Shiao-Wen David Hsu

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

William Dalton Family Assistant Professor of Medical Oncology, in the School of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2001

University of North Carolina - Chapel Hill

Medical Resident, Medicine

University of Texas at Dallas

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

Identifying gene-environment interactions that confer metabolic vulnerabilities in cancer

Administered By
Pharmacology & Cancer Biology
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Targeting KRAS (G12C) Mutant in Colorectal Cancer

Administered By
Medicine, Medical Oncology
Awarded By
Amgen, Inc.
Role
Principal Investigator
Start Date
End Date

Determining the Efficacy of Liposomal Gemcitabine in Patient Derived Xenografts (PDXs)

Administered By
Medicine, Medical Oncology
Awarded By
FUJIFILM Pharmaceuticals U.S.A.
Role
Principal Investigator
Start Date
End Date

Targeting the TK1 receptor in colorectal and lung PDX using CarT cell and Motorcar cell

Administered By
Medicine, Medical Oncology
Awarded By
Thunder Biotech
Role
Principal Investigator
Start Date
End Date

Targeting Calreticulin in Colorectal Cancer Liver Metastasis

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

In Vivo Selection Against Human Colorectal Cancer Xenografts Identifies an Aptamer That Targets RNA Helicase Protein DHX9.

The ability to selectively target disease-related tissues with molecules is critical to the design of effective therapeutic and diagnostic reagents. Recognizing the differences between the in vivo environment and in vitro conditions, we employed an in vivo selection strategy to identify RNA aptamers (targeting motifs) that could localize to tumor in situ. One of the selected molecules is an aptamer that binds to the protein DHX9, an RNA helicase that is known to be upregulated in colorectal cancer. Upon systemic administration, the aptamer preferentially localized to the nucleus of cancer cells in vivo and thus has the potential to be used for targeted delivery.
Authors
Mi, J; Ray, P; Liu, J; Kuan, C-T; Xu, J; Hsu, D; Sullenger, BA; White, RR; Clary, BM
MLA Citation
Mi, Jing, et al. “In Vivo Selection Against Human Colorectal Cancer Xenografts Identifies an Aptamer That Targets RNA Helicase Protein DHX9.Mol Ther Nucleic Acids, vol. 5, Apr. 2016, p. e315. Pubmed, doi:10.1038/mtna.2016.27.
URI
https://scholars.duke.edu/individual/pub1131134
PMID
27115840
Source
pubmed
Published In
Molecular Therapy. Nucleic Acids
Volume
5
Published Date
Start Page
e315
DOI
10.1038/mtna.2016.27

Retraction: Acharya CR, et al. Gene expression signatures, clinicopathological features, and individualized therapy in breast cancer. JAMA. 2008;299(13):1574-1587.

Authors
Acharya, CR; Hsu, DS; Anders, CK; Anguiano, A; Salter, KH; Walters, KS; Redman, RC; Tuchman, SA; Moylan, CA; Mukherjee, S; Barry, WT; Dressman, HK; Ginsburg, GS; Marcom, KP; Garman, KS; Lyman, GH; Nevins, JR; Potti, A
MLA Citation
Acharya, Chaitanya R., et al. “Retraction: Acharya CR, et al. Gene expression signatures, clinicopathological features, and individualized therapy in breast cancer. JAMA. 2008;299(13):1574-1587.Jama, vol. 307, no. 5, Feb. 2012, p. 453. Pubmed, doi:10.1001/jama.2012.2.
URI
https://scholars.duke.edu/individual/pub739348
PMID
22228686
Source
pubmed
Published In
Jama
Volume
307
Published Date
Start Page
453
DOI
10.1001/jama.2012.2

A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities.

