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

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:

Neuroendocrine cells of the prostate: Histology, biological functions, and molecular mechanisms.

Prostate cancer (PCa) is a common cause of cancer-related mortality in men worldwide. Although most men are diagnosed with low grade, indolent tumors that are potentially curable, a significant subset develops advanced disease where hormone therapy is required to target the androgen receptor (AR). Despite its initial effect, hormone therapy eventually fails and the tumor progresses to lethal stages even through continued inhibition of AR. This review article focuses on the role of PCa cellular heterogeneity in therapy resistance and disease progression. Although AR-positive luminal-type cells represent the vast majority of PCa cells, there exists a minor component of AR-negative neuroendocrine (NE) cells that are resistant to hormonal therapy and are enriched by the treatment. In addition, it is now well accepted that a significant subset of hormonally treated tumors recur as small cell neuroendocrine carcinoma (SCNC), further highlighting the importance of targeting NE cells in addition to the more abundant luminal-type cancer cells. Although it has been long recognized that NE cells are present in PCa, their underlying function in benign prostate and molecular mechanisms contributing to PCa progression remains poorly understood. In this article, we review the morphology and function of NE cells in benign prostate and PCa as well as underlying molecular mechanisms. In addition, we review the major reported mechanisms for transformation from common adenocarcinoma histology to the highly lethal SCNC, a significant clinical challenge in the management of advanced PCa.
Authors
Butler, W; Huang, J
MLA Citation
Butler, William, and Jiaoti Huang. “Neuroendocrine cells of the prostate: Histology, biological functions, and molecular mechanisms.Precis Clin Med, vol. 4, no. 1, Mar. 2021, pp. 25–34. Pubmed, doi:10.1093/pcmedi/pbab003.
URI
https://scholars.duke.edu/individual/pub1472995
PMID
33842835
Source
pubmed
Published In
Precis Clin Med
Volume
4
Published Date
Start Page
25
End Page
34
DOI
10.1093/pcmedi/pbab003

Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study.

<jats:p> 89 </jats:p><jats:p> Background: Men with metastatic neuroendocrine/small cell and aggressive variant prostate cancer (NEPC/AVPC) have poor outcomes despite platinum and taxane chemotherapy. These tumors share common features with small cell lung cancer, including higher tumor mutational burden and genomic alterations, and thus may be responsive to immunotherapy. Methods: We conducted a single arm, 2-stage phase II investigator-sponsored trial, (PICK-NEPC, NCT03179410) with the PD-L1 inhibitor avelumab in patients with NEPC/AVPC. NEPC/AVPC was defined either by histologic criteria (neuroendocrine or small cell features) by central pathology review or by aggressive variant clinical criteria (prior progression on abiraterone or enzalutamide with liver metastasis, bulky radiographic progression and low PSA, or high serum LDH). Prior chemotherapy or hormonal therapy was allowed. Avelumab 10 mg/kg IV every 2 weeks was administered until progression or unacceptable toxicity with ongoing ADT. The primary endpoint was overall response rate (ORR) defined by modified PCWG3 and iRECIST criteria. Results: We consented 19 men with AVPC/NEPC, and 15 initiated treatment with avelumab. The median age was 71 (range 51-85), and 27% had neuroendocrine or small cell histology, while 73% met AVPC clinical criteria with adenocarcinoma histology. Men had received a median of two prior systemic therapies (range 1-3) including carboplatin (27%), docetaxel (73%), enzalutamide (67%), and abiraterone (47%). Median PSA was 54 ng/mL (range 0-393) and 73% had liver metastasis. The ORR by iRECIST was 6.7% (95% CI 0-32%) with 1 CR, 0 PRs, 3 (20%) with stable disease, and 11 (73%) with progressive disease. The patient with a CR had NEPC with a CNS metastasis that was found to be MSI-high/TMB-high due to a somatic MSH2 alteration; he finished 12 months of avelumab and maintains a durable CR and undetectable PSA 6 months after completing all therapy including ADT. Median radiographic progression free survival was 1.8 months (95% CI 1.6-2.0 mo) and median time on therapy was 56 days (range 28-356). Median overall survival was 7.4 mo (85% CI 2.8-12.5 mo). Two grade 3 adverse events (abdominal pain due to hepatic disease progression versus immune hepatitis and pericarditis), and one grade 4 (immune hepatitis) adverse event were attributed to avelumab with no grade 5 adverse events. Grade 1 or 2 infusion-related reactions were experienced by 9 (60%). Conclusions: PD-L1 inhibition with avelumab demonstrated limited clinical efficacy in men with metastatic NEPC/AVPC other than in those with MSI-high disease. Further research is needed into mechanisms of immune evasion in NEPC/AVPC to develop novel immunotherapies. Clinical trial information: NCT03179410. </jats:p>
Authors
Brown, LC; Halabi, S; Humeniuk, MS; Wu, Y; Oyekunle, T; Huang, J; Anand, M; Davies, C; Zhang, T; Harrison, MR; George, DJ; Armstrong, AJ
MLA Citation
Brown, Landon Carter, et al. “Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study.Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 89–89. Crossref, doi:10.1200/jco.2021.39.6_suppl.89.
URI
https://scholars.duke.edu/individual/pub1480300
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
89
End Page
89
DOI
10.1200/jco.2021.39.6_suppl.89

Tissue clearing techniques for three-dimensional optical imaging of intact human prostate and correlations with multi-parametric MRI.

