Head of Department & Chair Professor of Biomedical Science
Benjamin photo
Benjamin Yat Ming Yung       

  • Postdoctoral Fellow of Professor Arthur Kornberg (Nobel Laureate of Physiology and Medicine, 1959), Department of Biochemistry, Stanford University School of Medicine, Stanford, California, 1986-1989
  • Ph.D., Dept. of Pharmacology, Baylor College of Medicine, Texas, USA,1986
  • MA,  Dept. of Chemistry, Rice University, Texas, USA, 1982
  • BA, Dept. of Chemistry, Southern Illinois University at Carbondale, Illinois, USA, 1980
Academic Position
2009 - Now Head & Chair Professor, Department of Health Technology & Informatics
2008 - 2009 Associate Head (Research) & Chair Professor, Department of Health Technology & Informatics
2006-2008 Director and Head, Graduate Institute of Natural Products, College of Medicine, Chang Gung University
2001-2006 Dean, Office of Research and Development, Chang Gung University
1993- 2008 Professor, Dept. of Pharmacology, College of Medicine, Chang Gung University
1989- 1993 Associate Professor, Department of Pharmacology, College of Medicine, Chang Gung University
1986-1989      Postdoctoral Fellow of Professor Arthur Kornberg (Nobel Laureate of Physiology and Medicine, 1959) Dept. of Biochemistry, Stanford University, California, USA
Academic Honors, Awards and Membership
2003 Research Excellence Award, Chang Gung University
1999 Outstanding Cancer Research Award from Chinese Oncology Society, R.O.C.
1999 Outstanding Research Award from Pharmacological Society, R.O.C.
1995 – 2006 National Science Council Research Award
1993 – 1994 National Science Council Outstanding Research Award
1990 – 1992 National Science Council Excellent Performance Research Award
1993     Ministry of Education Outstanding Teacher Award
1985   

Busch Award from Baylor College of Medicine
(Outstanding Graduate Student in Department of Pharmacology)
1980 

Alumni Award from Southern Illinois University
(Outstanding Graduating Senior in the Major of Science)
1993     Ministry of Education Outstanding Teacher Award
1990 – 2006

Chang Gung University Outstanding Teacher
(top 5%; ranked 1st  in several years;  student evaluation)
Patents
2006     Detecting Recurrence and High Stage Bladder Carcinoma.  
USA Patent No. 7011950 B2; Germany Patent No. 10326773; UK Patent No. GB2402212; Taiwan Patent No. I 242643
Being Applied

Nucleophosmin/B23-binding Peptide to Inhibit Tumor Growth and Regulate Transcriptional Activity of P53.
USA and Germany Patents
Being Applied Method of Identifying Cancer Biomarkers and Cancer Progression.
USA and Taiwan Patents
Management and Administrative Experience
2009

Headship
Department of Health Technology and Informatics
The Hong Kong Polytechnic University
2006 – 2008

Chairperson
Graduate Institute of Natural Products
Chang Gung University
2002 – 2005 Chairman of the User Committee of National Proteomics Core Facility
Taiwan
2001 – 2006 Dean (Vice-President in America / Hong Kong academic ranking system)
Office of Research and Development
Chang Gung University
2001 – 2006 Director of Chang Gung Genomics Research Center (includes Micro-array, Proteomics, Bioinformatics Cores)
Establishment of Genomics Center, Proteomics Center and Bioinformatics Center
1999 – 2005

Chairman of the New Medical Curriculum (PBL) Assessment Committee
Chang Gung University

1999 – 2000,
1993 – 1998,
2001 – 2006   

*Chairman (1999, 2000) and member (1993-1998, 2001-2006)
Biomedical Research Development & Grant Review Committee
(Governing the research development in Chang Gung University and all five Chang Gung Hospitals in Taiwan, ROC)
1998 – 2006 * Chairman of the Research Funding Review Committee
* Annual budget for research development and internal grants is 500 millions NTD.
1998 – 2006 Member of the Academic Promotion Committee of the University
Chang Gung University
1998 – 2001

Director
Office of Research Affairs (now becomes Office of Research and Development)
Chang Gung University

1992 – 1997,
2004 – 2008

Member of Advisory Committee
National Science Council (1992-1997), (2004-2006);
Physiology (2004-2008)
Taiwan
1992 – 1998

Member of Advisory Committee (Chinese Traditional Chinese Medicine & Pharmacology),
Ministry of Health
Taiwan
External Appointments (Honor)
2002 – 2004

Scientific Reviewer for Oncogene, Carcinogenesis, International Journal of Cancer, Cancer Letters, FEBS Letters.
Visiting Professorship in School of Nursing and Health Sciences
The Hong Kong Polytechnic University
2002 – 2004

Chairman of the Advisory Committee for the Biomedical Science Programme
The Hong Kong Polytechnic University
1990

Adjunct Professorship of The National Yang Ming University
Teaching-related Administration
1998 – 2000

Chairperson of Biomedical Science Graduate School Curriculum Committee
1992 – 2005

Medical students (4th year) adviser
1997 – 1999

Biomedical Science Graduate students (1st year) adviser
1994 – 1998

Member of Biomedical Science Graduate School Admission and Curriculum Committees
1994 – 2008

Member of Biomedical Science Graduate School Research Advancement Committee
Courses involved in Teaching and Curriculum Development
1. Advanced Biochemistry
2. Advanced Cell Biology
3. Cancer Biology
4. Advanced Biochemical Pharmacology
5. Graduate School Seminar Course Director
6. Cell nucleus, Cell Cycle Regulation
7. Regulation of Cell Growth, Differentiation and Apoptosis
8. Research Methodology
9. Research Ethics & Living
10. Pharmacology: Antibiotics, Anticancer drugs (Medical and Nursing Students)
 

