Qing Cheng

Overview:

My research has been focusing on the development of methodologies and strategies to address the general question of human cancer heterogeneity and complexity, recognizing that clinical outcomes reflect a combination of contribution from the actual tumor but also the environment in which the tumor resides. By understanding who is at risk for recurrence, who is likely to respond to a given agent or regimen, and who is likely to exhibit an adverse event associated with a particular therapy, it will be possible to tailor therapeutic strategies to the characteristics of the individual patient as opposed to relying on the results of studies with heterogeneous populations of patients.

I made the original observation that gene copy number alterations (CNAs) in malignant cells can quantitatively affect gene function (Nat Genet 2005), and the contribution of this work to the field of cancer pharmacogenomics and personalized medicine was highly recognized by a "NEWS AND VIEWS" paper of Nature Genetics, in 2005. I demonstrated that clinical phenotypes can be affected by multiple forms of alterations (methylation, mutation, CNA) (Am J Hum Genet 2006), and genome-scan of CNAs followed by pathway analysis could uncover the novel gene interactions (Nat Med 2011). We developed a methodology that compiled a large collection of genomic data (Breast Cancer Res 2012) and demonstrated that uniquely characteristic of a clinical phenotype, such as dormancy, could be accessed using gene signature, a collection of multiple genetic alterations (Breast Cancer Res 2014).

Positions:

Associate Professor in Surgery

Surgery, Surgical Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2001

National University of Singapore

Postdoctoral Research Associate

St. Jude Children's Research Hospital

Grants:

Publications:

Erratum: Epigenetic regulation of human γ-glutamyl hydrolase activity in acute lymphoblastic leukemia cells (The American Journal of Human Genetics (2006) 79 (264-274))

Authors
Cheng, Q; Cheng, C; Crews, KR; Ribeiro, RC; Pui, CH; Relling, MV; Evans, WE
MLA Citation
Cheng, Q., et al. “Erratum: Epigenetic regulation of human γ-glutamyl hydrolase activity in acute lymphoblastic leukemia cells (The American Journal of Human Genetics (2006) 79 (264-274)).” American Journal of Human Genetics, vol. 87, no. 1, July 2010, p. 161. Scopus, doi:10.1016/j.ajhg.2010.06.011.
URI
https://scholars.duke.edu/individual/pub749749
Source
scopus
Published In
American Journal of Human Genetics
Volume
87
Published Date
Start Page
161
DOI
10.1016/j.ajhg.2010.06.011

Synapsin IIa controls the reserve pool of glutamatergic synaptic vesicles.

Synapsins regulate synaptic transmission by controlling the reserve pool of synaptic vesicles. Each of the three mammalian synapsin genes is subject to alternative splicing, yielding several isoforms whose roles are unknown. To investigate the function of these isoforms, we examined the synaptic effects of introducing each isoform into glutamatergic cultured hippocampal neurons from synapsin triple knock-out mice. Remarkably, we found that synapsin IIa was the only isoform that could rescue the synaptic depression phenotype of the triple knock-out mice; other isoforms examined, including the well-studied synapsin Ia isoform, had no significant effect on the kinetics of synaptic depression. The slowing of synaptic depression by synapsin IIa was quantitatively paralleled by an increase in the density of reserve pool synaptic vesicles, as measured either by fluorescent tagging of the vesicle protein synaptobrevin-2 or by staining with the styryl dye FM4-64 [N-(3-triethylammoniumpropyl)-4-(6-(4-diethylamino)phenyl)-hexatrienyl)pyridinium dibromide]. Our results provide further support for the hypothesis that synapsins define the kinetics of synaptic depression at glutamatergic synapses by controlling the size of the vesicular reserve pool and identify synapsin IIa as the isoform primarily responsible for this task.
Authors
Gitler, D; Cheng, Q; Greengard, P; Augustine, GJ
MLA Citation
Gitler, Daniel, et al. “Synapsin IIa controls the reserve pool of glutamatergic synaptic vesicles.J Neurosci, vol. 28, no. 43, Oct. 2008, pp. 10835–43. Pubmed, doi:10.1523/JNEUROSCI.0924-08.2008.
URI
https://scholars.duke.edu/individual/pub810447
PMID
18945891
Source
pubmed
Published In
Journal of Neuroscience
Volume
28
Published Date
Start Page
10835
End Page
10843
DOI
10.1523/JNEUROSCI.0924-08.2008

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

Calcium channel modulation as an all-purpose mechanism for short-term synaptic plasticity.

The paper by Mochida et al. in this issue of Neuron proposes that synaptic facilitation, depression, and augmentation all arise from calcium-dependent regulation of calcium channels in the presynaptic terminal. Their proposal provides a unifying explanation for several forms of short-term presynaptic plasticity.
Authors
Cheng, Q; Augustine, GJ
MLA Citation
Cheng, Qing, and George J. Augustine. “Calcium channel modulation as an all-purpose mechanism for short-term synaptic plasticity.Neuron, vol. 57, no. 2, Jan. 2008, pp. 171–72. Epmc, doi:10.1016/j.neuron.2008.01.004.
URI
https://scholars.duke.edu/individual/pub810453
PMID
18215614
Source
epmc
Published In
Neuron
Volume
57
Published Date
Start Page
171
End Page
172
DOI
10.1016/j.neuron.2008.01.004

Cajal-Retzius cells switch from expressing gamma-less to gamma-containing GABA receptors during corticogenesis.

Cajal-Retzius cells are implicated in regulating neuronal migration and lamination during corticogenesis. In rodents, Cajal-Retzius cells are transient, being prevalent in the marginal zone of the embryonic neocortex and declining over the first two postnatal weeks. While studies have examined in postnatal neocortex the properties of GABA(A) receptors in Cajal-Retzius cells, less is known about their disposition at embryonic stages. Here, we combined patch-clamp electrophysiology and single-cell mRNA profiling to probe the expression of GABA(A) receptors in Cajal-Retzius cells. In embryonic neocortical slices, GABA elicited GABA(A) receptor-mediated current responses that were diazepam-insensitive and inhibited by Zn(2+), a pharmacological profile consistent with expression of gamma-less GABA(A) receptor isoforms. Non-Cajal-Retzius cells in the same embryonic slices, on the other hand, were robustly potentiated by diazepam and were insensitive to Zn(2+), typical of gamma-containing GABA(A) receptor isoforms, as were Cajal-Retzius cells in the postnatal neocortex. Single-cell mRNA profiling and immunohistochemistry confirmed expression of GABA(A) receptor gamma subunit transcript and protein, respectively, in individual reelin-expressing cells in the postnatal cortex but not in their embryonic counterparts. We conclude that Cajal-Retzius cells express gamma-less GABA(A) receptors at embryonic stages and switch to expressing gamma-containing GABA(A) receptor isoforms during postnatal neocortical development.
Authors
Cheng, Q; Yeh, PWL; Yeh, HH
MLA Citation
Cheng, Qing, et al. “Cajal-Retzius cells switch from expressing gamma-less to gamma-containing GABA receptors during corticogenesis.Eur J Neurosci, vol. 24, no. 8, Oct. 2006, pp. 2145–51. Pubmed, doi:10.1111/j.1460-9568.2006.05122.x.
URI
https://scholars.duke.edu/individual/pub870469
PMID
17074040
Source
pubmed
Published In
The European Journal of Neuroscience
Volume
24
Published Date
Start Page
2145
End Page
2151
DOI
10.1111/j.1460-9568.2006.05122.x