Zhiqing Huang

Overview:

Dr. Huang is an Assistant Professor in the Department of Obstetrics and Gynecology, Division of Reproductive Sciences, at Duke University Medical Center. She obtained her MD at North China Coal Medical University in China and her PhD at the University of Heidelberg in Germany under the mentorship of Dr. Ralph Witzgall. She did her postdoctoral training with Dr. Jiemin Wong at Baylor College of Medicine, studying how histone methylation and chromatin modifications regulate androgen receptor transcription. Dr. Huang’s research is focused primarily on ovarian cancer, specifically, on the mechanisms and gene regulation of ovarian cancer recurrence and the impact of the tumor microenvironment on ovarian cancer recurrence. 

Positions:

Assistant Professor in Obstetrics and Gynecology

Obstetrics and Gynecology, Reproductive Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1985

North China Coal Medical College (China)

Grants:

Publications:

Male obesity impacts DNA methylation reprogramming in sperm.

BACKGROUND: Male obesity has profound effects on morbidity and mortality, but relatively little is known about the impact of obesity on gametes and the potential for adverse effects of male obesity to be passed to the next generation. DNA methylation contributes to gene regulation and is erased and re-established during gametogenesis. Throughout post-pubertal spermatogenesis, there are continual needs to both maintain established methylation and complete DNA methylation programming, even during epididymal maturation. This dynamic epigenetic landscape may confer increased vulnerability to environmental influences, including the obesogenic environment, that could disrupt reprogramming fidelity. Here we conducted an exploratory analysis that showed that overweight/obesity (n = 20) is associated with differences in mature spermatozoa DNA methylation profiles relative to controls with normal BMI (n = 47). RESULTS: We identified 3264 CpG sites in human sperm that are significantly associated with BMI (p < 0.05) using Infinium HumanMethylation450 BeadChips. These CpG sites were significantly overrepresented among genes involved in transcriptional regulation and misregulation in cancer, nervous system development, and stem cell pluripotency. Analysis of individual sperm using bisulfite sequencing of cloned alleles revealed that the methylation differences are present in a subset of sperm rather than being randomly distributed across all sperm. CONCLUSIONS: Male obesity is associated with altered sperm DNA methylation profiles that appear to affect reprogramming fidelity in a subset of sperm, suggestive of an influence on the spermatogonia. Further work is required to determine the potential heritability of these DNA methylation alterations. If heritable, these changes have the potential to impede normal development.
Authors
Keyhan, S; Burke, E; Schrott, R; Huang, Z; Grenier, C; Price, T; Raburn, D; Corcoran, DL; Soubry, A; Hoyo, C; Murphy, SK
MLA Citation
Keyhan, Sanaz, et al. “Male obesity impacts DNA methylation reprogramming in sperm.Clin Epigenetics, vol. 13, no. 1, Jan. 2021, p. 17. Pubmed, doi:10.1186/s13148-020-00997-0.
URI
https://scholars.duke.edu/individual/pub1472639
PMID
33494820
Source
pubmed
Published In
Clin Epigenetics
Volume
13
Published Date
Start Page
17
DOI
10.1186/s13148-020-00997-0

Gene Expression using Affymetrix Human Genome U133 Plus 2 Arrays from 16 Primary and Recurrent Serous Epithelial Ovarian Cancers

This dataset was generated from 16 primary and matched recurrent ovarian cancer tissue sets from patients with stage III/IV serous epithelial ovarian cancer who were treated at Duke University Medical Center in Durham, North Carolina. The primary tumor specimens were collected at the time of initial debulking surgery. Recurrent tumor samples were obtained from the same patients during "second-look" surgeries. Samples were obtained and data was generated after patients provided written informed consent under protocols approved by the Duke University Institutional Review Board. Tumor specimens were stored at -80ºC until nucleic acid extraction.
Authors
Murphy, S; Whitaker, R; Sfakianos, G; Berchuck, A; Huang, Z
URI
https://scholars.duke.edu/individual/pub1472966
Source
manual
Published Date
DOI
10.7924/r43f4sx2k

Primary and recurrent (second-look surgery) serous epithelial ovarian cancers Illumina Infinium HumanMethylation450 BeadChip data

This dataset was generated from 16 primary and matched recurrent ovarian cancer tissue sets from patients with stage III/IV serous epithelial OC. The primary tumor specimens were collected at the time of initial debulking surgery. Recurrent tumor samples were obtained from the same patients during “second-look” surgeries. Samples were obtained and data was generated after patients provided written informed consent under protocols approved by the Duke University Institutional Review Board.
Authors
Murphy, S; Sfakianos, G; Whitaker, R; Berchuk, A; Huang, Z
URI
https://scholars.duke.edu/individual/pub1470521
Source
manual
Published Date
DOI
10.7924/r4765hq57

Targeting Dormant Ovarian Cancer Cells In Vitro and in an In Vivo Mouse Model of Platinum Resistance.