Sixty students completed their studies under my supervision and graduated with M.S. and four with Ph.D.  
Two postdoctoral fellows and four of my Ph.D. graduates are faculty members in accredited Institutes in Taiwan.  
Currently I have one postdoctoral fellow, four Ph.D, three research associates and two college student working in my laboratory.
Main Research Areas
•

Cancer Biology, Nucleolus Research, Regulation of Cancer Cell Growth, Control of Cellular Response to Differentiation and Apoptosis
•

Applications of functional proteomics for exploring the pathogenesis and biological mechanisms of selected human cancers
•

Molecular genetic analysis of selected human cancers, identification and application of single nucleotide polymorphisms (SNPs), Development of novel molecular diagnostics and targets
Statement of Qualifications for Innovative Research

Throughout these years, we have been focusing our effort and making important progress on the study of the nucleolar protein nucleophosmin/B23 (NPM) and its biological role in cancer. In recent review on NPM and cancer by Grisendi et al (Nature Reviews 6, 493-505, 2006), fifteen (~10%) out of 146 manuscripts being sited are from our previous and current work on NPM.  It is evident that we have established a unique, novel system and strong background of NPM.  Most importantly, recent findings from our laboratory have identified a potential but mostly uncharacterized role of NPM in transcriptional regulation (EMBO Report, 8:394-400, 2007; Cellular Signaling 18:2041-2048, 2006; BBRC 335:826-831, 2005).  It prompts us to continue our study to advance our functional and mechanistic understanding of NPM’s transcriptional roles and further expand our view on the link between gene expression regulation (or mis-regulation) and tumorigenesis.  It is conceivable that we are able to establish an integrated, functional genomic-based system that will aid us in exploring an in-depth and global understanding of the roles of transcriptional regulators within a physiological and/or pathological context.
Representative Publications (Total Publications [journal articles, book chapters, monographs and conference papers])

Tumors are usually recognized by the fact that the cells have shown abnormal immortal growth.  Tumor cells differ from normal mortal cells in that they are no longer responsive to normal growth controlling mechanisms. Current chemotherapeutic drugs act for the most part by killing cancer cells directly while normal cells are also seriously damaged.  Researchers have begun trials of agents that act instead by changing the biological properties of cancer cells so that they lose one of the major characteristics, namely, the ability to divide continuously.  Our work on tumor differentiation and apoptosis aims to shift the balance back again, thereby removing the potential for uncontrolled growth from the tumor cells.

One important difference between cancer and normal cells is hyperactivity and pleomorphism of the nucleoli.  The nucleolus in cancer cells undergoes extreme variations in size, shape, fine structure, and cytochemical composition.  Little information is currently available on the nucleolar proteins, their characterizations and their roles in growth and cancer cells.  Many of our studies and others have indicated that nucleophosmin/B23 (NPM), one of the major nucleolar phosphoprotein, plays a role in increased nucleolar activity that is necessary for cancer cell proliferation.


For our research achievement, we have conducted pioneering work on nucleophosmin/B23-translocation. By using immunofluorescence techniques, we first observed that nucleophosmin/B23 translocated from nucleoli to nucleoplasm after treatment with anti-cancer drug actinomycin D and its analogs.  We then investigated the biochemistry of this phenomenon and found that the translocation of nucleophosmin/B23 is related to the inhibition of RNA synthesis and cell growth.  The significance of these findings is manifested by the subsequent development in my laboratory and other laboratories worldwhile that B23-translocation is an important method in determining and monitoring the effectiveness of cancer chemotherapy and will thus lead to valuble basic / clinical implication.


We have set up several cell growth conditions so as to study the biochemical roles of nucleophosmin/B23 in the regulation of cell growth and cell cycle.  We found that B23-translocation and subsequently the induction of apoptosis require ATP. Nucleophosmin/B23's being an ATP-binding protein and the ATP-binding site has already been determined in my laboratory.  These are important results and can lead to better understanding of the nucleophosmin/B23 translocation mechanism and its association with induction of apoptosis.  These results are considered as highly significant and a major contribution in this area.


In determining the biochemical roles of nucleophosmin/B23 in cell cycle, we have found that nucleophosmin/B23 being possibly involved in rRNA processing and transport, is highly active at G1 and G1/S phases as demonstrated by the dynamic, reversible changes of localization and oligomerization states of nucleophosmin/B23.  Furthermore, we have also shown that the mitotic phosphorylated form of nucleophosmin/B23 plays a role in maintaining mitotic chromosomes in their condensed state.


Furthermore, we found that nucleophosmin/B23 is transcriptionally down regulated during retinoic acid-induced cellular differentiation or sodium butyrate-induced apoptosis.  We have demonstrated that the tumor cells treated with nucleophosmin/B23 antisense oligomers contain markedly reduced levels of nucleophosmin/B23 mRNA are more susceptible and prone to be induced to differentiate or to die apoptotically.  The ability of nucleophosmin/B23 antisense oligonucleotide in the potentiation of induced cellular differentiation and apoptosis is particularly important and may lead to the use of antisense construct in cancer treatment.


Stable clones of HL-60 cells in which nucleophosmin/B23 is over-expressed or down regulated have been established in my laboratory.  Over-expression of nucleophosmin/B23 results in decreased susceptibility of the cells to the induction of apoptosis and inhibition of telomerase activity. On the other hand, down-regulation of nucleophosmin/B23 makes the cells more susceptible to induction of apoptosis or inhibition of telomerase activity.  Our results provide direct evidence that nucleophosmin/B23 plays a functional role in cellular response to apoptosis and immortalization.  Our effort and achievement of determining the regulatory role of nucleophosmin/B23 add critical and novel fundamental knowledge of the mechanism and forces guiding normal and cancer cell growth and to ultimately raise the possibility of making the immortal cancer cells "normal".

