Chanjuan Shi

Overview:

Dr. Shi is a gastrointestinal (GI)/liver pathologist. Her particular areas of interest are GI and pancreatic neuroendocrine tumors and pancreatic pathology. Her research interests include 1)  Pathobiology of GI and pancreatic neuroendocrine tumors and 2) Identification of diagnostic, prognostic and therapeutic biomarkers for colorectal and pancreatic cancers


Positions:

Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1989

Zhejiang University (China)

Ph.D. 2002

Dalhousie University (Canada)

Publications:

Lysophosphatidic acid receptor signaling in mammalian retinal pigment epithelial cells.

PURPOSE: Lysophosphatidic acid (LPA) is a phospholipid growth factor that stimulates proliferation, chemotaxis, cation currents, and K(+) currents in retinal pigment epithelial (RPE) cells. LPA receptor transduction was analyzed in human and rat RPE cells. METHODS: Cells were cultured with standard methods, and signaling pathways were analyzed with a variety of approaches, including whole-cell recording, calcium imaging, and second-messenger assays. RESULTS: LPA-activated nonselective cation currents in rat RPE were blocked by the protein tyrosine kinase (PTK) inhibitor genistein, by the MAP kinase kinase (MEK) inhibitor PD98059, and by loading cells with antibodies to G(alpha(i)/o/t/z). LPA activated the MAP kinase and extracellular signal-related kinase (ERK)-1, and produced a dose-dependent inhibition of cAMP production. LPA stimulated a dose-dependent increase in [Ca(2+)](i) that persisted in Ca(2+)-free medium and was reduced by pretreatment with thapsigargin, suggesting it involves release from intracellular stores. The [Ca(2+)](i) increase was not blocked by ryanodine or the phospholipase C inhibitor U73122. LPA did not stimulate inositol phosphate production. Similar to the cation current, LPA-evoked [Ca(2+)](i) increases were blocked by PD98059 and by loading cells with antibodies to G(alpha(i)/o/t/z). RT-PCR experiments showed the presence of RNA for three LPA receptor subtypes (Edg2, -4, and -7); RNase protection assays showed the strongest expression for Edg2 receptor RNA. CONCLUSIONS: LPA receptors in RPE cells activate pertussis toxin (PTx)-sensitive G proteins that inhibit cAMP accumulation; stimulate MAP kinase which activates a cation current and probably contributes to mitogenesis; and stimulate release of Ca(2+) from intracellular stores that appears independent of IP(3) and ryanodine receptor activation.
Authors
Thoreson, WB; Ryan, JS; Shi, C; Kelly, ME; Bryson, EJ; Toews, ML; Ediger, TL; Chacko, DM
MLA Citation
Thoreson, Wallace B., et al. “Lysophosphatidic acid receptor signaling in mammalian retinal pigment epithelial cells.Investigative Ophthalmology & Visual Science, vol. 43, no. 7, July 2002, pp. 2450–61.
URI
https://scholars.duke.edu/individual/pub1451815
PMID
12091450
Source
epmc
Published In
Investigative Ophthalmology & Visual Science
Volume
43
Published Date
Start Page
2450
End Page
2461

Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient?

Nivolumab is an immune checkpoint inhibitor (ICI) currently in phase 3 clinical trials for hepatocellular carcinoma. The safety of ICIs in recipients of organ allotransplant is unclear, and several reports of fatal alloimmune injury after posttransplant ICI use have been published. We present the first published case of nivolumab used in the pretransplant setting for HCC resulting in fatal acute hepatic necrosis in the immediate postoperative period from a profound immune reaction likely propagated by nivolumab. Further investigation and significant caution are needed in the evaluation of patients awaiting transplant who are receiving ICI therapy.
Authors
Nordness, MF; Hamel, S; Godfrey, CM; Shi, C; Johnson, DB; Goff, LW; O'Dell, H; Perri, RE; Alexopoulos, SP
MLA Citation
Nordness, Mina F., et al. “Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient?Am J Transplant, vol. 20, no. 3, Mar. 2020, pp. 879–83. Pubmed, doi:10.1111/ajt.15617.
URI
https://scholars.duke.edu/individual/pub1429372
PMID
31550417
Source
pubmed
Published In
Am J Transplant
Volume
20
Published Date
Start Page
879
End Page
883
DOI
10.1111/ajt.15617

Tobacco Carcinogen-Induced Production of GM-CSF Activates CREB to Promote Pancreatic Cancer.

