Department of Internal Medicine

Hematology, Oncology and Blood & Marrow Transplantation Faculty

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Fenghuang Zhan, M.D, Ph.D.
Professor

The long-term objective of Dr. Zhan’s lab is to develop novel therapies to overcome drug resistance and deplete cancer stem cells in myeloma. The major focus of research in Dr. Zhan laboratory is to define genes that make some myeloma cells resistant to chemotherapy and confirm their findings by  in vitro (myeloma cell lines and primary myeloma cells) as well as in vivo (Mouse models).

Honors, Awards and Organizations

• American Society of Hematology
• American Association of Cancer Research
• Senior Research Award, Multiple Myeloma Research Foundation, 2008
• Senior Research Award, Multiple Myeloma Research Foundation, 2010
• Translational Research Program, Leukemia & Lymphoma Society, 2010
• R01, National Cancer Institute, 2010
• R21, National Cancer Institute, 2010
• Translational Research Program, Leukemia & Lymphoma Society, 2012

Links of Interest

• Gene Promotes Drug Resistance in Cancer (Science Daily)

Select Publications (of 91)

• Zhou W, Yang Y, Xia J, Wang H, Salama M , Xiong W, Xu H, Shetty S, Miles R, Shi L, Zeng Z, Chen T, Bearss D, Tricot G, and Zhan F *(correspondence). Targeting NEK2, a chromosomal instability gene, to overcome drug-resistance in myeloma and other cancers. Cancer Cell.  2013, 23(1):48-62.
• Zangari M, Berno T, Zhan F, Tricot G, Fink L. Mechanisms of thrombosis in paraproteinemias: the effects of immunomodulatory drugs. Semin Thromb Hemost. 2012, 38(8):768-79
• Wu X, Shao Y, Tao Y, Ai G, Wei R, Meng X, Hou J, Han Y, Zhan F, Zheng J, Shi J. Proteasome inhibitor lactacystin augments natural killer cell cytotoxicity of myeloma via downregulation of HLA class I. Biochem Biophys Res Commun. 2011, 11; 415(1):187-92.
• Cruz RD, Tricot G, Zangari M, Zhan F. Progress in myeloma stem cells. Am J Blood Res. 2011,1(2):135-45.
• 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.  Clin Lymphoma Myeloma Leuk. 2011, 11(2):228-36.
• Zangari M, Yaccoby S, Pappas L, Cavallo F, Kumar NS, Ranganathan S, Suva LJ, Gruenwald JM, Kern S, Zhan F.   Esseltine DL, Tricot G. A prospective evaluation of the biochemical, metabolic, hormonal and structural bone changes associated with bortezomib response in multiple myeloma patients.Haematologica. 2011, 96(2):336-6.
• Wu X, Shi J, Wu Y, Meng X, Hou J, Hu X, Han Y, Jiang W, Tang S, Zangari M, Tricot G, and  Zhan F     (correspondence).  Arsenic trioxide-mediated growth inhibition of myeloma cells is associated with an extrinsic of  intrinsic signaling pathway  through activation of TRAIL or TRAIL receptor 2. Cancer Biology & Therapy. 2010, 20;10(11).
• Shi L, Wang S, Zangari M,  Xu H, Cao T, Xu C, Wu Y, Xiao F, Liu Y, Yang Y,  Li G, Tricot G and  Zhan F  (correspondence). 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.
• Zangari M, Tricot G, Polavaram L, Zhan F, Finlayson A, Knight R, Fu T, Weber D, Dimopoulos  MA,  Niesvizky R, Fink L. Survival effect of venous thromboembolism in patients with multiple myeloma treated with lenalidomide and high-dose dexamethasone. J Clin Oncol. 2010; 28(1):132-5.
• Chen L, Wang S , Zhou Y, Wu X, Entin I, Epstein J, Yaccoby S, Xiong W, Barlogie B, Shaughnessy Jr. J and Zhan F (correspondence). 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.
• Zangari M, Fink LM, Elice F, Zhan F, Adcock DM, Tricot GJ. Thrombotic Events in Cancer Patients Receiving Antiangiogenesis Agents. J Clin Oncol. 2009, 27(29):4865-73.
• Anguiano A, Tuchman SA, Acharya C, Salter K, Gasparetto C, Zhan F, Dhodapkar M, Nevins J, Barlogie B, Shaughnessy JD Jr, Potti A. Gene Expression Profiles of Tumor Biology Provide a Novel Approach to Prognosis and May Guide the Selection of Therapeutic Targets in Multiple Myeloma. J Clin Oncol. 2009, 27(25):4197-203.
• Wang S, Tricot G, Shi L, Xiong W, Zeng Z, Xu H, Zangari M, Barlogie B, Shaughnessy Jr J and Zhan F (correspondence).  RARa2 expression is associated with disease progression and plays a crucial role in efficacy of ATRA treatment in myeloma.  Blood, 2009, 114(3): 600-7.
