Division of Hematology and Oncology
Department of Internal Medicine
UAMS College of Medicine
Research Interest Statement
Dr. Zhan is interested in understanding how the genetic alterations in cancer cells contribute to tumor progression, alter treatment response and create vulnerabilities that may be targeted therapeutically.
Currently, one of his main focuses is to understand why current clinical trials using monotherapy with PD-1/PD-L1 inhibitors are not successful in treatment of aggressive multiple myeloma (MM) and to develop novel immune therapy by combining NEK2 inhibitors with the PD-L1 blockade to overcome drug resistance in MM. Addressing these questions will reveal new insights into how NEK2 regulates tumor cell survival and suppresses immune responses and may point to therapeutic opportunities relevant to other human cancers.
Another focus is to study CD24 tumor-initiating cell as a novel therapeutic target in myeloma. The objectives of this project are (1) to determine how the CD38+CD45–CD24+ myeloma cells contribute to drug resistance, (2) to define tumor initiating cell features of CD38+CD45–CD24+ primary myeloma cells, such as self-renewal and drug resistance; and 3) to develop tumor-initiating, cell-targeted therapies in myeloma.
Dr. Zhan’s Cancer-related Grants
NIH, National Cancer Institute: 1R01CA236814
Fenghuang Zhan: PI
Title “Novel NEK2 signaling pathways in myeloma progression”
06/01/2020 – 05/31/2025
*annual cancer-related direct cost
NIH, National Cancer Institute: MCW Sub-award
Fenghuang Zhan: PI
Title “Biological Validation of Candidate Myeloma Driver Genes”
01/01/2020 – 06/30/2023
*annual cancer-related direct cost
Leukemia & Lymphoma Society
Fenghuang Zhan: PI
Title “Clinical Investigation of CD38+/Light chain+/CD24+ as Putative Multiple Myeloma Stem Cell Markers”
01/03/2020 – 01/02/2021
*project period cancer-related direct cost
U.S. Department of Defense
Fenghuang Zhan: PI
Title “CD24 Tumor-Initiating Cell as a Novel Therapeutic Target in Myeloma”
04/15/2020 – 11/14/2023
*project period cancer-related direct cost
Dr. Zhan’s UAMS Collaborators
College of Medicine
Department of Internal Medicine
Frits van Rhee, M.D., Ph.D.
Guido Tricot, M.D., Ph.D.
Sarah Johnson, Ph.D.
Donghoon Yoon, Ph.D.
Charles O’Brien, Ph.D.
Department of Pharmacology and Toxicology
Steven Post, Ph.D.
Department of Biochemistry and Molecular Biology
Alan Tackett, Ph.D.
Stephanie Byrum, Ph.D.
Department of Pediatrics
Jin-Ran Chen, Ph.D.
Department of Biostatistics
Eric Siegel, M.S.
Department of Biomedical Informatics
Timothy Cody Ashby, M.S., Ph.D.
UAMS College of Pharmacy
Department of Pharmaceutical Sciences
Hong-yu Li, Ph.D.
Marjan Boerma, Ph.D.
Dr. Zhan’s External Collaborators
Gail A. Bishop, Ph.D., University of Iowa, Iowa City VAMC
Siegfried Janz, M.D., Medical College of Wisconsin
Alexey V. Eliseev, PhD, CEO, Bipharm LLC
Yuwen Zhu, Ph.D., University of Colorado Anschutz Medical Campus
Meng Wu, Ph.D., University of Iowa
Opportunities for Collaboration
I am interested on collaborating with investigators who have interest in cancer immunotherapy.
You May Not Know That …
I am a Los Angeles Lakers fan. I play basketball with my friends every Friday night, except during recent pandemic times.
Recent Cancer-Related Publications
•Gao M, Bai H, Jethava Y, [et al., including Zhan F]. CD24 Is a Phenotypic Marker and a Potential Therapeutic Target for Multiple Myeloma Tumor-Initiating Cells. Journal of the National Cancer Institute. 2019 112(5):507-515.
•Hao M, Barlogie B, Tricot G, [et al., including Zhan F]. Gene Expression Profiling Reveals Aberrant T-cell Marker Expression on Tumor Cells of Waldenstrom?s Macroglobulinemia. Clinical Cancer Research. 2019 25(1):201-209.
•Franqui-Machin R, Hao M, Bai H, [et al., including Zhan F]. Destabilizing NEK2 overcomes resistance to proteasome inhibition in multiple myeloma. The Journal of clinical investigation. 2018 128(7):2877-2893. PMID: 29863498. PMCID: PMC6026005.
•Guo A, Wang Y, Chen B, [et al., including Zhan F]. The E-C coupling structure protein junctophilin-2 encodes a stress-adaptive transcription regulator. Science. 2018 362(6421):1375-1384.
