Zhan Fh, born in 1966, Professor Zhan Fh, a famous tumor molecular scientist, was born in Miluo City, Hunan Province. He received his doctorate in tumor molecular genetics from Hunan Medical University and studied in the United States as an outstanding scholar. Postdoctoral fellow at the University of Arkansas School of Medicine, currently an associate professor at the University of Utah School of Medicine, director of the Center for Blood and Bone Marrow Transplantation at the University of Utah, and distinguished professor at the Cancer Institute of Southern Medical University.
Chinese name: Zhan Fh.
Mbth: zhanFH
Nationality: Chinese American
Ethnic group: Han nationality
Place of birth: Miluo, Hunan
Date of birth: 1966
Occupation: professor, doctoral supervisor, research director
Graduate school: Hunan Medical University
Main achievements: It is at the international leading level in myeloma research.
Representative works: He has undertaken many fund projects such as NIHRO 1 and R2 1, and published more than 70 papers in international authoritative journals.
Character experience
June 65438+July 0989, graduated from Hunan Medical University, majoring in stomatology. June 65438+July 0990, graduated from West China University of Medical Sciences, majoring in stomatology. July1990-August 1993, clinical physician, Department of Stomatology, Xiangya Hospital, Hunan Medical University. 1September 1993 to1July 1996, studied for a master's degree in oral surgery at Xiangya Hospital of Hunan Medical University. 1July, 1996 to1March, 1999, he studied for a doctorate in the Institute of Cancer, Hunan Medical University, and obtained a doctorate. 1March, 1999 to1February, 1999, he was employed as a postdoctoral researcher at the University of Floreville, and his family immigrated to the United States. From June 2000 to June 2002, she was a postdoctoral researcher in pharmaceutical science research at the University of Far Kansas. From 2002 to 2008, he served as an assistant professor and associate professor at the University of Arkansas School of Medicine. In 2008, he served as an associate professor at the University of Utah School of Medicine and director of the Center for Blood and Bone Marrow Transplantation. In China, he served as a visiting professor at Central South University. 20 10 served as distinguished professor, doctoral supervisor and director of the institute of oncology of southern medical university. Director, Center for Blood and Bone Marrow Transplantation, University of Utah. Now he is a member of American Hematology Association, and he is a reviewer of many international journals and magazines such as Blood, DNACellBiol, JCancerResClin, JClinInvest and HumanPathology.
research direction
Dr Zhan Fh is mainly engaged in the research of multiple myeloma.
Main contribution
He undertook many fund projects such as NIHRO 1 and R2 1, and applied for 4 patent projects. He has published more than 70 papers in internationally renowned magazines such as NEnglJMed and Blood, and his research in the field of blood and bone marrow transplantation is at the international leading level.
Multiple myeloma is a malignant tumor with abnormal plasma cell proliferation. Its incidence rate ranks second among hematological malignancies, and its prognosis is poor. MM patients have genetic heterogeneity and long survival time span. According to the data provided by NIH, its 5-year survival rate has been hovering around 30% in recent 10 years. Since 2000, Dr. Zhan Fh has made a thorough and systematic study on the etiology and pathogenesis of myeloma by means of molecular biology, molecular genetics and cell biology, and has made great achievements in the whole genome expression characteristics and changing rules, related gene functions, molecular marker screening, molecular typing standards, and the establishment of diagnosis and treatment system in the multi-stage pathogenesis of myeloma. Through the joint efforts of Dr. Zhan and his colleagues, the five-year survival rate of myeloma patients in his unit has reached 60%. The main research achievements of Dr. Zhan in the past five years are as follows:
1. It was found that the up-regulation of DKK 1 gene expression was related to osteolytic lesions in myeloma patients, and it was also found that thalidomide and lenalidomide, commonly used drugs in clinical treatment of myeloma, could induce apoptosis of myeloma cells through JNK pathway.
(1) By establishing a large-scale gene chip hybridization and data analysis technology platform, it was found that the increase of DKK 1 gene expression was closely related to the osteolytic process of myeloma patients, which further confirmed that secreted DKK 1 could affect the differentiation of osteoblasts by inhibiting WNT pathway, and clarified the mechanism of DKK 1 in the osteolytic process of myeloma patients. This paper was published in Nengjmed 200349: 2483-94 (if _ .833; Tied for the first author). In this issue, the magazine also published a special review article: new insights into the formation of osteolysis in multiple myeloma. Nengljmed.2003，349 (26): 2479-80)。
(2) It was found that thalidomide and lenalidomide, which are commonly used in clinic, can up-regulate the expression of DK 1 by activating JNK signal transduction pathway, which provided a theoretical basis for further study on JNK pathway to treat myeloma patients and prevent osteolytic lesions (Blood, Jan 30, 2007, tied for the first author).