It has been known that IRF-1 (Interferon regulatory factor -1) plays a role in cell growth control and surveillance against cancer development. To better characterize the contribute of nucleophosmin/B23 in carcinogenesis, we have shown that having more nucleophosmin/B23 that is going to interact with IRF-1 is the basis for the nucleophosmin/B23 over-expressed cells being abnormal and resistant to induction of differentiation and apoptosis.  In UV irradiation experiments, our results show that nucleophosmin/B23 affects cellular response through PCNA and enhancement of DNA repair ability.  Nucleophosmin/B23 is associated with regulation of PCNA and DNA repair ability and plays an important role in cellular susceptibility to UV-induced growth inhibition and cell death.  Most recently, we found that UV-stimulation of nucleophosmin/B23 expression is an immediate-early gene response induced by damaged DNA.  We made a discovery of the novel gene and mechanism in cellular response to damaged DNA.

In conclusion, important information about the regulatory control in nucleolus for the tumor cell growth has been obtained.  We have made important progress in elucidating the biological roles of nucleophosmin/B23 in cellular response to cell growth control.   Throughout our studies these years, we have provided evidences, implicating that nucleophosmin/B23 gene has a critical functional role in growth control and its down-regulation could be associated with mortalization of tumor cells. The tumor cells treated with nucleophosmin/B23 antisense oligomers contain reduced levels of nucleophosmin/B23 mRNA are more susceptible to the induction of differentiation, apoptosis and inhibition of telomerase activity.

Important studies would be to elucidate how nucleophosmin/B23 is involved in the control of the response of cells to induction of cellular differentiation, apoptosis and inhibition of telomerase activity.  Down-regulation of nucleophosmin/B23 could be an important step in making the cancer cells back to "normal" or preventing the normal cells from becoming cancerous.  Nucleophosmin/B23 would be a potential target for therapeutic intervention in cancer.

Long-term objectives that may accrue from these studies are the development of novel and better understanding of the forces, cellular and molecular mechanisms guiding normal and cancer cell growth, differentiation and apoptosis.  It is hoped that this effort to gain some understanding of the regulation of cell cycle, cellular growth and mortality will eventually provide insights which will be useful for designing better strategies for overcoming tumorous cell growth.