Gene expression profiles provide an opportunity to dissect the heterogeneity of solid tumors, including colon cancer, to improve prognosis and predict response to therapies. Bayesian binary regression methods were used to generate a signature of disease recurrence in patients with resected early stage colon cancer validated in an independent cohort. A 50-gene signature was developed that effectively distinguished early stage colon cancer patients with a low or high risk of disease recurrence. RT-PCR analysis of the 50-gene signature validated 9 of the top 10 differentially expressed genes. When applied to two independent validation cohorts of 55 and 73 patients, the 50-gene model accurately predicted recurrence. Standard Kaplan-Meier survival analysis confirmed the prognostic accuracy (P < 0.01, log rank), as did multivariate Cox proportional hazard models. We tested potential targeted therapeutic options for patients at high risk for disease recurrence and found a clinically important relationship between sensitivity to celecoxib, LY-294002 (PI3kinase inhibitor), retinol, and sulindac in colon cancer cell lines expressing the poor prognostic phenotype (P < 0.01, t test), which performed better than standard chemotherapy (5-FU and oxaliplatin). We present a genomic strategy in early stage colon cancer to identify patients at highest risk of recurrence. An ability to move beyond current staging by refining the estimation of prognosis in early stage colon cancer also has implications for individualized therapy.
Authors
Garman, KS; Acharya, CR; Edelman, E; Grade, M; Gaedcke, J; Sud, S; Barry, W; Diehl, AM; Provenzale, D; Ginsburg, GS; Ghadimi, BM; Ried, T; Nevins, JR; Mukherjee, S; Hsu, D; Potti, A
MLA Citation
Garman, Katherine S., et al. “A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities.Proc Natl Acad Sci U S A, vol. 105, no. 49, Dec. 2008, pp. 19432–37. Pubmed, doi:10.1073/pnas.0806674105.
URI
https://scholars.duke.edu/individual/pub768510
PMID
19050079
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Volume
105
Published Date
Start Page
19432
End Page
19437
DOI
10.1073/pnas.0806674105

Cystine Deprivation Triggers Programmed Necrosis in VHL-Deficient Renal Cell Carcinomas.

Oncogenic transformation may reprogram tumor metabolism and render cancer cells addicted to extracellular nutrients. Deprivation of these nutrients may therefore represent a therapeutic opportunity, but predicting which nutrients cancer cells become addicted remains difficult. Here, we performed a nutrigenetic screen to determine the phenotypes of isogenic pairs of clear cell renal cancer cells (ccRCC), with or without VHL, upon the deprivation of individual amino acids. We found that cystine deprivation triggered rapid programmed necrosis in VHL-deficient cell lines and primary ccRCC tumor cells, but not in VHL-restored counterparts. Blocking cystine uptake significantly delayed xenograft growth of ccRCC. Importantly, cystine deprivation triggered similar metabolic changes regardless of VHL status, suggesting that metabolic responses alone are not sufficient to explain the observed distinct fates of VHL-deficient and restored cells. Instead, we found that increased levels of TNFα associated with VHL loss forced VHL-deficient cells to rely on intact RIPK1 to inhibit apoptosis. However, the preexisting elevation in TNFα expression rendered VHL-deficient cells susceptible to necrosis triggered by cystine deprivation. We further determined that reciprocal amplification of the Src-p38 (MAPK14)-Noxa (PMAIP1) signaling and TNFα-RIP1/3 (RIPK1/RIPK3)-MLKL necrosis pathways potentiated cystine-deprived necrosis. Together, our findings reveal that cystine deprivation in VHL-deficient RCCs presents an attractive therapeutic opportunity that may bypass the apoptosis-evading mechanisms characteristic of drug-resistant tumor cells. Cancer Res; 76(7); 1892-903. ©2016 AACR.
Authors
Tang, X; Wu, J; Ding, C-K; Lu, M; Keenan, MM; Lin, C-C; Lin, C-A; Wang, CC; George, D; Hsu, DS; Chi, J-T
MLA Citation
Tang, Xiaohu, et al. “Cystine Deprivation Triggers Programmed Necrosis in VHL-Deficient Renal Cell Carcinomas.Cancer Res, vol. 76, no. 7, Apr. 2016, pp. 1892–903. Pubmed, doi:10.1158/0008-5472.CAN-15-2328.
URI
https://scholars.duke.edu/individual/pub1165749
PMID
26833124
Source
pubmed
Published In
Cancer Res
Volume
76
Published Date
Start Page
1892
End Page
1903
DOI
10.1158/0008-5472.CAN-15-2328

Histological and molecular evaluation of patient-derived colorectal cancer explants.

Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs) by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.
Authors
MLA Citation
Uronis, Joshua M., et al. “Histological and molecular evaluation of patient-derived colorectal cancer explants.Plos One, vol. 7, no. 6, 2012, p. e38422. Pubmed, doi:10.1371/journal.pone.0038422.
URI
https://scholars.duke.edu/individual/pub747887
PMID
22675560
Source
pubmed
Published In
Plos One
Volume
7
Published Date
Start Page
e38422
DOI
10.1371/journal.pone.0038422