About Dr. Zhang
Dr. Weiguo "Wayne" Zhang has more than 15 years research experience in a field of acute myeloid leukemia (AML) therapy at the The University of Texas MD Anderson Cancer Center in the Department of Leukemia, closely working with Dr. Michael Andreeff, a leading scientist in a leukemia research field. The overall objectives of his research entail understanding signaling regulation of leukemogenesis and development of novel and effective therapeutic regimens for curing leukemia. In particular, his research interests include: 1) identifying novel small molecule tyrosine kinase inhibitors for targeting AML with the fms-like tyrosine kinase 3 ( FLT3 ) mutations; 2) investigating mechanisms of relapse/resistance of AML patients who received FLT3-inhibition therapy or conventional chemotherapy; and 3) developing novel combinatorial regimens for overcoming resistance to FLT3-targeted therapy.
Dr. Zhang’s most important contribution is discovery of sorafenib as an active targeting drug against FLT3 mutant leukemias, which has been used worldwide currently. He also developed several combinatorial regimens based on FLT3-targeted therapy. He was first to show the importance of the “vascular niche” in AML by inhibiting E-selectin and achieving significantly longer survival in AML models. Recently, he investigated a novel agent with femtomolar activity in AML, both FLT3-mutated and un-mutated, which demonstrated encouraging results for overcoming FLT3-inhibitor resistance.
Dr. Zhang’s ultimate goal is to develop novel concepts or optimized combinatorial strategies for overcoming resistance of anti-tyrosine kinase-targeted therapy and helping for curing myeloid leukemias.
Assistant Professor, Department of Leukemia - Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
|1998||Shanghai Second Medical University (SSMU), Shanghai, CHN, PHD, Oral Medicine|
|1988||Shanghai Second Medical University (SSMU), Shanghai, CHN, MSc, Pathology|
|1983||Shanghai Second Medical University (SSMU), Shanghai, CHN, MD, Oral Medicine|
|2000-2002||Research Fellowship, Baylor College of Medicine, Department of Molecular and Cell Biology, Houston, TX|
|1999-2000||Research Fellowship, Department of Laboratory and Pathology Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX|
|1998-1999||Research Fellowship, Department of Pediatric Dentistry, School of Dentistry, The University of Texas Health Science Center at San Antonio, San Antonio, TX|
|1988-1991||Research Residency, Department of Pathology, Shanghai Ninth People's Hospital, Shanghai Second Medical University, Shanghai|
|1983-1985||Research Residency, Department of Stomatology, Shanghai East-China Hospital, Shanghai|
Instructor, Department of Stem Cell Transplantation - Research, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 2003 - 2010
Associate Professor, Department of Pathology, School of Stomatology, Shanghai Second Medical University (SSMU), Shanghai, 1995 - 1998
Lecturer, Department of Pathology, School of Stomatology, Shanghai Second Medical University (SSMU), Shanghai, 1991 - 1994
Director, Department of Pathology, Shanghai Ninth People's Hospital, Shanghai Second Medical University, Shanghai, 1996 - 1998
|1996||Science & Technology Achievement Award (Grade III, No. 96303902, Second Contributor), Ministry of Public Health, China|
|1992||Science & Technology Progress Award (Grade III, No. 923197, Second Contributor), Shanghai Municipality, China|
|1992||Nature Science Award (Grade III, No. 92Z-3-015-04, Fourth Contributor), Chinese Academy of Sciences|
|1992||Science & Technology Progress Award (Grade II, No. 912086, Seventh Contributor), Shanghai Municipality China|
- Zhang W, Ly C, Ishizawa J, Mu H, Ruvolo V, Shacham S, Daver N, Andreeff M. Combinatorial targeting of XPO1 and FLT3 exerts synergistic anti-leukemia effects through induction of differentiation and apoptosis in FLT3-mutated acute myeloid leukemias: from concept to clinical trial. Haematologica 103(10):1642-1653, 2018. e-Pub 2018. PMID: 29773601.
- Jiang X, Mak PY, Mu H, Tao W, Mak DH, Kornblau S, Zhang Q, Ruvolo P, Burks JK, Zhang W, McQueen T, Pan R, Zhou H, Konopleva M, Cortes J, Liu Q, Andreeff M, Carter BZ. Disruption of Wnt/β-Catenin Exerts Antileukemia Activity and Synergizes with FLT3 Inhibition inFLT3-Mutant Acute Myeloid Leukemia. Clin Cancer Res 24(10):2417-2429, 2018. e-Pub 2018. PMID: 29463558.