•Hao M, Franqui-Machin R, Xu H, [et al., including Zhan F]. NEK2 induces osteoclast differentiation and bone destruction via heparanase in multiple myeloma. Leukemia. 2017 31(7):1648-1650. PMID: 28400617. PMCID: PMC5508075.
•Xia J, Xu H, Zhang X, [et al., including Zhan F]. Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid. EBioMedicine. 2017 18:41-49. PMID: 28229908. PMCID: PMC5405162.
•Gu Z, Xia J, Xu H, [et al., including Zhan F]. NEK2 Promotes Aerobic Glycolysis in Multiple Myeloma Through Regulating Splicing of Pyruvate Kinase. Journal of hematology & oncology. 2017 10(1):17. PMID: 28086949. PMCID: PMC5237262.
•Huang J, Zhou Y, Thomas GS, [et al., including Zhan F]. NEDD8 Inhibition Overcomes CKS1B-Induced Drug Resistance by Upregulation of p21 in Multiple Myeloma. Clinical cancer research : an official journal of the American Association for Cancer Research. 2015 21(24):5532-42. PMID: 26156395. PMCID: PMC4804624.
•Gu Z, Wang H, Xia J, [et al., including Zhan F]. Decreased ferroportin promotes myeloma cell growth and osteoclast differentiation. Cancer research. 2015 75(11):2211-21. PMID: 25855377. PMCID: PMC4946247.
•Yang Y, Shi J, Gu Z, [et al., including Zhan F]. Bruton tyrosine kinase is a therapeutic target in stem-like cells from multiple myeloma. Cancer research. 2015 75(3):594-604. PMID: 25589346. PMCID: PMC4384656.
•Zhan F, Zangari M, Qiu L. Drug resistance in hematologic malignancies: induction mechanisms, genetics, and therapeutics. BioMed research international. 2015 2015:384575. PMID: 26000289. PMCID: PMC4427090.
•Zhou W, Yang Y, Gu Z, [et al., including Zhan F]. ALDH1 activity identifies tumor-initiating cells and links to chromosomal instability signatures in multiple myeloma. Leukemia. 2014 28(5):1155-8. PMID: 24365790. PMCID: PMC4018236.
•Yang Y, Shi J, Tolomelli G, [et al., including Zhan F]. RAR?2 expression confers myeloma stem cell features. Blood. 2013 122(8):1437-47. PMID: 23847194. PMCID: PMC3750340.
•Veitonmäki N, Hansson M, Zhan F, [et al.]. A human ICAM-1 antibody isolated by a function-first approach has potent macrophage-dependent antimyeloma activity in vivo. Cancer cell. 2013 23(4):502-15. PMID: 23597564.
•Zhou W, Yang Y, Xia J, [et al., including Zhan F]. NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers. Cancer cell. 2013 23(1):48-62. PMID: 23328480. PMCID: PMC3954609.
•Zangari M, Terpos E, Zhan F, Tricot G. Impact of bortezomib on bone health in myeloma: a review of current evidence. Cancer treatment reviews. 2012 38(8):968-80. PMID: 22226939.
•Zangari M, Berno T, Zhan F, [et al.]. Mechanisms of thrombosis in paraproteinemias: the effects of immunomodulatory drugs. Seminars in thrombosis and hemostasis. 2012 38(8):768-79. PMID: 23104518.
•Zangari M, Berno T, Zhan F, [et al.]. Activated protein C resistance as measured by residual factor V after Russell’s viper venom and activated protein C treatment analyzed as a continuous variable in multiple myeloma and normal controls. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2011 22(5):420-3. PMID: 21537162.
•Zangari M, Aujay M, Zhan F, [et al.]. Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients. European journal of haematology. 2011 86(6):484-7. PMID: 21477075.
•Zangari M, Fink L, Zhan F, Tricot G. Low venous thromboembolic risk with bortezomib in multiple myeloma and potential protective effect with thalidomide/lenalidomide-based therapy: review of data from phase 3 trials and studies of novel combination regimens. Clinical lymphoma, myeloma & leukemia. 2011 11(2):228-36. PMID: 21575928.
•Zangari M, Yaccoby S, Pappas L, [et al., including Zhan F]. A prospective evaluation of the biochemical, metabolic, hormonal and structural bone changes associated with bortezomib response in multiple myeloma patients. Haematologica. 2011 96(2):333-6. PMID: 20952514. PMCID: PMC3031705.
•Cruz RD, Tricot G, Zangari M, Zhan F. Progress in myeloma stem cells. American journal of blood research. 2011 1(2):135-45. PMID: 22432075. PMCID: PMC3301427.
