Laboratory of Molecular Microbiology

Program Description

Analyses of cellular factors that contribute to the post-transcriptional expression of HIV-1 RNAs; see Yedavalli et al. Retrovirology. 2011;8:61; Yedavalli and Jeang, PNAS, 2010;107:14787-92.

Our research focuses on studying host factors that influence the pathogenesis of human retroviruses HIV-1 and HTLV-I.

It covers three broad areas:

1. Investigation of host protein factors that regulate HIV-1 expression and HTLV-1 transformation of human cells
2. Study of non-coding RNAs and their functional implications on retroviral replication
3. Development of knock-out mouse models to investigate in vivo host protein functions.

Our studies on Lmna-/- Sun1-/- double knockout mice provided insights on pathological cellular and animal aging. Pathological aging contributes to oncogenesis as well as AIDS pathogenesis. (See Chen et al., Cell 2012;149:565-77)

Recent data

Some notable recent scientific findings from our research program include

1. The discovery of a deubiquitinase pathway for selective inflammatory activation of NF-kB
2. New insights into RNA modification and RNA-binding factors that affect HIV-1 post-transcriptional gene expression
3. Successful genome-wide characterization of 252 human host cell factors in Jurkat T cells that are contributory to HIV-1 replication
4. Evidence that abnormal protein accumulation in human Golgi bodies influences cellular aging in a mouse gene knock-out model
5. Characterization of several oncogenic microRNAs and their contributions to HTLV-1 oncogenesis

Schematic of genomewide RNAi screening that revealed 252 human Jurkat T-cells genes that contribute to HIV-1 replication. (See Yeung et al., J Biol Chem, 2009;284:19463-73).

Additional scientific findings

• OncomiRs are involved in the transformation of T cell by HTLV-1 Tax
• Inner nuclear membrane protein Sun1 contributes 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
• A genome-wide short hairpin RNA (shRNA) screening of Jurkat T cells performed for over 250 human proteins that contribute to productive HIV-1 replication
• RNA helicase DDX3 regulates Rev-dependent post-transcriptional HIV-1 RNA expression
• The characterization of microRNA profile changes in HIV type 1 (HIV-1) seropositive individuals
• The cloning and elucidation of mitotic spindle assembly checkpoint protein, MAD1

back to top

Biography

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 the National Cancer Institute and joined the Laboratory of Molecular Microbiology (LMM) in 1987.

Memberships

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

Editorial Boards

• Nucleic Acids Therapeutics
• Cancer Research
• Retrovirology
• Journal of Virology
• Journal of Biological Chemistry
• Cell and Bioscience
• Antioxidants & Redox Signaling
• Current Drug Targets-Infectious Disorders
• BMC Biology
• BMC Medicine
• Current Topics in Virology
• Frontiers in Bioscience

back to top

Research Group

Group back row, left to right: Laurent Houzet, Gustavo Brito, Zak Klase, Yan Li, Venkat Yedavalli, Xiang Liu
Front row, left to right: Sai-Wen Tang, Chia-Yen Chen, Linda Zane, Kuan-Teh Jeang
Not pictured: Quan Zhang

back to top

Selected Publications

Majone F, Jeang KT. Unstabilized DNA breaks in HTLV-1 Tax expressing cells correlate with functional targeting of Ku80, not PKcs, XRCC4, or H2AX. Cell Biosci. 2012 Apr 27;2(1):15.

Chen CY, Chi YH, Mutalif RA, Starost MF, Myers TG, Anderson SA, Stewart CL, Jeang KT. Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies. Cell. 2012 Apr 27;149(3):565-77.

Yedavalli VS, Jeang KT. Matrin 3 is a co-factor for HIV-1 Rev in regulating post-transcriptional viral gene expression. Retrovirology. 2011 Jul 20;8:61.

Yasunaga J, Lin FC, Lu X, Jeang KT. Ubiquitin-specific peptidase 20 targets TRAF6 and human T cell leukemia virus type 1 tax to negatively regulate NF-kappaB signaling. J Virol. 2011 Jul;85(13):6212-9.

Yedavalli VS, Jeang KT. Trimethylguanosine capping selectively promotes expression of Rev-dependent HIV-1 RNAs. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14787-92.

Watashi K, Yeung ML, Starost MF, Hosmane RS, Jeang KT. Identification of small molecules that suppress microRNA function and reverse tumorigenesis. J Biol Chem. 2010 Aug 6;285(32):24707-16.

Visit PubMed for a complete publication listing.

back to top