2. By analyzing the large-scale gene expression profiles of normal people and myeloma patients, different subtypes of myeloma patients and their characteristic gene expression profiles are determined, which provides a theoretical basis for the formulation of individualized treatment plans for myeloma patients.
The genome-wide gene expression profiles of 74 myeloma patients, 5 myeloma precancerous lesions (MGUS) and 3 1 normal control bone marrow cells were analyzed for the first time. Through cluster analysis, it is found that there are four subtypes in myeloma patients, and many genes are related to prognosis and drug resistance (Blood, 2002, 99: 1745-57, the first author, this is the first one. To this end, the magazine published a special review article: Defining gene diagnosis. blood.2002，99 (5): 1504。 Subsequently, through further in-depth study, myeloma was further subdivided into seven subtypes, and the prognosis, characteristic genes and cytogenetic changes of each subtype were determined, which pointed out the direction for individualized treatment of clinical myeloma patients (Blood2005 2005, 106: 296-303, the first author; Cancer Cell, 2006, 9:3 13-25).
3. By studying the gene expression profile of myeloma in different differentiation stages, the relationship between the occurrence and development of myeloma and the expression of characteristic genes and B cell differentiation was determined, which laid a solid foundation for the screening of molecular markers for prognosis prediction of myeloma and the establishment of molecular typing standard system.
(1) By cluster analysis of gene expression profiles of normal people, precancerous lesions and myeloma patients, it was found that the gene expression profiles of some patients with good prognosis were similar to those of precancerous lesions. This provides a genetic basis for explaining the huge difference in survival time of myeloma patients. (Blood 2007 109: 1692-700, first author).
(2) By studying the gene expression profiles of plasma cells and myeloma cells at different stages of differentiation, 30 genes related to late differentiation of B cells were screened and identified, which can be used to formulate the criteria for molecular typing of myeloma. (Blood, 2003,101:128-1140, the first author, the cover article of this issue; Blood, 2003, 15, 102:592-600).
(3) Closely combining with clinical data, classifying according to clinical indications, comparing and analyzing gene expression profiles, and finding out the genes related to patients' short-term death. According to the expression of these genes, the risk factors and prognosis of patients can be predicted. According to the function of these genes, different treatment schemes can be formulated: directly inhibiting the growth and differentiation of tumors, or indirectly overcoming the drug resistance of patients. It brings hope for the treatment of patients with clinical intractable diseases. (Blood2006 109:2276-84, first author).
4. Through in-depth study of gene function, it is proved that CKS 1B is an oncogene closely related to the pathogenesis of myeloma.
On the basis of the above-mentioned high-risk genes related to myeloma, through the in-depth study of gene functions, it is found that CKS 1B promotes the proliferation and malignant biological behavior of myeloma cells through SKP2 and p27(kip 1) dependent and independent ways, and it is an oncogene closely related to the pathogenesis of myeloma. It laid a theoretical foundation for the establishment of CKS 1B targeted inhibition therapy for high-risk patients with multiple myeloma. (Blood 2007 Mar 15, Epubahedofprint, first author)
5. Study on the whole genome expression characteristics and changes of other malignant tumors such as cervical cancer and ovarian cancer.
Dr. Zhan Fh not only made a breakthrough in the study of myeloma, but also successfully applied the established Qualcomm chip hybridization and data analysis technology platform to the study of the whole genome expression characteristics and changing rules of other tumors such as cervical cancer and ovarian cancer, and achieved some important research results, and published a series of research papers (BrJCancer, 2005,92 (8):1561-73). Virology, 2005,331(2): 269-91; IntJCancer，2004， 1 12( 1): 14-25； BrJCancer，2004，90(9): 18 14-24； Both are second authors).
6. Instruct patients with myeloma to adopt all-trans retinoic acid individualized treatment.
Through gene expression profile analysis, 30% patients with multiple myeloma expressed RARa2 gene, and the prognosis of such patients was poor. RARa2 is a receptor on the nuclear membrane of retinoic acid. If the myeloma cell RARa2 is positive, all-trans retinoic acid can be used to treat such patients, thus guiding tumor cell apoptosis and differentiation (Blood2009；; On May 20th, Epubaheadofprint correspondent).
research subject
The projects supported by the American Research Fund are as follows (* * * about US$ 5.4 million):
Overexpression of 1.R0 1, CA 152 105, 07/01106/3015nek2 led to drug-resistant myeloma. Direct cost: $65,438+$250,000, total cost: $65,438+$868,750, National Cancer Institute, role: chief investigator.