•Wu X, Shi J, Wu Y, [et al., including Zhan F]. Arsenic trioxide-mediated growth inhibition of myeloma cells is associated with an extrinsic or intrinsic signaling pathway through activation of TRAIL or TRAIL receptor 2. Cancer biology & therapy. 2010 10(11):1201-14. PMID: 20953137. PMCID: PMC3047108.
•Zangari M, Zhan F, Tricot G. Bone and paraproteinemias. Current opinion in supportive and palliative care. 2010 4(3):195-9. PMID: 20657285.
•Shi L, Wang S, Zangari M, [et al., including Zhan F]. Over-expression of CKS1B activates both MEK/ERK and JAK/STAT3 signaling pathways and promotes myeloma cell drug-resistance. Oncotarget. 2010 1(1):22-33. PMID: 20930946. PMCID: PMC2949973.
•Chen L, Wang S, Zhou Y, [et al., including Zhan F]. Identification of early growth response protein 1 (EGR-1) as a novel target for JUN-induced apoptosis in multiple myeloma. Blood. 2010 115(1):61-70. PMID: 19837979. PMCID: PMC2803692.
•Zangari M, Tricot G, Polavaram L, [et al., including Zhan F]. Survival effect of venous thromboembolism in patients with multiple myeloma treated with lenalidomide and high-dose dexamethasone. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010 28(1):132-5. PMID: 19901114.
•Zangari M, Fink LM, Elice F, [et al., including Zhan F]. Thrombotic events in patients with cancer receiving antiangiogenesis agents. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009 27(29):4865-73. PMID: 19704059.
•van Rhee F, Szmania SM, Dillon M, [et al., including Zhan F]. Combinatorial efficacy of anti-CS1 monoclonal antibody elotuzumab (HuLuc63) and bortezomib against multiple myeloma. Molecular cancer therapeutics. 2009 8(9):2616-24. PMID: 19723891. PMCID: PMC2748787.
•Wang S, Tricot G, Shi L, [et al., including Zhan F]. RARalpha2 expression is associated with disease progression and plays a crucial role in efficacy of ATRA treatment in myeloma. Blood. 2009 114(3):600-7. PMID: 19458357. PMCID: PMC2713470.
•Wang S, Tricot G, Shi L, [et al., including Zhan F]. RARa2 expression is associated with disease progression and plays a crucial role in efficacy of ATRA treatment in myeloma. Blood. 2009 114(3):600-607.
•Xiong W, Wu X, Starnes S, [et al., including Zhan F]. An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma. Blood. 2008 112(10):4235-46. PMID: 18337559. PMCID: PMC2581979.
•Hsi ED, Steinle R, Balasa B, [et al., including Zhan F]. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clinical cancer research : an official journal of the American Association for Cancer Research. 2008 14(9):2775-84. PMID: 18451245. PMCID: PMC4433038.
•Yaccoby S, Pennisi A, Li X, [et al., including Zhan F]. Atacicept (TACI-Ig) inhibits growth of TACI(high) primary myeloma cells in SCID-hu mice and in coculture with osteoclasts. Leukemia. 2008 22(2):406-13. PMID: 18046446. PMCID: PMC2771378.
•Zhan F, Barlogie B, Mulligan G, [et al.]. High-risk myeloma: a gene expression based risk-stratification model for newly diagnosed multiple myeloma treated with high-dose therapy is predictive of outcome in relapsed disease treated with single-agent bortezomib or high-dose dexamethasone. Blood. 2008 111(2):968-969.
•Haessler J, Shaughnessy JD Jr, Zhan F, [et al.]. Benefit of complete response in multiple myeloma limited to high-risk subgroup identified by gene expression profiling. Clinical cancer research : an official journal of the American Association for Cancer Research. 2007 13(23):7073-9. PMID: 18056185.
•Szmania S, Gnjatic S, Tricot G, [et al., including Zhan F]. Immunization with a recombinant MAGE-A3 protein after high-dose therapy for myeloma. Journal of immunotherapy (Hagerstown, Md. : 1997). 2007 30(8):847-54. PMID: 18049337.
•Li X, Pennisi A, Zhan F, [et al.]. Establishment and exploitation of hyperdiploid and non-hyperdiploid human myeloma cell lines. British journal of haematology. 2007 138(6):802-11. PMID: 17760811. PMCID: PMC2748973.
•Qian J, Xie J, Hong S, [et al., including Zhan F]. Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in multiple myeloma. Blood. 2007 110(5):1587-94. PMID: 17515399. PMCID: PMC1975842.
•Annunziata CM, Davis RE, Demchenko Y, [et al., including Zhan F]. Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma. Cancer cell. 2007 12(2):115-30. PMID: 17692804. PMCID: PMC2730509.