Most Recent and Current Studies
1.
 In our previous work, transcription factor-transcription factor (TF-TF) binding array analysis of nuclear lysates was carried out to identify possible NPM-binding partners. Results from this assay confirmed previously identified interactions (YY1 and NF-κB) and also uncovered novel associated factors. AP-2α, EGR1, MEF-1, MEF-2, YY1 and NF- κB were specifically detected as candidate NPM-binding partners. Consistent with known attributes of NPM, many of the identified proteins appear to have roles in cell growth and development.
2.
 Based on the above study, we chose one of the candidate proteins, AP-2α, for further study. We found that the complex formation and transcriptional role of AP-2α-NPM is directly linked to the retinoic acid-mediated signaling and the associated gene expression. Notably, our data demonstrated for the first time that nucleophosmin/B23 (NPM) is directly involved in mediating the RA signaling-induced gene expression, acting as a negative co-regulator.
(EMBO Report: 394-400, 2007).
3
 To identify and analyze genomic regulatory regions with which NPM physically associates, we previously performed anti-NPM ChIP experiments coupled with microarray analysis. The oligonucleotide promoter array analysis was performed by NimbleGene Systems as part of a Chromatin Immunoprecipitation (ChIP) Array Service. Based on such study, we have recently identified numerous promoter regions specifically bound by NPM in HeLa cells. Although microarray data analysis is still underway, several putative target promoters have been identified in this screen thus far, including histone, hnRNP H3, ribosomal S6 and L12 genes.
4.
 The RA-induced differentiation of human leukemia HL-60 cells was accompanied by the decline in the protein levels of c-myc, NPM and its promoter activity.  There is a strong correlation of NPM and c-Myc expressions in cells under RA treatment.  CHIP assays showed that binding of c-Myc to the NPM promoter decreased in RA-treated cells.  NPM expression is targeted by c-Myc during RA-induced differentiation.
(Yung, FEBS Letters  578:211-216, 2004)
5.
 NPM over-expression was associated with bladder cancer recurrence (68.2%) and progression (88.9%) when adjusted for the effects of clinical stage. Patients with NPM mRNA over-expression were at significantly greater risk of disease recurrence and progression than those having low-expressions of NPM mRNA, suggesting a potential rationale for early definitive therapy in these patients.
(Tsui et al., Urology, 64: 839-844, 2004)
6.
 The Rev peptide that binds to NPM with the highest affinity exhibits the greatest cytotoxicity on cancer cells and inhibited tumor growth effectively in nude mice.  The anti-tumor activity of the NPM-binding peptide could be the consequences of increased protein expression of tumor suppressor p53 and its activity.  Peptides having high affinity of binding to molecular targets such as NPM represent a potentially useful approach to anti-cancer biotherapeutics.
(Chan et al., Biochemical & Biophysical Res. Commun. 333: 396-403, 2005.)
7.
 Ectopic over-expression of NPM causes a marked up-regulation in the amounts of YY1. PCNA PCNA expression and its promoter activity were attenulated by B23siRNA or YY1siRNA. The ChIP assay showed that positive regulation of PCNA is achieved by binding of YY1 to the initiation site of PCNA promoter. NPM plays an important role in the regulation of PCNA through YY1.
(Weng et al., Biochemical & Biophysical Res. Commun. 335: 826-831, 2005.)
8.
 NPM-siRNA treatment decreased E2F1-dependent transcriptional activity as well as the E2F1 promoter activity in U1 bladder cancer cells.  Furthermore, our co-immunoprecipitation experiments indicated the interactions of NPM with NF-κB and with pRB.  By TESS analysis, there are NFκB and E2F1 binding sites in E2F1 promoter. NF-κB and pRB could play a role in regulating E2F1.  Our results also showed that NPM regulated E2F1 through the interplay of NFκB and pRB.
(Lin et al., Cellular Signalling, 18: 2041-2048, 2006).
9.
 NPM was rapidly upregulated after UV irradiation as p53, PCNA and c-Jun.  NPM over-expressed cells had a greater capacity to repair UV-damaged reporter plasmid, indicating a higher nucleotide excision repair (NER) activity.  Both protein level and promoter activity of PCNA were higher in nucleophosmin/B23 over-expressed cells. NPM up-regulates PCNA, making cells resistant to UV-induced growth inhibition and cell killing.
(Wu et al., Carcinogenesis, 1:93-100, 2002)
10.
 UV stimulation of NPM expression is mediated through a novel UV-inducible pathway, and is an immediate-early gene response induced by damaged DNA.  Induction of immediate-early gene is an initial step in the regulation of cellular and genomic responses to external stimuli.  Our results thus provide important evidence for an involvement of NPM in the acute response of mammalian cells to environmental stress.
(Wu & Yung, J. Biological Chemistry, 277: 48234-48240, 2002)
11.
 Higher expression of Ras, c-Myc, and NPM as well as greater c-Myc transactivation and NPM promoter activities were detected in U1 cells of high malignancy as compared to U4 premalignant cells.  The increase of NPM promoter activity could be abrogated by MEK inhibitor and was associated with recruitment of c-Myc to the promoter. Constitutive expression of Ras dominant negative (Dn-Ras-U1) reduced the levels of Ras, NPM and p-ERK, and consequently abolished the serum-induced up-regulation of NPM promoter activity and c-Myc promoter recruitment.  Ras and c-Myc play important role in the up-regulation of NPM during proliferation of cells associated with high degree of malignancy, thus outlining a signaling cascade involving these factors in the cancer cells. 
(Molecular Pharmacology, 70:1443-1453, 2006)
12.
 To search for biomarkers critical for bladder carcinoma diagnosis and prognosis, secreted proteomes of highly malignant U1 and pre-malignant U4 cell lines were first analyzed. Proteins in the cultured media of the U1 and U4 cell-lines were systematically examined by SDS-PAGE combined with MALDI-TOF mass spectrometry. Among them, expression of pro-u-plasminogen activator (pro-u-PA) was confirmed by Western blot analysis and further evaluated. In analyzing urine samples from bladder cancer patients and normal subjects, we established a statistically significant relationship between the low level and absence of pro-u-PA in urine with high stages and grades of the tumor samples.  Constitutive expression of Ras dominant negative protein led to increased expression of pro-u-PA in cultured media, indicating the loss of pro-u-PA is associated with oncogenic transformation. Analysis of cancer-secreted proteomes can be a feasible, non-invasive and efficient strategy for searching potential bladder tumor biomarkers. Our work also has identified the loss of pro-u-PA in urine as potential marker of more advanced bladder carcinoma.
(Proteomics, 6: 4381-4389, 2006)
13.

NPM1 mutation evaluated in a population basis is valuable and realistic to reflect the patho-physiological relevance of cancer. In comparison of NPM1 cDNA of human bladder cancer with its consensus sequence, we have found that higher NPM1 sequence identity in a population is consistent with poor tumor differentiation, advanced tumor stage and likelihood of recurrence. These data imply that “probability” of NPM1 mutation is an indicator of status of malignancy.
(Genomics, 90:746-750, 2007)
14.
To investigate the efficacy of NPM protein level as a predictor of bladder carcinoma recurrence. Surgically resected tumors staged pTa to pT4 in bladder carcinoma were examined for nucleophosmin/B23 expression by immunohistochemistry. The study group consisted of 132 consecutive patients surgically treated at Chang Gung Memorial Hospital between December 1998 and November 1999. Mean follow-up was 72 months (range: 48–84 months). Recurrence-free probability was determined by Kaplan-Meier analysis. Using the Cox proportional hazards model, independent prognostic significance of NPM expression was assessed. Nuclear NPM staining was detected in 96% of advanced stage and poorly differentiated bladder tumors. High NPM levels were linked to advanced tumor stages, grades and recurrence (P<0.05). Cox multivariate analysis indicated that NPM expression correlated with time to bladder carcinoma recurrence (P=0.009) while not significantly different for bladder cancers of high tumor stages, nor was high histological tumor grades. Our study has identified NPM as a significant independent, favorable prognostic factor. High NPM staining is associated with tumor recurrence, which indicates poor prognosis for bladder carcinoma. NPM could be a useful molecular tumor marker for predicting bladder carcinoma recurrence.
(Acta Pharmacologica Sinica, 29: 364-370, 2008)
Referees
1.