2.R2 1，CA 143887，07/0 1/ 10 _ 06/30/ 12， Retinoidbasedtreatment approach: $275,000, total cost: $412625, National Cancer Institute, role: PrincipalInvestigator.
3.LLS,10/0110 _ 09/30/13 Target nek 2 inmmtooveredrug-resistance, direct cost: 540,000 USD, total cost: 600,000 USD.
4.R0 1, CA 1 15399, 07/01/07 _ 06/30/12 Gene ExpressionProfiling VS MRDassementinmyelmanian InstituteOf Health, total cost:.
5. mmrfsenior 2010,08/0110 _ 07/30/12ar2-ExpressionMyelomyelomaResearch DirectCosts: $180.
6.LLS,10/0111_ 09/30/14, targeting CKS1b-scfcomplex aggressive myeloma, direct cost: USD 540,000.
Leukemia Lymphocyte Society, Role: Principal Investigator
7.CRR_HCIofUU，07/0 1/ 1 1 _ 06//30/ 12
Direct cost: $50,000
Role: Chief Investigator
8. University of Florida, 05/0112 ~ $65,438+0,000,000 institutional start-up fund, Department of International Medicine, University of Florida and Holden Comprehensive Concert Center, position: chief investigator.
The most representative paper
1.ChenL，WangS，ZhouY，WuX，EntinI，EpsteinJ，YaccobyS，XiongW，BarlogieB，ShaughnessyJr。 JandZhanF (correspondence). To identify Arlygrowthresponpotein1(EGR-1) as a new target for jun _ inducedapoptosisin multiple myeloma. blood . 20 10 Jan 7 1 15( 1):6 1-70。
2.WuX, ShiJ, WuY, MengX, HouJ, HuX, HanY, JiangW, TangS, ZangariM, TricotG, andZhanF (corresponding). arsenictrioxide-mediatedgrowthinhibitionofyelomacellsiassociatedwithanextrinsicofintricsignalingpathwaythroughactivationoftrailortraireceptor 2。 Cancer biology and medicine. therapy . 20 10 dec 20 10( 1 1)。
3.ShiL, WangS, ZangariM, XuH, CaoT, XuC, WuY, XiaoF, LiuY, YangY, LiG, TricotGandZhanF (corresponding). Overexpression of fcks1bactivatesbothmek/erkandjak/stat 3 signal pathway and promotion of drug resistance of bone marrow cells. OncoTarget，20 10 1( 1):22-33。
4. Wang, TricotG, ShiL, XiongW, ZengZ, XuH, ZangariM, BarlogieB, ShaughnessyJrJandZhanF (corresponding). Rara 2 ExpressionAssociatedwithiadiediestorogression and PlaySacrucial Rolefinificacy of Fatratementmyeloma. Blood, 2009 1 14(3):600-7.
5.ZhanF (Communication), BarlogieB, MulliganG, Shaughnessy Jr. j、andBryantB。 AGeneExpression-based driskstrationmodelfornewlydiagnostedmultiplemyelomateredatedwithdhighdosetherapyispredictiveoutcomeinrelapseddisease treatedwithsingagentbortezomib。 Blood, 2008111(2): 968-9.
6.XiongW，WuX，StarnesS，JohnsonSK，HaesslerJ，WangS，ChenL，BarlogieB，ShaughnessyJr。 j， AndZhanF (communication) . analysis of clinical and biological significance of p53 lossin multiplemyeloma and eidentification of potentials noveltranscriptiontargetsoft p53 . b lood，2008 1 12( 10):4235-46 .
7.ZhanF (correspondence), Colla 1S, WuX, ChenJB, StewartJP, KuehlWM, BarlogieBandShaughnessy, Jr.CKS 1B, Overexpressed Radiological Disease, Regulated multiplemyelogrowth and Survivalthroughskp2-and 27 kip 1-dependent and dependentMechanisms. Blood, 2007109 (11): 4995-5001.
8.ZhanFH (Communication), BarlogieB, JohnDSJr. genexpressionprofilindefinesahigh-risentityofmultiplemyeloma . 200732(2): 19 1-203。
9.ZhanF，BarlogieB，ArzoumanianV，HuangY，DhodapkarMandShaughnessyJr。 j . ageneexpressionsignatureofbeingmonoclonalgampathyedentinmultiplemyelomaislinktedtogoodprediction . blood 2007 109(4): 1692-700。
10. Janff, Sawyer and Tricot. Leukemia. 200620: 1484-6。
1 1. Zhanfu, Huang Yi, Colas, Stewatip, Hanamuray, Guptas, Crowley, Balocchi Bu, shaughnessy Ijed. Molecular classification of multiple myeloma.