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

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

Role and targeting of PRMT5 in prostate cancer

Administered By
Pathology
Awarded By
Purdue University
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
Role
Principal Investigator
Start Date
End Date

Confirmation of histologic SCNC (NEPC)

Administered By
Pathology
Role
Principal Investigator
Start Date
End Date

Publications:

A genetically defined disease model reveals that urothelial cells can initiate divergent bladder cancer phenotypes.

Small cell carcinoma of the bladder (SCCB) is a rare and lethal phenotype of bladder cancer. The pathogenesis and molecular features are unknown. Here, we established a genetically engineered SCCB model and a cohort of patient SCCB and urothelial carcinoma samples to characterize molecular similarities and differences between bladder cancer phenotypes. We demonstrate that SCCB shares a urothelial origin with other bladder cancer phenotypes by showing that urothelial cells driven by a set of defined oncogenic factors give rise to a mixture of tumor phenotypes, including small cell carcinoma, urothelial carcinoma, and squamous cell carcinoma. Tumor-derived single-cell clones also give rise to both SCCB and urothelial carcinoma in xenografts. Despite this shared urothelial origin, clinical SCCB samples have a distinct transcriptional profile and a unique transcriptional regulatory network. Using the transcriptional profile from our cohort, we identified cell surface proteins (CSPs) associated with the SCCB phenotype. We found that the majority of SCCB samples have PD-L1 expression in both tumor cells and tumor-infiltrating lymphocytes, suggesting that immune checkpoint inhibitors could be a treatment option for SCCB. We further demonstrate that our genetically engineered tumor model is a representative tool for investigating CSPs in SCCB by showing that it shares a similar a CSP profile with clinical samples and expresses SCCB-up-regulated CSPs at both the mRNA and protein levels. Our findings reveal distinct molecular features of SCCB and provide a transcriptional dataset and a preclinical model for further investigating SCCB biology.
Authors
Wang, L; Smith, BA; Balanis, NG; Tsai, BL; Nguyen, K; Cheng, MW; Obusan, MB; Esedebe, FN; Patel, SJ; Zhang, H; Clark, PM; Sisk, AE; Said, JW; Huang, J; Graeber, TG; Witte, ON; Chin, AI; Park, JW
MLA Citation
Wang, Liang, et al. “A genetically defined disease model reveals that urothelial cells can initiate divergent bladder cancer phenotypes..” Proc Natl Acad Sci U S A, Dec. 2019. Pubmed, doi:10.1073/pnas.1915770117.
URI
https://scholars.duke.edu/individual/pub1424500
PMID
31871155
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Published Date
DOI
10.1073/pnas.1915770117

Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer.

Hormonal therapy targeting androgen receptor (AR) is initially effective to treat prostate cancer (PCa), but it eventually fails. It has been hypothesized that cellular heterogeneity of PCa, consisting of AR+ luminal tumor cells and AR- neuroendocrine (NE) tumor cells, may contribute to therapy failure. Here, we describe the successful purification of NE cells from primary fresh human prostate adenocarcinoma based on the cell surface receptor C-X-C motif chemokine receptor 2 (CXCR2). Functional studies revealed CXCR2 to be a driver of the NE phenotype, including loss of AR expression, lineage plasticity, and resistance to hormonal therapy. CXCR2-driven NE cells were critical for the tumor microenvironment by providing a survival niche for the AR+ luminal cells. We demonstrate that the combination of CXCR2 inhibition and AR targeting is an effective treatment strategy in mouse xenograft models. Such a strategy has the potential to overcome therapy resistance caused by tumor cell heterogeneity.
Authors
Li, Y; He, Y; Butler, W; Xu, L; Chang, Y; Lei, K; Zhang, H; Zhou, Y; Gao, AC; Zhang, Q; Taylor, DG; Cheng, D; Farber-Katz, S; Karam, R; Landrith, T; Li, B; Wu, S; Hsuan, V; Yang, Q; Hu, H; Chen, X; Flowers, M; McCall, SJ; Lee, JK; Smith, BA; Park, JW; Goldstein, AS; Witte, ON; Wang, Q; Rettig, MB; Armstrong, AJ; Cheng, Q; Huang, J
MLA Citation
Li, Yanjing, et al. “Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer..” Sci Transl Med, vol. 11, no. 521, Dec. 2019. Pubmed, doi:10.1126/scitranslmed.aax0428.
URI
https://scholars.duke.edu/individual/pub1423084
PMID
31801883
Source
pubmed
Published In
Sci Transl Med
Volume
11
Published Date
DOI
10.1126/scitranslmed.aax0428

LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer.

