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:

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

Ambient GABA promotes cortical entry of tangentially migrating cells derived from the medial ganglionic eminence.

During corticogenesis, cells from the medial ganglionic eminence (MGE) migrate tangentially into the neocortical anlage. Here we report that gamma-aminobutyric acid (GABA), via GABAA receptors, regulates tangential migration. In embryonic telencephalic slices, bicuculline produced an outward current in migrating MGE-derived cells in the neocortex, suggesting the presence of and tonic activation by ambient GABA. Ambient GABA was also present in the MGE, although this required demonstration using as bioassay HEK293 cells expressing high-affinity alpha6/beta2/gamma2s recombinant GABAA receptors. The concentration of ambient GABA was 0.5+/-0.1 microM in both regions. MGE-derived cells before the corticostriate juncture (CSJ) were less responsive to GABA than those in the neocortex, and profiling of GABAA receptor subunit transcripts revealed different expression patterns in the MGE vis-à-vis the neocortex. These findings suggest a dynamic expression of GABAA receptor number or isoform as MGE-derived cells enter the neocortex and become tonically influenced by ambient GABA. Treatment with bicuculline or antibody against GABA did not affect migration of MGE-derived cells before the CSJ but decreased "crossing index," reflecting impeded migration past the CSJ into the neocortex. Treatment with diazepam or addition of exogenous GABA increased crossing index. We conclude that ambient GABA promotes cortical entry of tangentially migrating MGE-derived cells.
Authors
Cuzon, VC; Yeh, PW; Cheng, Q; Yeh, HH
MLA Citation
Cuzon, Verginia C., et al. “Ambient GABA promotes cortical entry of tangentially migrating cells derived from the medial ganglionic eminence.Cereb Cortex, vol. 16, no. 10, Oct. 2006, pp. 1377–88. Pubmed, doi:10.1093/cercor/bhj084.
URI
https://scholars.duke.edu/individual/pub870476
PMID
16339085
Source
pubmed
Published In
Cerebral Cortex (New York, N.Y. : 1991)
Volume
16
Published Date
Start Page
1377
End Page
1388
DOI
10.1093/cercor/bhj084

Kinetic properties of GABA rho1 homomeric receptors expressed in HEK293 cells.

The rho1 subunit of the ionotropic GABA receptors is thought to contribute to the formation of the GABA(C) receptors with pharmacological and physiological properties distinct from those of GABA(A) receptors. Previous characterization of this subunit expressed in the Xenopus oocytes revealed an ion channel with slow activation and deactivation and no desensitization, quite different from the properties of GABA(C) receptors observed in native cells. We expressed the human rho1 subunit in human embryonic kidney (HEK) 293 cells and quantitatively characterized the kinetic properties of these receptors using a rapid drug application device. The rho1 subunit expressed in HEK293 cells exhibited pharmacological and kinetic properties qualitatively identical to those described when rho1 was expressed in the oocytes. An apparent desensitizing current observed during a constant GABA application was determined to be secondary to an E(Cl) shift. Detailed kinetic analyses and parameter estimation for a five-state kinetic model revealed that the channel is best described by a set of rate constants with a notably faster GABA unbinding K(off) rate compared to the parameters proposed for the same subunit expressed in the oocytes. The same subunit expressed in hippocampal neurons showed activation and deactivation kinetics identical to the current characterized in HEK293 cells. The kinetic properties of rho1 subunit expressed in a nonoocyte model system may be better described quantitatively by the rate constants presented here.
Authors
Yang, J; Cheng, Q; Takahashi, A; Goubaeva, F
MLA Citation
Yang, Jay, et al. “Kinetic properties of GABA rho1 homomeric receptors expressed in HEK293 cells.Biophys J, vol. 91, no. 6, Sept. 2006, pp. 2155–62. Pubmed, doi:10.1529/biophysj.106.085431.
URI
https://scholars.duke.edu/individual/pub975077
PMID
16798806
Source
pubmed
Published In
Biophysical Journal
Volume
91
Published Date
Start Page
2155
End Page
2162
DOI
10.1529/biophysj.106.085431