Laboratory of Molecular Microbiology

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

Senior Investigator
Chief, Molecular Virology Section

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.

Additional scientific findings from our research program include the following:

• OncomiRs are involved in the transformation of T cell by HTLV-1 Tax.
• Inner nuclear membrane protein Sun1 contribute to reproductive gene expression.
• Peptidylproline cis-trans-isomerase Pin1 interacts with human T-cell leukemia virus type 1 tax and modulates its activation of NF-kB.
• HTLV-I Tax dimerization is required for optimal trans-activation.
• A genome-wide short hairpin RNA (shRNA) screening of Jurkat T-cells performs for over 250 human proteins that contribute to productive HIV-1 replication.
• Tax has an effect on cell cycle progression that impinges on the cellular roles of cyclin D-cdk and p110RB.
• We isolated a human suppressor of JNK1 activation by TNFa.
• We characterized microRNA profile changes in HIV type 1 (HIV-1) seropositive individuals.
• We cloned and elucidated 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

Group back row, left to right: Yan Li, Kuan-Teh Jeang, Junichiro Yasunaga, Koichi Watashi
Group front row, left to right: Chia-Yen Chen, Christina Bezon, Zachary Klase
Individuals, top to bottom: Man Lung Yeung, Venkat Yedavalli, Laurent Houzet

Selected Publications

(View list in PubMed.)

Yeung ML, Houzet L, Yedavalli VS, Jeang KT. A genome-wide short hairpin RNA screening of jurkat T cells for human proteins contributing to productive HIV-1 replication. J Biol Chem. 2009 Jul 17;284(29):19463-73.

Chi YH, Cheng LI, Myers T, Ward JM, Williams E, Su Q, Faucette L, Wang JY, Jeang KT. Requirement for Sun1 in the expression of meiotic reproductive genes and piRNA. Development. 2009 Mar;136(6):965-73.

Peloponese JM Jr, Yasunaga J, Kinjo T, Watashi K, Jeang KT. Peptidylproline cis-trans-isomerase Pin1 interacts with human T-cell leukemia virus type 1 tax and modulates its activation of NF-kappaB. J Virol. 2009 Apr;83(7):3238-48.

Houzet L, Yeung ML, de Lame V, Desai D, Smith SM, Jeang KT. MicroRNA profile changes in human immunodeficiency virus type 1 (HIV-1) seropositive individuals. Retrovirology. 2008 Dec 29;5:118.

Yeung ML, Yasunaga J, Bennasser Y, Dusetti N, Harris D, Ahmad N, Matsuoka M, Jeang KT. Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced  nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1. Cancer Res. 2008 Nov 1;68(21):8976-85.

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.

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