- Zhang W, Borthakur G, Gao C, Chen Y, Mu H, Ruvolo VR, Nomoto K, Zhao N, Konopleva M, Andreeff M. The dual MEK/FLT3 inhibitor E6201 exerts cytotoxic activity against acute myeloid leukemia cells harboring resistance-conferring FLT3 mutations. Cancer Res 76(6):1528-37, 2016. e-Pub 2016. PMID: 26822154.
- Zhang W, Ruvolo VR, Gao C, Zhou L, Bornmann W, Tsao T, Schober WD, Smith P, Guichard S, Konopleva M, Andreeff M. Evaluation of Apoptosis Induction by Concomitant Inhibition of MEK, mTOR, and Bcl-2 in Human Acute Myeloid Leukemia Cells. Mol Cancer Ther 13(7):1848-59, 2014. e-Pub 2014. PMID: 24739393.
- Ling X, Spaeth E, Chen Y, Shi Y,Zhang W, Schober W, Hail N, Konopleva M, Andreeff M. The CXCR4 antagonist AMD3465 regulates oncogenic signaling and invasiveness in vitro and prevents breast cancer growth and metastasis in vivo. PLoS One 8(3):e58426, 2013. e-Pub 2013. PMID: 23484027.
- Zhang W, Konopleva M, Burks JK, Dywer KC, Schober WD, Yang JY, McQueen TJ, Hung MC, Andreeff M. Blockade of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase and Murine Double Minute Synergistically Induces Apoptosis in Acute Myeloid Leukemia via BH3-Only Proteins Puma and Bim. Cancer Res 70(6):2424-34, 2010. e-Pub 2010. PMID: 20215498.
- Xiaoyang L, Marini F, Konopleva M, Schober WD, Shi Y-X, Burks JK, Dwyer KC,Zhang W, Yuan X, Lu H, Caldwell L, Andreeff M. Mesenchymal stem cells overexpressing IFN-beta inhibit breast cancer growth and metastases through Stat3 signaling in a syngeneic tumor model. Journal of Cancer Microenvironment:83-95, 2010.
- Mori S, Cortes J, Kantarjian H,Zhang W, Andreef M, Ravandi F. Potential role of sorafenib in the treatment of acute myeloid leukemia. Leuk Lymphoma 49(12):2246-55, 2008. PMID: 19052971.
- Zhang W, Konopleva M, Shi Y, Ling X, Andreeff M. Combination of Sorafenib and Arsenic Trioxide Exerts Synergistic Anti-Leukemia Effects in Sorafenib-resisatnt FTL3-ITD-harboring AML Cells. Blood 112, 2008. e-Pub 2008.
- Zhang W, Konopleva M, Shi YX, McQueen T, Harris D, Ling X, Estrov Z, Quintás-Cardama A, Small D, Cortes J, Andreeff M. Mutant FLT3: A direct target of sorafenib in acute myelogenous leukemia. J Natl Cancer Inst 100(3):184-198, 2008. e-Pub 2008. PMID: 18230792.
- Zeng Z, Samudio IJ,Zhang W, Estrov Z, Pelicano H, Harris D, Frolova O, Hail N, Jr, Chen W, Kornblau SM, Huang P, Lu Y, Mills GB, Andreeff M, Konopleva M. Simultaneous inhibition of PDK1/AKT and Fms-like tyrosine kinase 3 signaling by a small-molecule KP372-1 induces mitochondrial dysfunction and apoptosis in acute myelogenous leukemia. Cancer Res 66:3737-46, 2006. PMID: 16585200.
- Konopleva M,Zhang W, Shi YX, McQueen T, Tsao T, Abdelrahim M, Munsell MF, Johansen M, Yu D, Madden T, Safe SH, Hung MC, Andreeff M. Synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest in HER2-overexpressing breast cancer cells. Mol Cancer Ther 5:317-28, 2006. PMID: 16505105.
- Zhang W, McQueen T, Schober W, Rassidakis G, Andreeff M, Konopleva M. Leukotriene B4 receptor inhibitor LY293111 induces cell cycle arrest and apoptosis in human anaplastic large-cell lymphoma cells via JNK phosphorylation. Leukemia 19:1977-84, 2005. PMID: 16151469.
- Zhang W, Shi HY, Zhang M. Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteins. BMC Cancer 5:50, 2005. e-Pub 2005. PMID: 15907209.
- Latha K, Zhang W, Cella N, Shi HY, Zhang M. Maspin mediates increased tumor cell apoptosis upon induction of the mitochondrial permeability transition. Mol Cell Biol 25:1737-48, 2005.