Although smoking is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC), the molecular mechanisms underlying PDAC development and progression in smokers are still unclear. Here, we show the role of cyclic AMP response element-binding protein (CREB) in the pathogenesis of smoking-induced PDAC. Smokers had significantly higher levels of activated CREB when compared with nonsmokers. Cell lines derived from normal pancreas and pancreatic intraepithelial neoplasm (PanIN) exhibited low baseline pCREB levels compared with PDAC cell lines. Furthermore, elevated CREB expression correlated with reduced survival in patients with PDAC. Depletion of CREB significantly reduced tumor burden after tobacco-specific nitrosamine 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) treatment, suggesting a CREB-dependent contribution to PDAC growth and progression in smokers. Conversely, NNK accelerated PanIN lesion and PDAC formation via GM-CSF-mediated activation of CREB in a PDAC mouse model. CREB inhibition (CREBi) in mice more effectively reduced primary tumor burden compared with control or GM-CSF blockade alone following NNK exposure. GM-CSF played a role in the recruitment of tumor-associated macrophages (TAM) and regulatory T cell (Treg) expansion and promotion, whereas CREBi significantly reduced TAM and Treg populations in NNK-exposed mice. Overall, these results suggest that NNK exposure leads to activation of CREB through GM-CSF, promoting inflammatory and Akt pathways. Direct inhibition of CREB, but not GM-CSF, effectively abrogates these effects and inhibits tumor progression, offering a viable therapeutic strategy for patients with PDAC.Significance: These findings identify GM-CSF-induced CREB as a driver of pancreatic cancer in smokers and demonstrate the therapeutic potential of targeting CREB to reduce PDAC tumor growth.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/21/6146/F1.large.jpg Cancer Res; 78(21); 6146-58. ©2018 AACR.
Authors
Srinivasan, S; Totiger, T; Shi, C; Castellanos, J; Lamichhane, P; Dosch, AR; Messaggio, F; Kashikar, N; Honnenahally, K; Ban, Y; Merchant, NB; VanSaun, M; Nagathihalli, NS
MLA Citation
Srinivasan, Supriya, et al. “Tobacco Carcinogen-Induced Production of GM-CSF Activates CREB to Promote Pancreatic Cancer.Cancer Res, vol. 78, no. 21, Nov. 2018, pp. 6146–58. Pubmed, doi:10.1158/0008-5472.CAN-18-0579.
URI
https://scholars.duke.edu/individual/pub1429385
PMID
30232221
Source
pubmed
Published In
Cancer Res
Volume
78
Published Date
Start Page
6146
End Page
6158
DOI
10.1158/0008-5472.CAN-18-0579

Could the PD-1 Pathway Be a Potential Target for Treating Small Intestinal Adenocarcinoma?

Objectives: The programmed death 1 (PD-1) pathway is upregulated in the immune microenvironment of many cancers. In this study, we examined the PD-1 pathway and the immune microenvironment of small intestinal adenocarcinomas by immunohistochemistry. Methods: From our department pathology archives we identified 42 small intestinal adenocarcinomas from between 2000 and 2015, with blocks available for IHC studies. Tumors were immunohistochemically stained for CD3, CD4, CD8, CD20, PD-1, and programmed death ligand 1 (PD-L1) expression. Results: PD-1 was expressed by intratumoral and peritumoral lymphocytes in 35 of 42 (83%) cases. PD-L1 expression on tumor cells and immune cells was observed in seven of 42 (17%), and 18 of 42 (43%) cases, respectively. PD-L1 was mainly expressed by histiocytes capping cancerous glands/nests at the invasive front or by most tumor cells in medullary carcinomas. All the PD-L1+ tumors also expressed PD-1. The tumors expressing PD-L1 contained more CD3+, CD4+, and CD8+ T cells, but showed a lower CD4+/CD8+ ratio than those without expression of PD-L1. Conclusions: PD-1 and PD-L1 are highly expressed by most small intestinal adenocarcinomas. Blockage of the PD-1 pathway should be evaluated in the treatment of small intestinal adenocarcinomas.
Authors
Thota, R; Gonzalez, RS; Berlin, J; Cardin, DB; Shi, C
MLA Citation
Thota, Ramya, et al. “Could the PD-1 Pathway Be a Potential Target for Treating Small Intestinal Adenocarcinoma?Am J Clin Pathol, vol. 148, no. 3, Sept. 2017, pp. 208–14. Pubmed, doi:10.1093/AJCP/AQX070.
URI
https://scholars.duke.edu/individual/pub1429411
PMID
28821192
Source
pubmed
Published In
Am J Clin Pathol
Volume
148
Published Date
Start Page
208
End Page
214
DOI
10.1093/AJCP/AQX070

MEK Resistance via Amphiregulin Mediated EGFR-STAT3 Activation in Pancreatic Cancer

Authors
Lamichhane, P; Nagathihalli, NS; Castellanos, J; Shi, C; Roberts, C; Vansaun, M; Merchant, N
MLA Citation
Lamichhane, P., et al. “MEK Resistance via Amphiregulin Mediated EGFR-STAT3 Activation in Pancreatic Cancer.” Pancreas, vol. 45, no. 10, LIPPINCOTT WILLIAMS & WILKINS, 2016, pp. 1518–1518.
URI
https://scholars.duke.edu/individual/pub1429572
Source
wos
Published In
Pancreas
Volume
45
Published Date
Start Page
1518
End Page
1518