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:

DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study.

BACKGROUND: Maternal smoking during pregnancy is related to altered DNA methylation in infant umbilical cord blood. The extent to which low levels of smoke exposure among nonsmoking pregnant women relates to offspring DNA methylation is unknown. OBJECTIVE: This study sought to evaluate relationships between maternal prenatal plasma cotinine levels and DNA methylation in umbilical cord blood in newborns using the Infinium HumanMethylation 450K BeadChip. METHODS: Participants from the Newborn Epigenetics Study cohort who reported not smoking during pregnancy had verified low levels of cotinine from maternal prenatal plasma (0 ng/mL to <4 ng/mL), and offspring epigenetic data from umbilical cord blood were included in this study (n=79). Multivariable linear regression models were fit to the data, controlling for cell proportions, age, race, education, and parity. Estimates represent changes in response to any 1-ng/mL unit increase in exposure. RESULTS: Multivariable linear regression models yielded 29,049 CpGs that were differentially methylated in relation to increases in cotinine at a 5% false discovery rate. Top CpGs were within or near genes involved in neuronal functioning (PRKG1, DLGAP2, BSG), carcinogenesis (FHIT, HSPC157) and inflammation (AGER). Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest cotinine was related to methylation of gene pathways controlling neuronal signaling, metabolic regulation, cell signaling and regulation, and cancer. Further, enhancers associated with transcription start sites were enriched in altered CpGs. Using an independent sample from the same study population (n=115), bisulfite pyrosequencing was performed with infant cord blood DNA for two genes within our top 20 hits (AGER and PRKG1). Results from pyrosequencing replicated epigenome results for PRKG1 (cg17079497, estimate=-1.09, standard error (SE)=0.45, p=0.018) but not for AGER (cg09199225; estimate=-0.16, SE=0.21, p=0.44). DISCUSSION: Secondhand smoke exposure among nonsmoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation in distinct sites of mixed umbilical cord blood leukocytes in pathways that are known to be altered in cord blood from pregnant active smokers. https://doi.org/10.1289/EHP8099.
Authors
Fuemmeler, BF; Dozmorov, MG; Do, EK; Zhang, JJ; Grenier, C; Huang, Z; Maguire, RL; Kollins, SH; Hoyo, C; Murphy, SK
MLA Citation
Fuemmeler, Bernard F., et al. “DNA Methylation in Babies Born to Nonsmoking Mothers Exposed to Secondhand Smoke during Pregnancy: An Epigenome-Wide Association Study.Environ Health Perspect, vol. 129, no. 5, May 2021, p. 57010. Pubmed, doi:10.1289/EHP8099.
URI
https://scholars.duke.edu/individual/pub1483191
PMID
34009014
Source
pubmed
Published In
Environ Health Perspect
Volume
129
Published Date
Start Page
57010
DOI
10.1289/EHP8099

H2O2-Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways.

Mn(III) ortho-N-alkyl- and N-alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with numerous reactive species (such as ONOO-, H2O2, H2S, CO3 •-, ascorbate, and GSH). Moreover, the ability of MnPs to oxidatively modify activities of numerous proteins has emerged as their major mechanism of action both in normal and in cancer cells. Among those proteins are transcription factors (NF-κB and Nrf2), mitogen-activated protein kinases, MAPKs, antiapoptotic bcl-2, and endogenous antioxidative defenses. The lead Mn porphyrins, namely, MnTE-2-PyP5+ (BMX-010, AEOL10113), MnTnBuOE-2-PyP5+ (BMX-001), and MnTnHex-2-PyP5+, were tested in numerous injuries of normal tissue and cellular and animal cancer models. The wealth of the data led to the progression of MnTnBuOE-2-PyP5+ into four Phase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE-2-PyP5+ is in Phase II clinical trial on atopic dermatitis and itch.
Authors
Batinic-Haberle, I; Tovmasyan, A; Huang, Z; Duan, W; Du, L; Siamakpour-Reihani, S; Cao, Z; Sheng, H; Spasojevic, I; Alvarez Secord, A
MLA Citation
Batinic-Haberle, Ines, et al. “H2O2-Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways.Oxid Med Cell Longev, vol. 2021, 2021, p. 6653790. Pubmed, doi:10.1155/2021/6653790.
URI
https://scholars.duke.edu/individual/pub1478217
PMID
33815656
Source
pubmed
Published In
Oxid Med Cell Longev
Volume
2021
Published Date
Start Page
6653790
DOI
10.1155/2021/6653790

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