•Zhan F, Colla S, Wu X, [et al.]. CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms. Blood. 2007 109(11):4995-5001. PMID: 17303695. PMCID: PMC1885527.
•Colla S, Zhan F, Xiong W, [et al.]. The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Blood. 2007 109(10):4470-7. PMID: 17255354. PMCID: PMC1885505.
•Shaughnessy JD Jr, Zhan F, Burington BE, [et al.]. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007 109(6):2276-84. PMID: 17105813.
•Yaccoby S, Ling W, Zhan F, [et al.]. Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood. 2007 109(5):2106-11. PMID: 17068150. PMCID: PMC1801040.
•Zhan F, Barlogie B, Arzoumanian V, [et al.]. Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis. Blood. 2007 109(4):1692-700. PMID: 17023574. PMCID: PMC1794073.
•Prasad HK, Zhan F, Shaugnessy J. Smoldering multiple myeloma. New England Journal of Medicine. 2007 357(10):1048.
•Zhan F, Huang Y, Colla S, [et al.]. The molecular classification of multiple myeloma. Blood. 2006 108(6):2020-8. PMID: 16728703. PMCID: PMC1895543.
•Hanamura I, Stewart JP, Huang Y, [et al., including Zhan F]. Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood. 2006 108(5):1724-32. PMID: 16705089. PMCID: PMC1895503.
•Carrasco DR, Tonon G, Huang Y, [et al., including Zhan F]. High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. Cancer cell. 2006 9(4):313-25. PMID: 16616336.
•Ge Y, Zhan F, Barlogie B, [et al.]. Fibroblast activation protein (FAP) is upregulated in myelomatous bone and supports myeloma cell survival. British journal of haematology. 2006 133(1):83-92. PMID: 16512833.
•Bergsagel PL, Kuehl WM, Zhan F, [et al.]. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood. 2005 106(1):296-303. PMID: 15755896. PMCID: PMC1895118.
•van Rhee F, Szmania SM, Zhan F, [et al.]. NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses. Blood. 2005 105(10):3939-44. PMID: 15671442. PMCID: PMC1895070.
•Santin AD, Zhan F, Cane’ S, [et al.]. Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy. British journal of cancer. 2005 92(8):1561-73. PMID: 15785748. PMCID: PMC2362016.
•Santin AD, Zhan F, Bignotti E, [et al.]. Gene expression profiles of primary HPV16- and HPV18-infected early stage cervical cancers and normal cervical epithelium: identification of novel candidate molecular markers for cervical cancer diagnosis and therapy. Virology. 2005 331(2):269-91. PMID: 15629771.
•Santin AD, Zhan F, Bellone S, [et al.]. Gene expression profiles in primary ovarian serous papillary tumors and normal ovarian epithelium: identification of candidate molecular markers for ovarian cancer diagnosis and therapy. International journal of cancer. 2004 112(1):14-25. PMID: 15305371.
•Santin AD, Zhan F, Bellone S, [et al.]. Discrimination between uterine serous papillary carcinomas and ovarian serous papillary tumours by gene expression profiling. British journal of cancer. 2004 90(9):1814-24. PMID: 15208622. PMCID: PMC2409747.
•Tian E, Zhan F, Walker R, [et al.]. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. The New England journal of medicine. 2003 349(26):2483-94. PMID: 14695408.
•Kelly T, Miao HQ, Yang Y, [et al., including Zhan F]. High heparanase activity in multiple myeloma is associated with elevated microvessel density. Cancer research. 2003 63(24):8749-56. PMID: 14695190.
•Batchu RB, Moreno AM, Szmania S, [et al., including Zhan F]. High-level expression of cancer/testis antigen NY-ESO-1 and human granulocyte-macrophage colony-stimulating factor in dendritic cells with a bicistronic retroviral vector. Human gene therapy. 2003 14(14):1333-45. PMID: 14503968.
•Shaughnessy J, Jacobson J, Sawyer J, [et al., including Zhan F]. Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression. Blood. 2003 101(10):3849-56. PMID: 12531801.
•Zhan F, Tian E, Bumm K, [et al.]. Gene expression profiling of human plasma cell differentiation and classification of multiple myeloma based on similarities to distinct stages of late-stage B-cell development. Blood. 2003 101(3):1128-40. PMID: 12393520.
•Zhan F, Hardin J, Kordsmeier B, [et al.]. Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells. Blood. 2002 99(5):1745-57. PMID: 11861292.
•Shaugnessy J, Gabrea A, Yi Q, [et al., including Zhan F]. Cyclin D3 at 6p21 is downregulated by recurrent Ig translocations in multiple myeloma. Blood. 2001 98(1):217-223.