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:

The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells.

In this study, we define the genetic landscape of mantle cell lymphoma (MCL) through exome sequencing of 56 cases of MCL. We identified recurrent mutations in ATM, CCND1, MLL2, and TP53. We further identified a number of novel genes recurrently mutated in patients with MCL including RB1, WHSC1, POT1, and SMARCA4. We noted that MCLs have a distinct mutational profile compared with lymphomas from other B-cell stages. The ENCODE project has defined the chromatin structure of many cell types. However, a similar characterization of primary human mature B cells has been lacking. We defined, for the first time, the chromatin structure of primary human naïve, germinal center, and memory B cells through chromatin immunoprecipitation and sequencing for H3K4me1, H3K4me3, H3Ac, H3K36me3, H3K27me3, and PolII. We found that somatic mutations that occur more frequently in either MCLs or Burkitt lymphomas were associated with open chromatin in their respective B cells of origin, naïve B cells, and germinal center B cells. Our work thus elucidates the landscape of gene-coding mutations in MCL and the critical interplay between epigenetic alterations associated with B-cell differentiation and the acquisition of somatic mutations in cancer.
Authors
Zhang, J; Jima, D; Moffitt, AB; Liu, Q; Czader, M; Hsi, ED; Fedoriw, Y; Dunphy, CH; Richards, KL; Gill, JI; Sun, Z; Love, C; Scotland, P; Lock, E; Levy, S; Hsu, DS; Dunson, D; Dave, SS
MLA Citation
Zhang, Jenny, et al. “The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells.Blood, vol. 123, no. 19, May 2014, pp. 2988–96. Pubmed, doi:10.1182/blood-2013-07-517177.
URI
https://scholars.duke.edu/individual/pub1025975
PMID
24682267
Source
pubmed
Published In
Blood
Volume
123
Published Date
Start Page
2988
End Page
2996
DOI
10.1182/blood-2013-07-517177

A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer.

PURPOSE: For patients with metastatic colorectal cancer (mCRC), no standard therapy exists after progression on 5-fluorouracil, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab. Preclinical data demonstrated that combined vascular endothelial growth factor and mammalian target of rapamycin inhibition has greater antiangiogenic and antitumor activity than either monotherapy. A phase I study of bevacizumab plus everolimus demonstrated that the combination is safe; activity was seen in several patients with refractory mCRC. METHODS: Fifty patients with refractory mCRC were enrolled and received bevacizumab at 10 mg/kg every 2 weeks and everolimus at 10 mg orally daily. RESULTS: Of the 50 patients enrolled, the median age was 56 years and the median number of prior regimens was four. Forty-seven patients (96%) had prior bevacizumab exposure and 42 patients (84%) had documented progression on prior bevacizumab-based therapy. Forty-nine patients were evaluable for response; eight patients had minor responses (16%) and an additional 15 patients (30%) had stable disease (SD). No complete or partial responses were seen. The median progression-free survival interval was 2.3 months; however, 26% of patients achieved prolonged SD for ≥6 months, and three patients (6%) were on study for >1 year. The median overall survival duration was 8.1 months. The most common grade 1-2 toxicities were mucositis (68%) and hyperlipidemia (64%). Clinically significant grade ≥3 toxicities included hypertension (14%), fistula/abscess/perforation (8%), mucositis (6%), and hemorrhage (2%). CONCLUSIONS: Bevacizumab plus everolimus is generally tolerable but may have risks related to mucosal damage and/or wound healing. Bevacizumab plus everolimus appears to have modest activity in refractory mCRC in patients.
Authors
Altomare, I; Bendell, JC; Bullock, KE; Uronis, HE; Morse, MA; Hsu, SD; Zafar, SY; Blobe, GC; Pang, H; Honeycutt, W; Sutton, L; Hurwitz, HI
MLA Citation
Altomare, Ivy, et al. “A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer.Oncologist, vol. 16, no. 8, 2011, pp. 1131–37. Pubmed, doi:10.1634/theoncologist.2011-0078.
URI
https://scholars.duke.edu/individual/pub743278
PMID
21795432
Source
pubmed
Published In
Oncologist
Volume
16
Published Date
Start Page
1131
End Page
1137
DOI
10.1634/theoncologist.2011-0078

Role of mouse cryptochrome blue-light photoreceptor in circadian photoresponses.

