Kuan-Teh Jeang, M.D., Ph.D.

Senior Investigator
Chief, Molecular Virology Section

Dr. Jeang received his M.D. and Ph.D. from Johns Hopkins University School of Medicine in 1984. He performed his postdoctoral studies with the late George Khoury at NCI and joined the Laboratory of Molecular Microbiology (LMM) in 1987.

Description of Research Program

Screening of small molecule drugs that inhibit Tat-binding to TAR RNA; see Hwang, et al. J Biol Chem. 2003. 278, 39092-39103.

Our research focuses on basic and applied studies on human retroviruses HIV-1 and HTLV-I.

It covers three broad areas:

1. Basic research studying the regulated expression of HIV-1
2. Basic research on cellular transformation events as related to HTLV-I
3. Applied research towards developing HIV-1-based vectors, RNA interference against HIV-1, and identifying small antiviral molecules

Our laboratory also works on the HTLV-I Tax oncoprotein.

We have made numerous mutants which have contributed to the mapping of functional domains in Tax (see Van, et al., 2000).

Recent Data

Some notable recent scientific findings from our research program in include

1. The discovery of compounds that inhibit human RNA helicase DDX3 which is a cellular cofactor for HIV-1 post-transcriptional gene expression
2. The study of siRNAs and miRNAs that can regulate HIV-1 replication and HTLV-1 transformation of cells
3. The development of a microarray assay for measuring changes in cellular miRNA expression profiles
4. The study of check point dysfunction in HTLV-1 transformed cells
5. The characterization of centrosomal abnormalities caused by the HTLV-1 Tax oncoprotein
6. The identification of Akt as a signal transducer of Tax's transforming function

Infection of alveolar macrophages by an engineered HIV-1 virus expressing green fluorescent protein. Fluorescent images are shown in "false" colors; for additional details see Rich, et al., 2002.

1. The demonstration that the promoter activity of Tat functions at a step subsequent to TBP-recruitment
2. Evidence that intravirion delivery of Tat indicates a role for this protein at a pre-integration step
3. The finding that HIV-1 Tat modulates DNA-PK-mediated phosphorylation of Sp1
4. The identification of a novel human thioredoxin peroxidase that regulates IkB-a phosphorylation and NF-kB activation
5. The elucidation of HTLV-I Tax dimerization as being required for optimal trans-activation
6. The observation of an interaction between HTLV-I Tax and cytokeratin that results in changes in keratin-containing cytoskeletal networks
7. The clarification of an effect of Tax on cell cycle progression that impinges on the cellular roles of cyclin D-cdk and p110RB
8. The isolation of a human suppressor of JNK1 activation by TNFa
9. The generation of infectious HIV viral particles containing a therapeutic ribozyme
10. The efficient expression using an alphavirus replicon of a functional ribozyme targeted to HIV-1
11. The cloning and elucidation of a new mitotic spindle assembly checkpoint protein

Memberships

• American Society for Microbiology
• American Association for the Advancement of Science
• Society of Chinese Bioscientists in America
• American Society for Clinical Investigation

Editorial Boards

• Oligonucleotides
• Cancer Research
• Retrovirology
• Journal of Virology
• Journal of Biological Chemistry
• Archives of Biochemistry and Biophysic
• Antioxidants & Redox Signaling
• Current Drug Targets-Infectious Disorders
• Drug Design Reviews
• Current Topics in Virology
• Frontiers in Bioscience

Research Group Members

Yamina Bennasser (ybennasser@mail.nih.gov), Ya-Hui Chi (ychi@mail.nih.gov), Yan Li (yanli@mail.nih.gov), Jean-Marie Peloponese (jmpeloponese@niaid.nih.gov), Geeta Sahu (sahug@mail.nih.gov); Venkat Yedavalli (vyedavalli@mail.nih.gov), Man Lung Yeung (yeungm@mail.nih.gov), Takao Kinjo (kinjot@mail.nih.gov)

Selected Publications

(View list in PubMed.)

Iha H, Peloponese JM, Verstrepen L, Zapart G, Ikeda F, Smith CD, Starost MF, Yedavalli V, Heyninck K, Dikic I, Beyaert R, Jeang KT. Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-kappaB activation. EMBO J. 2008 Feb 20;27(4):629-41.

Lee JH, Yedavalli VR, Jeang KT. Activation of HIV-1 expression and replication by cGMP dependent protein kinase type 1-beta (PKG1beta). Retrovirology. 2007 Dec 13;4:91.

Gironella M, Seux M, Xie MJ, Cano C, Tomasini R, Gommeaux J, Garcia S, Nowak J, Yeung ML, Jeang KT, Chaix A, Fazli L, Motoo Y, Wang Q, Rocchi P, Russo A, Gleave M, Dagorn JC, Iovanna JL, Carrier A, Pébusque MJ, Dusetti NJ. Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci USA. 2007 Oct 9;104(41):16170-5.

Chi YH, Haller K, Peloponese JM Jr, Jeang KT. Histone acetyltransferase hALP and nuclear membrane protein hsSUN1 function in de-condensation of mitotic chromosomes. J Biol Chem. 2007 Sep 14;282(37):27447-58.

Matsuoka M, Jeang KT. Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation. Nat Rev Cancer. 2007 Apr;7(4):270-80.

Triboulet R, Mari B, Lin YL, Chable-Bessia C, Bennasser Y, Lebrigand K,Cardinaud B, Maurin T, Barbry P, Baillat V, Reynes J, Corbeau P, Jeang KT, Benkirane M. Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science. 2007 Mar 16;315(5818):1579-82.

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