LRIG1 has been reported to be a tumor suppressor in gastrointestinal tract and epidermis. However, little is known about the expression, regulation and biological functions of LRIG1 in prostate cancer (PCa). We find that LRIG1 is overexpressed in PCa, but its expression correlates with better patient survival. Functional studies reveal strong tumor-suppressive functions of LRIG1 in both AR+ and AR- xenograft models, and transgenic expression of LRIG1 inhibits tumor development in Hi-Myc and TRAMP models. LRIG1 also inhibits castration-resistant PCa and exhibits therapeutic efficacy in pre-established tumors. We further show that 1) AR directly transactivates LRIG1 through binding to several AR-binding sites in LRIG1 locus, and 2) LRIG1 dampens ERBB expression in a cell type-dependent manner and inhibits ERBB2-driven tumor growth. Collectively, our study indicates that LRIG1 represents a pleiotropic AR-regulated feedback tumor suppressor that functions to restrict oncogenic signaling from AR, Myc, ERBBs, and, likely, other oncogenic drivers.
Authors
Li, Q; Liu, B; Chao, H-P; Ji, Y; Lu, Y; Mehmood, R; Jeter, C; Chen, T; Moore, JR; Li, W; Liu, C; Rycaj, K; Tracz, A; Kirk, J; Calhoun-Davis, T; Xiong, J; Deng, Q; Huang, J; Foster, BA; Gokhale, A; Chen, X; Tang, DG
MLA Citation
Li, Qiuhui, et al. “LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer..” Nat Commun, vol. 10, no. 1, Dec. 2019. Pubmed, doi:10.1038/s41467-019-13532-4.
URI
https://scholars.duke.edu/individual/pub1423359
PMID
31792211
Source
pubmed
Published In
Nature Communications
Volume
10
Published Date
Start Page
5494
DOI
10.1038/s41467-019-13532-4

Molecular determinants for enzalutamide-induced transcription in prostate cancer.

Enzalutamide, a second-generation androgen receptor (AR) antagonist, has demonstrated clinical benefit in men with prostate cancer. However, it only provides a temporary response and modest increase in survival, indicating a rapid evolution of resistance. Previous studies suggest that enzalutamide may function as a partial transcriptional agonist, but the underlying mechanisms for enzalutamide-induced transcription remain poorly understood. Here, we show that enzalutamide stimulates expression of a novel subset of genes distinct from androgen-responsive genes. Treatment of prostate cancer cells with enzalutamide enhances recruitment of pioneer factor GATA2, AR, Mediator subunits MED1 and MED14, and RNA Pol II to regulatory elements of enzalutamide-responsive genes. Mechanistically, GATA2 globally directs enzalutamide-induced transcription by facilitating AR, Mediator and Pol II loading to enzalutamide-responsive gene loci. Importantly, the GATA2 inhibitor K7174 inhibits enzalutamide-induced transcription by decreasing binding of the GATA2/AR/Mediator/Pol II transcriptional complex, contributing to sensitization of prostate cancer cells to enzalutamide treatment. Our findings provide mechanistic insight into the future combination of GATA2 inhibitors and enzalutamide for improved AR-targeted therapy.
Authors
MLA Citation
Yuan, Fuwen, et al. “Molecular determinants for enzalutamide-induced transcription in prostate cancer..” Nucleic Acids Res, vol. 47, no. 19, Nov. 2019, pp. 10104–14. Pubmed, doi:10.1093/nar/gkz790.
URI
https://scholars.duke.edu/individual/pub1409757
PMID
31501863
Source
pubmed
Published In
Nucleic Acids Res
Volume
47
Published Date
Start Page
10104
End Page
10114
DOI
10.1093/nar/gkz790

Morphologic Spectrum of Neuroendocrine Tumors of the Prostate: An Updated Review.

CONTEXT.—: The incidence of neuroendocrine tumors of the prostate increases after hormonal therapy. Neuroendocrine tumors possess a broad spectrum of morphologic features and pose challenges in the pathologic diagnosis and clinical management of patients. OBJECTIVE.—: To present a brief updated summary of neuroendocrine tumors of the prostate with an overview of their histopathologic and immunohistochemical profiles and differential diagnoses. DATA SOURCES.—: Literature review, personal experience in the daily practice of pathologic diagnosis, and laboratory research. CONCLUSIONS.—: Our understanding of neuroendocrine tumors of the prostate classification and diagnosis continues to evolve. These advances benefit the risk stratification and management of prostate cancer.
Authors
Hu, J; Han, B; Huang, J
MLA Citation
Hu, Jing, et al. “Morphologic Spectrum of Neuroendocrine Tumors of the Prostate: An Updated Review..” Arch Pathol Lab Med, Oct. 2019. Pubmed, doi:10.5858/arpa.2019-0434-RA.
URI
https://scholars.duke.edu/individual/pub1416550
PMID
31644322
Source
pubmed
Published In
Arch Pathol Lab Med
Published Date
DOI
10.5858/arpa.2019-0434-RA