Cryptochromes are photoactive pigments in the eye that have been proposed to function as circadian photopigments. Mice lacking the cryptochrome 2 blue-light photoreceptor gene (mCry2) were tested for circadian clock-related functions. The mutant mice had a lower sensitivity to acute light induction of mPer1 in the suprachiasmatic nucleus (SCN) but exhibited normal circadian oscillations of mPer1 and mCry1 messenger RNA in the SCN. Behaviorally, the mutants had an intrinsic circadian period about 1 hour longer than normal and exhibited high-amplitude phase shifts in response to light pulses administered at circadian time 17. These data are consistent with the hypothesis that CRY2 protein modulates circadian responses in mice and suggest that cryptochromes have a role in circadian photoreception in mammals.
Authors
Thresher, RJ; Vitaterna, MH; Miyamoto, Y; Kazantsev, A; Hsu, DS; Petit, C; Selby, CP; Dawut, L; Smithies, O; Takahashi, JS; Sancar, A
MLA Citation
Thresher, R. J., et al. “Role of mouse cryptochrome blue-light photoreceptor in circadian photoresponses.Science, vol. 282, no. 5393, Nov. 1998, pp. 1490–94. Pubmed, doi:10.1126/science.282.5393.1490.
URI
https://scholars.duke.edu/individual/pub777458
PMID
9822380
Source
pubmed
Published In
Science (New York, N.Y.)
Volume
282
Published Date
Start Page
1490
End Page
1494
DOI
10.1126/science.282.5393.1490

Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.

PURPOSE: Dasatinib inhibits src family kinases and has anti-angiogenic properties. We conducted a phase I study of dasatinib, capecitabine, oxaliplatin, and bevacizumab (CapeOx/bevacizumab), with an expansion cohort in metastatic colorectal cancer (CRC). METHODS: Patients were enrolled in a dose escalation cohort to establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Using a "3 + 3" design, twelve patients with advanced solid tumors received dasatinib (50 mg twice daily or 70 mg daily), capecitabine (850 mg/m(2) twice daily, days 1-14), oxaliplatin (130 mg/m(2) on day 1) and bevacizumab (7.5 mg/kg on day1), every 3 weeks. Ten patients with previously untreated metastatic CRC were then enrolled in an expansion cohort. Activated src (src(act)) expression was measured by immunohistochemistry, using an antibody that selectively recognizes the active conformation of src (clone 28). RESULTS: Twenty-two patients were enrolled between June 2009 and May 2011. Two DLTs were observed in the 50 mg bid dasatinib cohort, and one DLT was observed in the 70 mg daily dasatinib cohort. The MTD and RP2D for dasatinib was 70 mg daily. The most common treatment-related adverse events were fatigue (20; 91 %) and diarrhea (18; 82 %). Biomarker analysis of src(act) expression demonstrated that the overall response rate (ORR) was 75 % (6/8) for patients with high src(act) expression (IHC ≥ 2), compared to 0 % (0/8) for patients with low srcact expression (IHC 0 or 1); (p = 0.007). CONCLUSIONS: The RP2D of dasatinib is 70 mg daily in combination with CapeOx/bevacizumab. High levels of srcact expression may predict those patients most likely to benefit from dasatinib.
Authors
Strickler, JH; McCall, S; Nixon, AB; Brady, JC; Pang, H; Rushing, C; Cohn, A; Starodub, A; Arrowood, C; Haley, S; Meadows, KL; Morse, MA; Uronis, HE; Blobe, GC; Hsu, SD; Zafar, SY; Hurwitz, HI
MLA Citation
Strickler, John H., et al. “Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.Invest New Drugs, vol. 32, no. 2, Apr. 2014, pp. 330–39. Pubmed, doi:10.1007/s10637-013-0042-9.
URI
https://scholars.duke.edu/individual/pub967259
PMID
24173967
Source
pubmed
Published In
Invest New Drugs
Volume
32
Published Date
Start Page
330
End Page
339
DOI
10.1007/s10637-013-0042-9

Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer (Proceedings of the National Academy of Sciences of the United States of America (2009) 106, 13 (5312-5317) DOI: 10.1073/pnas.0900827106)

Authors
Hsu, DS; Acharya, CR; Balakumaran, BS; Riedel, RF; Kim, MK; Stevenson, M; Tuchman, S; Mukherjee, S; Barry, W; Dressman, HK; al, E
MLA Citation
Hsu, D. S., et al. “Characterizing the developmental pathways TTF-1, NKX2-8, and PAX9 in lung cancer (Proceedings of the National Academy of Sciences of the United States of America (2009) 106, 13 (5312-5317) DOI: 10.1073/pnas.0900827106).” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 35, 2011, pp. 14705-. Scival, doi:10.1073/pnas.1111196108.
URI
https://scholars.duke.edu/individual/pub769520
Source
scival
Published In
Proceedings of the National Academy of Sciences of the United States of America
Volume
108
Published Date
Start Page
14705-
DOI
10.1073/pnas.1111196108