- Abraham S, Zhang W, Greenberg N, et al. Maspin functions as tumor suppressor by increasing cell adhesion to extracellular matrix in prostate tumor cells. J Urol 169:1157-61, 2003.
- Ohtake S, Cheng J, Ida H, Suzuki M, Ohshiro K, Zhang W, Saku T. Precancerous foci in pleomorphic adenoma of the salivary gland: recognition of focal carcinoma and atypical tumor cells by P53 immunohistochemistry. J Oral Pathol Med 31:590-7, 2002. PMID: 12406304.
- Zhang W, Zhang M. Tissue microarray analysis of maspin expression and its reverse correlation with mutant p53 in various cancers. Int J Oncol 20:1145-50, 2002.
- Shi HY, Zhang W, Liang R, Abraham S, Kittrell FS, Medina D, Zhang M. Blocking tumor growth, invasion and metastasis by maspin in a syngeneic breast cancer model. Cancer Research 61:6945, 2001.
- Zhang ZY, Wu YQ, Zhang W, Tian Z, Cao J. The expression of E-cadherin-catenin complex in adenoid cystic carcinoma of salivary glands. Chin J Dent Res 3(3):36-9, 2000. PMID: 11314533.
- Wang Q, Zhang W. The expression of oncoprotein p53 and C-erbB-2 on squamous cell carcinomas of oral mucosa and the epithelium adjacent to the tumors. Shanghai J Stomatol 9:191, 2000.
- Zhu P, Zhang W. The role of matrix vesicles during development of the mineralizing tissues of tooth germ and craniofacial bone. Chung Hua Kou Chiang Hsueh Tsa Chih 35:69, 2000.
- Yan Y, Liu Z, Zhang W. In vitro study of the effects of endothelin-1 on human dental pulp cells. Chin J Dent Res 2(2):5, 1999. PMID: 10863400.
- Zhang L, Zhang W. Telomerase hTR and hTRT gene expression in oral precancerous lesions and squamous cell carcinomas. Chin J Dent Res 2(2):43, 1999. PMID: 10863406.
- Wu YQ, Zhang W. The expression of adhesion molecules in human salivary adenoid cystic carcinomas cell line. Shanghai J Stomatol 8:166, 1999.
- Wu YQ, Wang Y, Zhang W. The expression of CD44s and CD44v6 in human salivary adenoid cystic carcinomas. Shanghai J Stomatol 8:159, 1999.
- Wu YQ, Zhang W. The expression of E-cadherin-catenin complex in human salivary adenoid cystic carcinomas. Shanghai J Stomatol 8:163, 1999.
- Zhang L, Zhang W, Liu Z. Research on expression of telomerase hTR gene in oral precancerous lesion and squamous cell carcinoma. Shanghai J Stomatol 8:70, 1999.
- Zhang L, Zhang W, Liu Z. Telomerase hTRT mRNA expression in oral squamous cell carcinomas. West China J Stomatol 17(4):307, 1999.
- Li J, Zhang W. Clinicopathological analysis of 15 cases of desmoplastic ameloblastoma. West China J Stomatol 6:138, 1998.
- Zhang W, Wang L, Liu Z. The effect of fluoride on bone extracellular matrix proteins expression in rat calvarial osteoblast in culture. Shanghai J Stomatol 7:94, 1998.
- Zhang W, Liu Z. The effects of fluoride and dexamethasone on the phenotypic development of osteoblast growing on the demineralized dental root surface. Shanghai J Stomatol 7:99, 1998.
- Zhang W, Wang Y, Wang L, et al. Expression of non-collagenous proteins during development of craniofacial mineralized tissues of rats. Chin J Oral Maxillofacial Surg 8:190, 1998.
- Zhang W, Wang L, Liu Z. The influence of fluoride on the development of the osteoblast phenotype in rat calvarial osteoblasts: an in vitro study. Shanghai J Stomatol 7:88, 1998.
- Chen J, Aufdemorte TB, Jiang H, Liu AR, Zhang W, Thomas HF. Neoplastic odontogenic epithelial cells express bone sialoprotein. Histochem J 30(1):1, 1998. PMID: 9539200.
- Zhang W, Konopleva M, Ruvolo V, McQueen T, Evans R, Bornmann W, McCubrey J, Cortes J. Sorafenib induces apopotosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway. Leukemia 22:808-18. e-Pub 2008. PMID: 18200035.