Professor Pui Kwong CHAN

Department of Pharmacology
Baylor College of Medicine
One Baylor Plaza, Houston, Texas 77030 USA
Fax # (713) 798-3145
Email: pchan@bcm.tmc.edu

2.
 Professor Samuel H. H. CHAN

National Chair Professor of Neuroscience
Distinguished Chair Professor
Chang Gung Memorial Hospital
Center for Translational Research in Biomedical Sciences
123 Ta Pei Road, Kaohsiung County, 83301, Taiwan, R.O.C.
Tel: 886-7-731-7123  Ext 8099
Fax # 886-7-731-7123 Ext 8569
Email: shhchan@cgmh.org.tw
Publications (Total Publications [journal articles, book chapters, monographs and conference papers])

 

1.  Fukuyama, T.  and Yung, Y.M.   Total synthesis of ( )-methyl 3-(isocyano-  6-oxabicyclo 3.1.0. Hex-2-en-5-yl)-propenoate. Tetrahedron Letters 22: 3759-3760 (1982). SCI  IF: 2.357

2.  Yung, B. Y.M*., Busch,R.K., Busch,H., Mauger,A.B. and Chan, P.K.  Effects of actinomycin D analogs on nucleolar phosphoprotein B23 (37 Kd/5.1) Biochemical Pharmacology 34: 4059-4063 (1985). SCI  IF: 3.581

3.  Yung, B.Y.M*., Busch,H., and Chan,P.K.  Translocation of nucleolar phosphoprotein B23 (37 kd/pI 5.1) induced by selective inhibitors of ribosome synthesis.  Biochemica Et Biophysica Acta 826:167-173 (1985). SCI  IF: 1.782-9.581

4.  Yung, B.Y.M*., Busch,H., and Chan,P.K.  Effects of luzopeptins on protein B23 translocation and ribosomal -RNA synthesis.  Cancer Research 46: 922-925 (1986). SCI  IF: 7.656

5.  Chan,P.K., Chan,W.Y., Yung,B.Y.M., Cook,R.G., Aldrich,M.B., Ku,D., Goldknopf,I.C., and Busch,H.  Amino acid sequence of a specific antigenic peptide of protein B23.  The Journal of Biological Chemistry 261: 14335-14341 (1986). SCI  IF: 5.808

6.  Yung, B.Y.M*., and Chan,P.K.  Identification and characterization of a hexameric form of nucleolar phosphoprotein B23.  Biochemica Biophysica Acta 925:74-82 (1987). SCI  IF: 1.782-9.581

7.  Chan, P.K., Aldrich,M.B., and Yung, B.Y.M.  Nucleolar protein B23 translocation after doxorubicin treatment in Murine tumor cells.  Cancer Research 47:3798-3801 (1987). SCI  IF: 7.656

8.  Baker,T.A., Bertsch,L.L. Bramhill,D., Sekimizu,K., Wahle,E., Yung,B.Y.M., and Kornberg, A.  Enzymatic replication of plasmids from the Origin of the E. Coli chromosome.  In Cancer Cells pp. 19-24, Vol. 6 Eukaryotic DNA replication (T.J. Kelly and B. Stillman, eds.)  Cold Spring Harbor Laboratories, Cold Spring Harbour, N.Y. (1988). 

9.  Sekimizu,K., Yung,B.Y.M., and Kornberg, A.  The dnaA protein of E. coli:   Abundance, improved purification and membrane binding.  The Journal of Biological Chemistry 263: 7136-7140 (1988). SCI  IF: 5.808

10.    Kornberg, A., Baker,T.A., Bertsch,L.L. Bramhill,D., Sekimizu,K., Wahle,E., and Yung,B.Y.M.  Purified protein system for initiation of replication from the Origin of the E.coli chromosome.  DNA replication and mutagensis, edited by American Society for Microbiology, pp. 6-13, Chapter 1 (1988). 

11.    Yung,B.Y.M*., and Kornberg, A.   Membrane attachment activates dnaA protein, the initiation protein of replication in E.coli.  Proc. Natl. Acad. Sci. USA 85:7202-7205 (1988). SCI  IF: 9.643

12.    Yung,B.Y.M*., and Kornberg, A.  The dnaA initiator protein binds separate domains in the replicating Origin of E. coli. The Journal of Biological Chemistry 264: 6146-6150 (1989). SCI  IF: 5.808

13.    Chan, P.K., Yung,B.Y.M., and Aldrich,M.B.  Structural and functional studies of protein B23.  Progress in Nonhistone Protein Research, Vol III, CRC Press, Inc.  Chapther 2, pp. 11-38 (1989). 

14.    Yung,B.Y.M*., Crooke, E., and Kornberg, A.  Fate of the dnaA initiator protein in replication at the Origin of the E. coli chromosome in vitro.  The Journal of Biological Chemistry 265: 1282-1285 (1990). SCI  IF: 5.808

15.  Yung,B.Y.M., Bor, A.M.S., and Chan, P.K.  Short exposure to actinomycin D induces "reversible" translocation of protein B23 as well as "reversible" inhibition of cell growth and RNA synthesis in HeLa cells.  Cancer Research 50:5987-5991 (1990). SCI  IF: 7.656

16.  Yung,B.Y.M., Bor, A.M.S., and Yang, Y.H.  Immunolocalization of phosphoprotein B23 in proliferating and nonproliferating HeLa cells. International Journal of Cancer 46:272-275 (1990). SCI  IF: 4.7

17.  Yung,B.Y.M., Yang, Y.H., and Bor, A.M.S.  Nucleolar protein B23 translocation after deferoxamine treatment in a human leukemia cell line.      International Journal of Cancer   48: 779-784 (1991). SCI  IF: 4.7

18.  Yung,B.Y.M.,  Chang F.J., and Luo,K.J.  Dipyridamole enhancement of doxorubicin-induced translocation of nucleophosmin and inhibition of cell growth in HeLa cells.   International Journal of Cancer 49: 592-597 (1991). SCI  IF: 4.7