• Brenne AT, Fagerli UM, Shaughnessy J, Vatsveen TK, Ro TB, Hella H, Zhan F, Barlogie B, Sundan A, Borset M, Waage A. High expression of BCL3 in human myeloma cells is associated with increased proliferation and inferior prognosis.  Eur J Haematol. 2009, 82(5):354-363.
• Burington B, Barlogie B, Zhan F, Crowley J, Shaughnessy JD Jr. Tumor cell gene expression changes following short-term in vivo exposure to single agent chemotherapeutics are related to survival in multiple myeloma. Clin Cancer Res. 2008, 14(15):4821-9.
• Zhan F (correspondence), Barlogie B, Mulligan G, Shaughnessy Jr. J, and Bryant B. 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. Blood, 2008,111(2):968-9..
• Xiong W, Wu X, Starnes S, Johnson SK,  Haessler J,  Wang S, Chen L, Barlogie B,  Shaughnessy Jr. J, and  Zhan F (correspondence). An analysis of the clinical and biological significance of TP53 loss in multiple myeloma and the identification of potential novel transcriptional targets of TP53. Blood, 2008, 112(10):4235-46.
• Yang Y, Macleod V, Miao HQ, Theus A, Zhan F, Shaughnessy JD Jr, Sawyer J, Li JP, Zcharia E, Vlodavsky I,   Sanderson RD. Heparanase enhances syndecan-1 shedding: A novel mechanism for stimulation of tumor growth and metastasis. J Biol Chem. 2007, 282(18):13326-33.
• Claudio JO, Zhan F, Zhuang L, Khaja R, Zhu YX, Sivananthan K, Trudel S, Masih-Khan E, Fonseca R, Bergsagel PL, Scherer SW, Shaughnessy J, Stewart AK.  Expression and mutation status of candidate kinases in multiple myeloma. Leukemia. 2007, 21(5):1124-7.
• Zhan F(co-correspondence), Colla1 S, Wu X, Chen JB ,Stewart JP, Kuehl WM, Barlogie B and Shaughnessy, Jr.  CKS1B, Over Expressed in Aggressive Disease, Regulates Multiple Myeloma Growth and Survival through SKP2- and p27Kip1-Dependent and Independent Mechanisms.  Blood, 2007,109 (11): 4995-5001.  
• Colla S, Zhan F (co-1st author), Xiong W, Wu X, Xu H, Stephens O, Yaccoby S, Epstein J, Barlogie B and Shaughnessy Jr. Oxidative stress response regulates DKK1 expression through JNK signaling cascade in multiple myeloma plasmacells.  Blood, 2007,109(10):4470-7.
• Yaccoby S, Pennisi A, Li X, Dillon SR, Zhan F, Barlogie B, Shaughnessy JD Jr. 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.
• Prasad HK, Zhan F, Shaughnessy J: Smoldering multiple myeloma, N Engl J Med. 2007, 357:1048;
• Park ES, Lee JS, Woo HG, Zhan F, Shih JH, Shaughnessy JD, Frederic Mushinski J.  Heterologous tissue culture expression signature predicts human breast cancer prognosis.  PLoS ONE. 2007,2:145.
• Mulligan G, Mitsiades C, Bryant B, Zhan F, Chng WJ, Roels S, Koenig E, Fergus A, Huang Y, Richardson P, Trepicchio WL, Broyl A, Sonneveld P, Shaughnessy JD Jr, Bergsagel PL, Schenkein D, Esseltine DL, Boral A, Anderson KC.  Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib. Blood, 2007,109(8):3177-88.
• Annunziata CM, Davis RE, Demchenko Y, Bellamy W, Gabrea A, Zhan F, Lenz G, Hanamura I, Wright G, Xiao W, Dave S, Hurt EM, Tan B, Zhao H, Stephens O, Santra M, Williams DR, Dang L, Barlogie B, Shaughnessy JD Jr, Kuehl WM, Staudt LM. Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell. 2007,12(2):115-30.
• Qian J, Xie J, Hong S, Yang J, Zhang L, Han X, Wang M, Zhan F, Shaughnessy JD Jr, Epstein J, Kwak LW, Yi Q. Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in multiple myeloma. Blood. 2007, 110(5):1587-94.
• Zhan F (correspondence), Barlogie B, John D S Jr. Gene expression profiling defines a high-risk entity of multiple myeloma.  Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2007, 32(2):191-203.
• Zhan F, Barlogie B, Arzoumanian V, Huang Y, Dhodapkar M and Shaughnessy Jr. J.  A gene expression signature of being monoclonal gammopathy evident in multiple myeloma is linked to good prognosis. Blood 2007, 109(4):1692-700.
• Yaccoby S, Ling W, Zhan F, Walker R, Barlogie B, Shaughnessy Jr JD.. Antibody-based inhibition of DKK1 suppresses tumor- induced bone resorption and multiple myeloma growth in- vivo. Blood, 2007, 109(5):2106-11
• Shaughnessy Jr JD, Zhan F, Burington BE, Huang Y, Colla S, Hanamura I, Stewart JP, Kordsmeier B, Randolph C, Williams DR, Xiao Y, Xu H, Epstein J, Anaissie E, Krishna SG, Cottler-Fox M, Hollmig K, Mohiuddin A, Pineda-Roman M, Tricot G, van Rhee F, Sawyer J, Alsayed Y, Walker R, Zangari M, Crowley J, Barlogie B..  Deregulated Expression of Chromosome 1 Genes Defines High-Risk Multiple Myeloma.  Blood, 2007, 109(6):2276-84.
