakow-Penner, RA; White, NS; Parsons, JK; Choi, HW; Liss, MA; Kuperman, JM; Schenker-Ahmed, N; Bartsch, H; Mattrey, RF; Bradley, WG; Shabaik, A; Huang, J; Margolis, DJA; Raman, SS; Marks, L; Kane, CJ; Reiter, RE; Karow, DS; Dale, AM
MLA Citation
Rakow-Penner, R. A., et al. “Novel technique for characterizing prostate cancer utilizing MRI restriction spectrum imaging: proof of principle and initial clinical experience with extraprostatic extension.Prostate Cancer Prostatic Dis, vol. 18, no. 1, Mar. 2015, pp. 81–85. Pubmed, doi:10.1038/pcan.2014.50.
URI
https://scholars.duke.edu/individual/pub1299167
PMID
25559097
Source
pubmed
Published In
Prostate Cancer Prostatic Dis
Volume
18
Published Date
Start Page
81
End Page
85
DOI
10.1038/pcan.2014.50

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