19.  Yung,B.Y.M.,  Chang F.J., and Bor,A.M.S.  Modulation of the reversibility of actinomycin D cytotoxicity in HeLa cells by verapamil.  Cancer Letters 60:221-227 (1991). SCI  IF: 3.277

20.  Yung,B.Y.M.,  and Bor,A.M.S.  Identification of high density lipoprotein in serum for determining doxorubicin anticancer efficacy in HeLa cells.  International Journal of Cancer 50: 951-957 (1992). SCI   IF: 4.7

21.  Hui,E.K.W., Yang,Y.H., and  Yung,B.Y.M.  Schedule-dependent sphinganine potentiation of retinoic acid-induced differentiation, cell growth inhibition and nucleophosmin translocation in a human leukemia cell line (HL-60).  Experimental hematology 20: 454-461 (1992). SCI  IF: 3.408

22.  Wei, L.L.L., Hui,E.K.W., Wei,J.S., and Yung,B.Y.M.  Alkaline phosphatase activity during differentiation of human promyelocytic leukemia cell line, HL-60.  Biochemical & Biophysical Res Communications 182: 487-494 (1992). SCI  IF: 2.855

23.  Yung,B.Y.M., Hui,E.K.W., and Chan,P.K.  Protein B23 (M.W./PI=37kD/5.1) is the only major protein extracted from HeLa nucleoli with 3 M urea.  Life Sciences 51: 915-920 (1992). SCI  IF: 2.389

24.  Yung,B.Y.M., Luo,K.J. and Hui,E.K.W.  Interaction of antileukemia agents adriamycin and daunomycin with sphinganine on the differentiation of human leukemia cell line (HL-60).  Cancer Research 52:3593-3597 (1992). SCI  IF: 7.656

25.  Hui,E.K.W., and Yung,B.Y.M.  Protein kinase C activity during sphinganine potentiation of retinoic acid-induced differentiation in a human leukemia cell line (HL-60).  Life Sciences 51:415-422 (1992). SCI  IF: 2.389

26.    Yung,B.Y.M., Chang F.J., Bor,A.M.S. and Lee,D.S.T.  Schedule- dependent effects of two consecutive divided low doses of actinomycin D on translocation of protein B23, inhibition of cell growth and RNA synthesis in HeLa cells.  International Journal of Cancer 52: 317-322  (1992). SCI  IF: 4.7

27.    Bor,A.M.S., Chang F.J., and Yung,B.Y.M.  Phosphoprotein B23 translocation and modulation of actinomycin D and doxorubicin cytotoxicity by dipyridamole in HeLa cells.    International Journal of Cancer 52: 658-663 (1992). SCI  IF: 4.7

28.    Hui,E.K.W., and Yung,B.Y.M.  Cell cycle phase-dependent effect of retinoic acid on the induction of granulocytic differentiation in HL-60 promyelocytic leukemia cells: Evidence for sphinganine potentiation of retinoic acid-induced differentiation.  FEBS Letters 318: 193-199 (1993). SCI  IF: 3.372

29.    Wei, L.L.L., Hui,E.K.W., Wei,J.S., Tzeng, W.F., and Yung,B.Y.M.  Alkaline phosphatase activity during differentiation of human promyelocytic leukemia cell line, HL-60.  Life Sciences 52: 2035-2043 (1993). SCI   IF: 2.389

30.    Yung,B.Y.M. and Hui,E.K.W.  Differential regulation of protein kinase C isoenzymes during sphinganine potentiation of retinoic acid-induced granulocytic differentiation in human leukemia HL-60 cells. Biochemical & Biophysical Res Communications 196: 1390-1400  (1993) SCI   IF: 2.855

31.    Wu, M.H., and Yung,B.Y.M.  Cell cycle phase-dependent cytotoxicity of actinomycin D in HeLa cells.  European Journal of Pharmacology 270:203-212 (1994). SCI  IF: 2.522

32.    Yung,B.Y.M., Hsiao,T.F., Wei,L.L.L., and Hui,E.K.W.  Sphinganine potentiation of dimethyl sulfoxide-induced granulocytic differentiation, increase of alkaline phosphatase activity and decrease of protein kinase C activity in a human leukemia cell line (HL-60).  Biochemical & Biophysical Res. Communications 199: 888-896 (1994). SCI  IF: 2.855

33.    Yung,B.Y.M.  Sphinganine potentiation of cellular differentiation induced by various anti-leukemia drugs in human leukemia cell line HL-60.  Naunyn-Schmiedeberg's Archives of Pharmacology 350: 575-581    (1994). SCI  IF: 2.779

34.    Wu, M.H., Lam, C.Y.,and Yung,B.Y.M.  Translocation of nucleophosmin / B23 from nucleoli to nucleopasm requires ATP.  The Biochemical Journal    305: 987-992 (1995). SCI  IF: 4.1

35.    Yung,B.Y.M. and Hui, E.K.W.  Differential cellular distribution of retinoic acid during staurosporine potentiation of retinoic acid-induced granulocytic differentiation in human leukemia HL-60 cells.  Journal of Biomedical Science 2: 154-159 (1995). SCI  IF: 2.322

36.    Wei, L. and Yung, B.Y.M.  Effects of okadaic acid and vanadate on TPA-induced monocytic differentiation in human promyelocytic leukemia cell line HL-60.  Cancer Letters 90: 199-205 (1995). SCI  IF: 3.277

37.    Kuo, C.L., Chou, C. C., and Benjamin Y.M. Yung.  Berberine complexes with DNA in the berberine-induced apoptosis in Human leukemic HL-60 cells.  Cancer Letters 93: 193-200 (1995). SCI  IF: 3.277