• Zhan F, Sawyer J, and Tricot G.  The role of cytogenetics in myeloma.  Leukemia. 2006, 20:1484-6.
• Zhan F, Huang Y, Colla S, Stewart JP, Hanamura I, Gupta S, Epstein J, Yaccoby S, Sawyer J, Burington B, Hollmig K, Pineda-Roman M, Tricot G, van Rhee F, Walker R, Zangari M, Crowley J, Barlogie B, Shaughnessy Jr JD.  The molecular classification of multiple myeloma.  Blood. 2006, 108(6):2020-8.
• Hanamura I, Stewart JP, Huang Y, Zhan F, Santra M, Sawyer J, Hollmig K, Zangari M, Pineda-Roman M, van Rhee F, Cavallo F, Burington B, Crowley J, Tricot G, Barlogie, B, Shaughnessy JD.  Frequent gain of chromosome band 1q21 in plasma cell dyscrasias detected by Fluoresence in situ hybridization: incidence increase from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem cell transplantation.  Blood. 2006, 108(5):1724-32.
• Carrasco DR, Tonon G, Huang Y, Zhang Y, Sinha R, Feng B, Stewart JP, Zhan F, Khatry D, Protopopova M, Protopopov A, Sukhdeo K, Hanamura I, Stephens O, Barlogie B, Anderson KC, Chin L, Shaughnessy JD Jr, Brennan C, Depinho RA.  High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple  myeloma patients. Cancer Cell. 2006, 9:313-25.
• Bergsagel PL, Kuehl M, Zhan F, Sawyer J, Barlogie B, and Shaughnessy J.  Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma.  Blood. 2005,98:217-23.
• Van Rhee F, Szmania S, Zhan F, Gupta S, Pomtree M, Lin P, Batchu RB, Moreno A, Spagnoli G, Shaughnessy J, and Tricot G.  NY-ESO-1 is highly expressed in poor prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses.  Blood, 2005, 105:3939-44.
• Maxwell CA, Rasmussen E, Zhan F, Keats JJ, Adamia S, Strachan E, Crainie M, Walker R, Belch AR, Pilarski LM, Barlogie B, Shaughnessy J Jr, Reiman T.  RHAMM expression and isoform balance predict aggressive disease and poor survival in multiple myeloma.  Blood. 2004, 104:1151-8.
• Tian E, Zhan F(co-1st author), Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr.  The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma.  N Engl J Med. 2003, 349:2483-94.
• Zhan F, Barlogie B and Shaughnessy Jr. J.  Toward the Identification Distinct Molecular and Clinical Entities of Multiple Myeloma Using Global Gene Expression Profiling.  Semin  Hematol. 2003, 40: 308-20.(Review)
• Tarte K, Zhan F, De Vos J, Klein B, Shaughnessy J Jr. Gene expression profiling of plasma cells and plasmablasts: toward a better understanding of the late stages of B-cell differentiation.  Blood. 2003, 102: 592-600.
• Santra M, Zhan F, Tian E, Barlogie B, Shaughnessy J Jr. A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript. Blood,  2003 ;15:2374-6.
• Shaughnessy J, Jacobson J, Sawyer J, McCoy J, Fassas A, Zhan F, Bumm K, Epstein  J, Anaissie E, Siegel D, Desikan R, Munshi N, Badros A, Tian E, Zangari M, Tricot G, Crowley J, Barlogie B.   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, 101:3849-56.
• Zhan F, Erming Tian, Bumm K,  Smith R, Barlogie B, and Shaughnessy J. 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, 101:1128-40.
• Tarte K, De Vos J, Thykjaer T, Zhan F, Fiol G, Costes V, Reme T, Legouffe E, Ross J-F, Shayghnessy J, Orntoft T, and Klein B.  Generation of polyclonal plasma cells from peripheral blood B cells : a normal counterpart of malignant plasma cells.  Blood, 2002, 100: 592-600.
• Zhan F, Hardin J, Bumm K, Zheng M, Tian E, Sanderson R, Yang Y, Wilson C, Zangari M, Anaissie E, Morris C, Muwalla F, Van Rhee F, Fassas A, Tricot G, Crowley J, Barlogie B, and Shaughnessy J. Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance and normal bone marrow plasma cells. Blood, 2002,  99:1745-57.
• Bumm K, Zheng M, Baily C, Zhan F, Eddlemon P, Terry J,  Barlogie B , Shaughnessy J. CGO: utilizing and integrating gene expression microarray data in clinical research and data management.  Bioinformatics. 2002, 18:327-8.
• Shaughnessy , J, Gabrea A, Yi, Q, Brents, L, Zhan F, Tian E, Sawyer J, Barlogie B, BergsAgel PL, Kuehl M.  Cyclin D3 at 6p21 is downregulated by recurrent Ig translocations in multiple myeloma. Blood. 2001,  98: 217-23.

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