Spheroids exhibit drug resistance and slow proliferation, suggesting involvement in cancer recurrence. The protein kinase C inhibitor UCN-01 (7-hydroxystaurosporine) has shown higher efficacy against slow proliferating and/or quiescent ovarian cancer cells. In this study, tumorigenic potential was assessed using anchorage-independent growth assays and spheroid-forming capacity, which was determined with ovarian cancer cell lines as well as primary ovarian cancers. Of 12 cell lines with increased anchorage-independent growth, 8 formed spheroids under serum-free culture conditions. Spheroids showed reduced proliferation (P < 0.0001) and Ki-67 immunostaining (8% vs. 87%) relative to monolayer cells. Spheroid formation was associated with increased expression of mitochondrial pathway genes (P ≤ 0.001) from Affymetrix HT U133A gene expression data. UCN-01, a kinase inhibitor/mitochondrial uncoupler that has been shown to lead to Puma-induced mitochondrial apoptosis as well as ATP synthase inhibitor oligomycin, demonstrated effectiveness against spheroids, whereas spheroids were refractory to cisplatin and paclitaxel. By live in vivo imaging, ovarian cancer xenograft tumors were reduced after primary treatment with carboplatin. Continued treatment with carboplatin was accompanied by an increase in tumor signal, whereas there was little or no increase in tumor signal observed with subsequent treatment with UCN-01 or oltipraz. Taken together, our findings suggest that genes involved in mitochondrial function in spheroids may be an important therapeutic target in preventing disease recurrence.
Authors
Huang, Z; Kondoh, E; Visco, ZR; Baba, T; Matsumura, N; Dolan, E; Whitaker, RS; Konishi, I; Fujii, S; Berchuck, A; Murphy, SK
MLA Citation
Huang, Zhiqing, et al. “Targeting Dormant Ovarian Cancer Cells In Vitro and in an In Vivo Mouse Model of Platinum Resistance.Mol Cancer Ther, vol. 20, no. 1, Jan. 2021, pp. 85–95. Pubmed, doi:10.1158/1535-7163.MCT-20-0119.
URI
https://scholars.duke.edu/individual/pub1462351
PMID
33037137
Source
pubmed
Published In
Mol Cancer Ther
Volume
20
Published Date
Start Page
85
End Page
95
DOI
10.1158/1535-7163.MCT-20-0119

Epigenetic Regulation of Claudin-1 in the Development of Ovarian Cancer Recurrence and Drug Resistance.

Over 21,000 women are diagnosed with ovarian cancer (OC) in the United States each year and over half that number succumb to this disease annually, often due to recurrent disease. A deeper understanding of the molecular events associated with recurrent disease is needed to identify potential targets. Using genome-scale DNA methylation and gene expression data for 16 matched primary-recurrent advanced stage serous epithelial OCs, we discovered that Claudin-1 (CLDN1), a tight junction protein, shows a stronger correlation between expression and methylation in recurrent versus primary OC at multiple CpG sites (R= -0.47 to -0.64 versus R= -0.32 to -0.57, respectively). An independent dataset showed that this correlation is stronger in tumors from short-term (<3y) survivors than in tumors from long-term (>7y) survivors (R= -0.41 to -0.46 versus R= 0.06 to -0.19, respectively). The presence of this inverse correlation in short-term survivors and recurrent tumors suggests an important role for this relationship and potential predictive value for disease prognosis. CLDN1 expression increased following pharmacologic inhibition of DNA methyltransferase activity (p< 0.001), thus validating the role of methylation in CLDN1 gene inhibition. CLDN1 knockdown enhanced chemosensitivity and suppressed cell proliferation, migration, and wound healing (p< 0.05). Stable CLDN1 knockdown in vivo resulted in reduced xenograft tumor growth but did not reach significance. Our results indicate that the relationship between CLDN1 methylation and expression plays an important role in OC aggressiveness and recurrence.
Authors
Visco, ZR; Sfakianos, G; Grenier, C; Boudreau, M-H; Simpson, S; Rodriguez, I; Whitaker, R; Yao, DY; Berchuck, A; Murphy, SK; Huang, Z
MLA Citation
Visco, Zachary R., et al. “Epigenetic Regulation of Claudin-1 in the Development of Ovarian Cancer Recurrence and Drug Resistance.Front Oncol, vol. 11, 2021, p. 620873. Pubmed, doi:10.3389/fonc.2021.620873.
URI
https://scholars.duke.edu/individual/pub1478069
PMID
33828978
Source
pubmed
Published In
Frontiers in Oncology
Volume
11
Published Date
Start Page
620873
DOI
10.3389/fonc.2021.620873