38.    Chou, C. C., Lam, C.Y., and Benjamin Y.M. Yung.  Intracellular ATP is required for actinomycin D-induced apoptoic cell death in HeLa cells.  Cancer Letters 96: 181-187 (1995). SCI  IF: 3.277

39.    Chou, Y. H., and Benjamin Y.M. Yung.  Cell cycle phase-dependent changes in localization and oligomerization states of nucleophosmin/B23.  Biochemical & Biophysical Research Communications 217: 313-325 (1995). SCI  IF: 2.855

40.    Lu, Y.Y., Lam, C.Y., and Benjamin Yat Ming Yung.  Decreased accumulation and dephosphorylation of the mitosis-specific form Nucleophosmin/B23 in staurosporine-induced chromosome decondensation.  The Biochemical Journal 317: 321-327 (1996). SCI  IF: 4.1

41.    Chang, S. T., and Benjamin Yat Ming Yung.  Potentiation of sodium butyrate-induced apoptosis by vanadate in human promyelocytic leukemia cell line HL-60.  Biochemical & Biophysical Research Communications 221: 594-601, (1996). SCI  IF: 2.855

42.    Yang, I, W., Chou, C. C., and Benjamin Yat Ming Yung.  Dose dependent effects of berberine on cell cycle pause and apoptosis in Balb/c 3T3 cells. Naunyn-Schmiedeberg's Archives of Pharmacology 354:102-108 (1996). SCI  IF: 2.779

43.    Chou, C. C., and Benjamin Yat Ming Yung.   Antiapoptotic effect of Ras in the apoptosis induced by serum deprivation and exposure to actinomycin D.  Naunyn-Schmiedeberg's Archives of Pharmacology 355: 177-182 (1997). SCI  IF: 2.779

44.    Chang, J. H., Lin, J. Y., Wu, M. H., and Benjamin Yat Ming Yung.  Evidence for nucleophosmin/B23's capabality of binding ATP.  The Biochemical Journal 329: 539-544 (1998) SCI   IF: 4.1

45.  Hsu, Z. Y., and Yung, B.Y.M.  Down-regulation of nucleophosmin/B23 during retinoic acid-induced differentiation of human promyeloicytic leukemia HL-60 cells.  Oncogene   16:915-924 (1998) SCI  IF: 6.872

46.  Liu, W.H. and Yung, B.Y.M.  Mortalization of human promyelocytic leukemia HL-60 cells to be more susceptible to sodium butyrate-induced apoptosis and inhibition of telomerase activity by down-regulation of nucleophosmin/B23.  Oncogene 17:3055-3064 (1998) SCI  IF: 6.872

47.    Wu, H. L., Hsu, C. Y., Liu, W.H. and Benjamin Yat Ming Yung.  Berberine-induced apoptosis of human leukemia HL-60 cells is associated with down-regulation of nucleophosmin/B23 and telomerase activity.  International  Journal of Cancer 81: 923-929 (1999) SCI  IF: 4.7

48.    Jiang, P.S. and Benjamin Yat Ming Yung.  Down-regulation of nucleophosmin/B23 mRNA delays the entry of cells into mitosis.  Biochemical & Biophysical Research Communications 257: 865-870 (1999). SCI  IF: 2.855

49.    Liu, H. T. and Benjamin Y. M. Yung.  In Vivo Interaction of Nucleophosmin / B23 and Protein C23 during Cell Cycle Progression in HeLa Cells.  Cancer Letters 144: 45-54   (1999). SCI  IF: 3.277

50.    Liu, W. H., Hsu C. Y., and Benjamin Yat Ming Yung.  Nucleophosmin/B23 regulates the susceptibility of human leukemia HL-60 cells to sodium butyrate-induced apoptosis and inhibition of telomerase activity.  International Journal of Cancer 83: 765-771 (1999). SCI  IF: 4.7

51.    You, B. J., Huang, I. J.,   Liu, W.H., Hung, Y.B., Chang, J. H., and Benjamin Y. M. Yung.  Decrease of nucleophosmin/B23 mRNA and telomerase activity during indomethacin-induced apoptosis of gastric KATO III cancer cells. Naunyn-Schmiedeberg's Archives of Pharmacology.  360: 683-690    (1999). SCI  IF: 2.779

52.    Jiang, P. S., Chang, J. H. and Benjamin Y. M. Yung.  Different kinases phosphorylate nucleophosmin/B23 at different sites during G2 and M phases of cell cycle.  Cancer Letters 153: 151-160 (2000). SCI  IF: 3.277

53.    Hsu, C. Y., and Benjamin Y. M. Yung Over-expression of nucleophosmin/B23 decreases the susceptibility of human leukemia HL-60 cells to retinoic acid-induced differentiation and apoptosis. International Journal of Cancer   88: 392-400 (2000). SCI  IF: 4.7

54.    Chou, C. C., and Benjamin Yat Ming Yung.  Increased stability of nucleophosmin/B23 in antiapoptotic effect of Ras during serum deprivation.  Molecular Pharmacology 59: 38-45 (2001). SCI  IF: 4.469

55.    Huang, W. H., Benjamin Y. M. Yung., Syu, W.J., and Wu Lee Y. H.  The nucleolar phosphoprotein B23 interacts with hepatitis Delta antigens and modulates the hepatitis Delta virus RNA replication.  The J. Biological Chemistry 276: 25166-25175 (2001). SCI  IF: 5.808

56.    Wu, M. H., Chang, J. H., and Benjamin Y. M. Yung.   Involvement of nucleophosmin/B23 in the response of HeLa cells to UV irradiation. International Journal of Cancer 97: 297-305 (2002). SCI  IF: 4.7