BACKGROUND: Tissue clearing technologies have enabled remarkable advancements for in situ characterization of tissues and exploration of the three-dimensional (3D) relationships between cells, however, these studies have predominantly been performed in non-human tissues and correlative assessment with clinical imaging has yet to be explored. We sought to evaluate the feasibility of tissue clearing technologies for 3D imaging of intact human prostate and the mapping of structurally and molecularly preserved pathology data with multi-parametric volumetric MR imaging (mpMRI). METHODS: Whole-mount prostates were processed with either hydrogel-based CLARITY or solvent-based iDISCO. The samples were stained with a nuclear dye or fluorescently labeled with antibodies against androgen receptor, alpha-methylacyl coenzyme-A racemase, or p63, and then imaged with 3D confocal microscopy. The apparent diffusion coefficient and Ktrans maps were computed from preoperative mpMRI. RESULTS: Quantitative analysis of cleared normal and tumor prostate tissue volumes displayed differences in 3D tissue architecture, marker-specific cell staining, and cell densities that were significantly correlated with mpMRI measurements in this initial, pilot cohort. CONCLUSIONS: 3D imaging of human prostate volumes following tissue clearing is a feasible technique for quantitative radiology-pathology correlation analysis with mpMRI and provides an opportunity to explore functional relationships between cellular structures and cross-sectional clinical imaging.
Authors
Cipollari, S; Jamshidi, N; Du, L; Sung, K; Huang, D; Margolis, DJ; Huang, J; Reiter, RE; Kuo, MD
MLA Citation
Cipollari, Stefano, et al. “Tissue clearing techniques for three-dimensional optical imaging of intact human prostate and correlations with multi-parametric MRI.Prostate, vol. 81, no. 9, June 2021, pp. 521–29. Pubmed, doi:10.1002/pros.24129.
URI
https://scholars.duke.edu/individual/pub1480285
PMID
33876838
Source
pubmed
Published In
Prostate
Volume
81
Published Date
Start Page
521
End Page
529
DOI
10.1002/pros.24129

Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer.

Castration-resistant prostate cancer (CRPC) is a terminal disease and the molecular underpinnings of CRPC development need to be better understood in order to improve its treatment. Here, we report that a transcription factor Yin Yang 1 (YY1) is significantly overexpressed during prostate cancer progression. Functional and cistrome studies of YY1 uncover its roles in promoting prostate oncogenesis in vitro and in vivo, as well as sustaining tumor metabolism including the Warburg effect and mitochondria respiration. Additionally, our integrated genomics and interactome profiling in prostate tumor show that YY1 and bromodomain-containing proteins (BRD2/4) co-occupy a majority of gene-regulatory elements, coactivating downstream targets. Via gene loss-of-function and rescue studies and mutagenesis of YY1-bound cis-elements, we unveil an oncogenic pathway in which YY1 directly binds and activates PFKP, a gene encoding the rate-limiting enzyme for glycolysis, significantly contributing to the YY1-enforced Warburg effect and malignant growth. Altogether, this study supports a master regulator role for YY1 in prostate tumorigenesis and reveals a YY1:BRD2/4-PFKP axis operating in advanced prostate cancer with implications for therapy.
Authors
Xu, C; Tsai, Y-H; Galbo, PM; Gong, W; Storey, AJ; Xu, Y; Byrum, SD; Xu, L; Whang, YE; Parker, JS; Mackintosh, SG; Edmondson, RD; Tackett, AJ; Huang, J; Zheng, D; Earp, HS; Wang, GG; Cai, L
MLA Citation
Xu, Chenxi, et al. “Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer.Nucleic Acids Res, Apr. 2021. Pubmed, doi:10.1093/nar/gkab252.
URI
https://scholars.duke.edu/individual/pub1478094
PMID
33849067
Source
pubmed
Published In
Nucleic Acids Res
Published Date
DOI
10.1093/nar/gkab252

Long-chain fatty acyl-CoA synthetase 1 promotes prostate cancer progression by elevation of lipogenesis and fatty acid beta-oxidation.

Fatty acid metabolism is essential for the biogenesis of cellular components and ATP production to sustain proliferation of cancer cells. Long-chain fatty acyl-CoA synthetases (ACSLs), a group of rate-limiting enzymes in fatty acid metabolism, catalyze the bioconversion of exogenous or de novo synthesized fatty acids to their corresponding fatty acyl-CoAs. In this study, systematical analysis of ACSLs levels and the amount of fatty acyl-CoAs illustrated that ACSL1 were significantly associated with the levels of a broad spectrum of fatty acyl-CoAs, and were elevated in human prostate tumors. ACSL1 increased the biosynthesis of fatty acyl-CoAs including C16:0-, C18:0-, C18:1-, and C18:2-CoA, triglycerides and lipid accumulation in cancer cells. Mechanistically, ACSL1 modulated mitochondrial respiration, β-oxidation, and ATP production through regulation of CPT1 activity. Knockdown of ACSL1 inhibited the cell cycle, and suppressed the proliferation and migration of prostate cancer cells in vitro, and growth of prostate xenograft tumors in vivo. Our study implicates ACSL1 as playing an important role in prostate tumor progression, and provides a therapeutic strategy of targeting fatty acid metabolism for the treatment of prostate cancer.
Authors
Ma, Y; Zha, J; Yang, X; Li, Q; Zhang, Q; Yin, A; Beharry, Z; Huang, H; Huang, J; Bartlett, M; Ye, K; Yin, H; Cai, H
MLA Citation
Ma, Yongjie, et al. “Long-chain fatty acyl-CoA synthetase 1 promotes prostate cancer progression by elevation of lipogenesis and fatty acid beta-oxidation.Oncogene, vol. 40, no. 10, Mar. 2021, pp. 1806–20. Pubmed, doi:10.1038/s41388-021-01667-y.
URI
https://scholars.duke.edu/individual/pub1473567
PMID
33564069
Source
pubmed
Published In
Oncogene
Volume
40
Published Date
Start Page
1806
End Page
1820
DOI
10.1038/s41388-021-01667-y