- Zhang W, Gao C, Konopleva M, Chen Y, Jacamo RO, Borthakur G, Cortes JE, Ravandi F, Ramachandran A, Andreeff M. Reversal of Acquired Drug Resistance in FLT3-Mutated Acute Myeloid Leukemia Cells via Distinct Drug Combination Strategies. Clin Cancer Res. e-Pub 2014. PMID: 24619500.
- Borthakur G, Kantarjian H, Ravandi F,Zhang W, Konopleva M, Wright JJ, Faderl S, Verstovsek S, Mathews S, Andreeff M, Cortes JE. Phase 1 Study of sorafenib in patients with refractory or relapsed acute leukemias. Haematologica 96(1):62-8. e-Pub 2010. PMID: 20952518.
- Mori S, Cortes J, Kantarjian H, Zhang W, Andreeff M, Ravandi F Potential role of sorafenib in the treatment of acute myeloid lekemia. Review. Leukemia and Lymphoma 49:2246-2255, 2008.
- Zhang W Modeling human breast cancer metastasis in mice: maspin as a paradigm. Review. Histo Histopathol 18:201-6, 2003.
- Bao X, Zhang W The mechanisms of multiple drug resistance and reversion in head and neck tumors. Review. Chinese J New Drugs Clin Rem 19:492, 2000.
- Zhang L, Zhang W Telomere in cell aging and tumorogenesis. Review. Chinese J Oral Maxillofacial Surg 9:54, 1999.
- Zhang W The phenotype differentiation and gene regulation of osteoblasts. Review. Shanghai J Stomatol 7:179, 1998.
- Wu YQ, Zhang W, Zhang Z Tumor metastases and adhesion molecules. Review. World Med 25:176, 1998.
- Andreeff, M.,Zhang W , Kumar, P., Zernovak, O., Daver, N., Isoyama, T., Iwanaga, K., Togashi, N., Seki. T.. Synergistic anti-leukemic activity with combination of FLT3 inhibitor quizartinib and MDM2 inhibitor milademetan in FLT3-ITD mutant/p53 wild-type acute myeloid leukemia models. ASH Annual Meeting, 2018.
- Daver, N., Assi, R., Kantarjian, H., Cortes, J., Ravandi, F., Konopleva, M., Kadia, T., Borthakur, G., Jabbour, E., DiNardo1, CD., Ning, J., Nogueras-Gonzalez, G., Pierce, S., Kelly, M., Gombos, D., Kornblau, S., Zhang W, Andreeff. M.. Final Results of Phase I/II study of Selinexor (SEL) with Sorafenib in Patients (pts) with Relapsed and/or Refractory (R/R) FLT3 mutated Acute Myeloid Leukemia (AML). ASH Annual Meeting, 2018.
- Ruvolo, PP., Ma, H., Ruvolo, VR., Zhang, X. Mu, H., Yasuhiro, T., Tanaka, K., Yoshizawa, T., Zhang W, Cortes, J., Andreeff, M., Post, SM.. TAM inhibitor ONO-7475 combination with Sorafenib is effective using in vitro and in vivo models of FLT3 ITD Acute Myeloid Leukemia. ASH Annual Meeting, 2018.
- Zhang W, Yu, G., Zhang, H., Ly, C., Yuan, B., Ruvolo, V., Piya, S., Bhattacharya, S., Zhang, Q., Borthakur, G., Battula, VL., Konopleva, M., Rice, WG., Andreeff, M.. Concomitant targeting of FLT3 and BTK with CG’806 overcomes FLT3-inhibitor resistance through inhibition of autophagy. ASH Annual Meeting, 2018.
- Ly C, Zhang W, Ruvolo V, Shah N, Andreeff M.. Mechanism-based combinatorial strategy for overcoming FLT3-inhibitor resistance in dual FLT3 ITD and TKD point mutations. ASH Annual Meeting, 2016.
- Zhang W, Konopleva M,Tsao T,Schober W,Andreeff M.. Simultaneous blockade of MEK and mTOR kinase signaling synergizes pro-apoptotic effects in AML cells, which is further potential by interfering with dimerization of BH3 domains. AACR 101st annual meeting, 2010.
- Zhang W, Konopleva M, Burks JK, Dwyer KC, Schober WD, Yang J-Y, McQueen T, Andreeff M. Apoptosis Induction In Acute Myeloid Leukemia by Inhibition of MEK and MDM2 is Strongly Associated With the BH3 Only Proteins Puma and Bim. E J Can 6, 2008.