57.    Wu, M. H., Chang, J. H., and Benjamin Y. M. Yung.  Resistance to UV-induced cell-killing in nucleophosmin/B23 over-expressed NIH-3T3 fibroblasts: enhancement of DNA repair and up-regulation of PCNA in association with nucleophosmin/B23 over-expression. Carcinogenesis 1:93-100, 2002. SCI     IF: 5.366

58.    Wu, M. H., and Benjamin Y. M. Yung.  UV stimulation of nucleophosmin/B23 expression is an immediate-early gene response induced by damaged DNA. The J. Biological Chemistry   277: 48234-48240, 2002 SCI     IF: 5.808

59.    Hsu, C. Y., and Benjamin Y. M. Yung.  Involvement of nucleophosmin/B23 in TPA-induced megakaryotic differentiation of K562 cells.  British J. of Cancer 89: 1320-1326, 2003. SCI     IF: 4.459

60.    Tsui, K. H.  Cheng, A. J. Chang, P.L. Pan, T.L. and Benjamin Y. M. Yung.  Association of nucleophosmin/B23 mRNA expression with clinical outcome in patients with bladder carcinoma.  Urology 64: 839-844, 2004. SCI  IF: 2.13

61.    Benjamin Y. M. Yung.  C-myc-mediated expression of nucleophosmin/B23 decreases during retinoic acid-induced differentiation of human leukemia HL-60 cells.  FEBS Letters 578:211-216, 2005. SCI  IF: 3.372

62.    Chan, H. J., Weng, J. J, and Benjamin Y. M. Yung.  Nucleophosmin/B23-binding peptide inhibits tumor growth and up-regulates transcriptional activity of p53.  Biochemical & Biophysical Research Communications 333: 396-403 (2005). SCI  IF: 2.855

63.    Weng J.J. and Benjamin Y. M. Yung.  Nucleophosmin/B23 regulates PCNA promoter through YY1.  Biochemical & Biophysical Research Communications   335: 826-831 (2005). SCI  IF: 2.855

64.    Chang J.T.  Wang H.M. Chang K.W. Chen W.H. Wen M.C. Hsu Y.M. Benjamin Yat Ming Yung, Chen I.H. Liao C.T. Hsieh L.L. and Cheng A.J. identification of differentially expressed genes in oral squamous cell carcinoma (OSCC): Over-expression of NPM, CDK1 and NDRG1 and underexpression of CHES1.  Int. J. Cancer 114: 942-949 (2005). SCI  IF: 4.7

65.    Yeh C. W., Huang S.S., Lee R.P., & Benjamin Yat-Ming Yung.  Ras-dependent recruitment of c-myc for transcriptional activation of nucleophosmin/B23 in highly malignant U1 bladder cancer cells.   Molecular Pharmacology 2006; 70:1443-1453. SCI  IF: 4.469

66.    Chiao-Yun Lin,, Ke-Hung Tsui, Chih-Chia Yu, Chun-Wei Yeh, Phei-Lang Chang, Benjamin Yat-Ming Yung. Searching cell secreted proteomes for potential urinary bladder tumor markers.  Proteomics 2006; 6:4381-4389. SCI  IF: 5.735

67.    Chiao Yun Lin, Yu Chun Liang and Benjamin Yat-Ming Yung.  Nucleophosmin/B23 regulates transcriptional activation of E2F1 via modulating the promoter binding of NF-κB, E2F1 and pRB. Cellular Signalling 2006;18:2041-2048 SCI  IF: 4.887

68.    Chen C. L. Sung J. Cohen M. Chowdhury W.H. Sachs M.D. Li Y. Lakshmanan Y. Benjamin Yat Ming Yung, Lupoid S.E. and Rodriguez R. Valproic acid inhibits invasiveness in bladder cancer but not in prostate cancer cells. J. Pharmacology & Experimental Therapeutics  319: 533-542 (2006) SCI  IF: 3.956

69.    Hsuan Liu, Bertrand Chin-Ming Tan, Kai-Hung Tseng, Ching Ping Chuang, Chun-Wei Yeh, Kwang-Den Chen, Sheng-Chung Lee and Benjamin Yat-Ming Yung.  Nucleophosmin acts as a novel AP2α-binding transcriptional corepressor during cell differentiation.  EMBO Reports 8: 394-400, 2007. SCI  IF: 8.175

70.    Chien-Lun Chen, Ke-Hung Tsui, Phei-Lang Chang, and Benjamin Yat-Ming Yung. Can probability of genetic mutation be an indicator of clinical relevance?  Genomics, 90:746-750, 2007 SCI  IF: 3.588

71.    Ke-Hung Tsui, Horng-Heng Juang, Tsong-Hai Lee, Phei-Lang Chang, Chien-Lun Chen and Benjamin Yat-Ming Yung. Association of nucleophosmin/B23 with bladder cancer recurrence based immunohistochemical assessment in clinical samples.  Acta Pharmacologica Sinica, 29: 364-370, 2008. 

72.    Ke-Hung Tsui, Petrus Tang, Chiao-Yun Lin, Phei-Lang Chang, Chih-Hao Chang, Ya Ming Chiu AND Benjamin Yat-Ming Yung.  Loss of bikunin in urine as useful marker of bladder carcinoma.  Journal of Urology (In Press, 2010) 

 

* Being first author; my major work under the supervision and guidance of Professor P.K.Chan, Harris Busch or Arthur Kornberg during my graduate studies and postdoctoral training.

 

Benjamin Yat Ming Yung, (underlined), being corresponding author, work of my graduate students or research associates under my supervision and guidance.