- Ravandi F, Cortes J, Garcia-Manero G, O'Brien S, Borthakur G, Pierce S, Brandt M, Lang M, Zhang W, Luthra R, Jones D, Levis M, Konopleva M, Andreeff M, Katarjian H. Combination of sorafenib, idarubicin, and cytarabine has a high response rate in patients with newly diagnosed acute myeloid leukemia younger than 65 years. Blood 112:768, 2008.
- Zhang W, Konopleva M, Shi Y, Ling X, Andreeff M. Combination of sorafenib and arsenic trioxide exerts synergistic anti-leukemia effects in sorafenib-resistant FLT3-ITD-harboring AML cells. Blood 112:2656, 2008.
- Zhang W, Konopleva M, Schober WD, McQueen T, Andreeff M. MEK inhibitor AZD6244 induces cell growth arrest and synergizes with Nutlin-3a-mediated cell death by upregulating p53 and PUMA levels in AML. Blood 110(11):201a, 2007.
- Quintas-Cardama A, Kantarjian H, Andreeff M, Faderi S, Wright J, Zhang W, Konopleva M, Verstovsek S, Borthakur G, Cortes J. Phase I trial of intermittent administration of sorafenib (Bay 43-9006) for patients with refractory/relapsed acute myelogenous leukemia. J Clin Oncol 25(18S):7018, 2007.
- Zhang W, Konopleva M, Shi Y-X, Harris D, Small D, Ling X, Estrov Z, Cortes J, Andreeff M. Sorafenib (BAY 43-9006) directly targets FLT3-ITD in acute myelogenous leukemia. Blood 108(11):255, 2006.
- Andreeff M, Konopleva M, Watt JC, Samudio IJ, Satterthwait AC, Kitada S, Zhang W, Reed JC. A novel peptide containing a nine acid sequences from Nur77 induces Bcl-2 dependent apoptosis in AML. Blood 108(11):2607, 2006.
- Zhang W, Konopleva M, McQueen T, Cortes J, McCubrey J, Andreeff M. Raf inhibitor BAY 43-9006 induces Bim desphosphorylation and activates the intracellular apoptotic pathway in AML. Blood 106:941a, 2005.
- Konopleva M, Zhang W, Ling X, Samudio I, Shi Y-Xi, McQueen T, Tsao T, Meyer C, Munsell MF, Yu D, Safe SH, Hung M-C, Andreeff M. Synthetic triterpenoids CDDO (RTA 401) and CDDO-Me (RTA 402) inhibit HER2-driven growth of breast cancer in vivo. Clin Cancer Res 11S:251, 2005.
- Zhang W, Konopleva M, McQueen T, Schober W, Andreeff M. Induction of cell cycle arrest and apoptosis by dephosphorylation of ERK, Akt and Bcl-2 and phosphorylation of JNK by LY293111 in human anaplastic large cell lymphoma (ALCL). Blood 104:927a, 2004.
- Zhang W, Shi Y-X, McQueen T, Hung M-C, Madden T, Sporn MB, Andreeff M, Konopleva M. Synthetic triterpenoid CDDO as effective therapy for HER2-expressing resistant breast cancer. Proc Am Assoc Cancer Res 45 (#3799) 45(876-877), 2004.
- Zhang W. Histology and pathology of oral cavity. In: The Textbook of Oral Histopathology. People's Health Press, 2000.
- Zhang W. Biopsy procedure in clinical practice of oral medicine. In: Atlas of Practical Diagnoses and Treatment of Oral Diseases. Shandong Press of Science and Technology, 1997.
- Zhang W. Tissue processing and antigen retrieval in immunocytochemistry. In: A Practical Approach to Immunocytochemistry. Shanghai Press of Science and Technology, 1997.
|Title:||The effects of telomerase and p53 expression on oral premalignant lesions with different malignant potential|
|Funding Source:||Shanghai Educational Foundation, China|
|Title:||Effects of cell adhesion molecules E-cadherin and CD44 on the prognosis of salivary gland adenoid cystic carcinoma|
|Funding Source:||Health Ministry of China|
|Title:||Effects of non-collagenous proteins on the formation of biomineralized tissues|
|Funding Source:||Natural Scientific Foundation of China|
|Title:||CDP: Targeting FLT3 mutations in AML with BAY 43-9006 as a therapeutic strategy|
|Title:||CDP: Sorafenib as a novel therapeutic directly targets FLT3-ITD mutation in acute myelogenous leukemia|
|Title:||Phase II Study of Multi-kinase Inhibitor, Sorafenib in Combination with Idarubicin and Cytorabine in Acute Myelogenous Leukemia (AML) and High Risk Myeloidysplastic Syndrome (MDS)|
|Funding Source:||Commonwealth for Cancer Research|