Research Topics
Genomes and Genes
| Tariq M RanaSummaryAffiliation: University of Massachusetts Medical School Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Specific and potent RNAi in the nucleus of human cellsG Brett Robb
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Nat Struct Mol Biol 12:133-7. 2005..These studies reveal new roles for the RNAi machinery in modulating post-transcriptional gene expression in the nucleus...
Discovery of HIV-1 protease inhibitors with picomolar affinities incorporating N-aryl-oxazolidinone-5-carboxamides as novel P2 ligandsAkbar Ali
Chemical Biology Program, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Med Chem 49:7342-56. 2006..8 pM), and even against the MDR variants it retains picomolar to low nanomolar K(i), which is highly comparable with the best FDA-approved protease inhibitors...
Design and creation of new nanomaterials for therapeutic RNAiHuricha Baigude
ACS Chem Biol 2:237-41. 2007..iNOP treatment was nontoxic and did not induce an immune response. Our results show that these iNOPs can silence disease-related endogenous genes in clinically acceptable and therapeutically affordable doses...
Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteresG S Kiran Kumar Reddy
Chemical Biology Program and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Med Chem 50:4316-28. 2007..Based on the crystal structures and knowledge of structure-activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies...
Illuminating the silence: understanding the structure and function of small RNAsTariq M Rana
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Nat Rev Mol Cell Biol 8:23-36. 2007..In particular, it has highlighted the assembly and function of the RNA-induced silencing complex (RISC), and has provided guidelines to efficiently silence genes for biological research and therapeutic applications of RNAi...
Structure-based design, synthesis, and structure-activity relationship studies of HIV-1 protease inhibitors incorporating phenyloxazolidinonesAkbar Ali
University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States
J Med Chem 53:7699-708. 2010..Further optimization of these compounds using structure-based design may lead to the development of novel protease inhibitors with improved activity against drug-resistant strains of HIV-1...
Identification of flavopiridol analogues that selectively inhibit positive transcription elongation factor (P-TEFb) and block HIV-1 replicationAkbar Ali
Chemical Biology Program, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605 USA
Chembiochem 10:2072-80. 2009..These compounds are valuable molecular probes for understanding P-TEFb-regulated cellular and HIV-1 gene transcription and provide potential anti-HIV-1 therapeutics...
Cellular microRNA and P bodies modulate host-HIV-1 interactionsRobin Nathans
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
Mol Cell 34:696-709. 2009..Thus we provide an example of a single host miRNA regulating HIV-1 production and infectivity. These studies highlight the significance of miRNAs and P bodies in modulating host cell interactions with HIV-1 and possibly other viruses...
Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54Chia Ying Chu
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
PLoS Biol 4:e210. 2006..These studies also suggest that translation suppression by miRISC does not require P-body structures, and location of miRISC to P-bodies is the consequence of translation repression...
Small-molecule inhibition of HIV-1 VifRobin Nathans
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Nat Biotechnol 26:1187-92. 2008..These results demonstrate that the HIV-1 Vif-A3G axis is a valid target for developing small molecule-based new therapies for HIV infection or for enhancing innate immunity against viruses...
Quantitative analysis of RNA-mediated protein-protein interactions in living cells by FRETYa Lin Chiu
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Chem Biol Drug Des 69:233-9. 2007....
Modulating HIV-1 replication by RNA interference directed against human transcription elongation factor SPT5Yueh Hsin Ping
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
Retrovirology 1:46. 2004....
Design and assembly of new nonviral RNAi delivery agents by microwave-assisted quaternization (MAQ) of tertiary aminesAnimesh Ghosh
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Bioconjug Chem 21:1581-7. 2010..This strategy can be employed to develop new classes of nonviral gene delivery agents under safe and fast reaction conditions...
Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodiesMichael J Wichroski
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
PLoS Pathog 2:e41. 2006..Taken together, the results of this study reveal a novel link between innate immunity against retroviruses and P-bodies suggesting that APOBEC3G and APOBEC3F could function in the context of P-bodies to restrict HIV-1 replication...
Evaluating the substrate-envelope hypothesis: structural analysis of novel HIV-1 protease inhibitors designed to be robust against drug resistanceMadhavi N L Nalam
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
J Virol 84:5368-78. 2010....
P-TEFb kinase complex phosphorylates histone H1 to regulate expression of cellular and HIV-1 genesSiobhan K O'Brien
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 285:29713-20. 2010..We identify histone H1 as a novel P-TEFb substrate, and our results suggest new roles for P-TEFb in both cellular and HIV-1 transcription...
Orientation and affinity of HIV-1 Tat fragments in Tat-TAR complex determined by fluorescence resonance energy transferHong Cao
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Bioconjug Chem 17:352-8. 2006..Our results suggest that the N- and C-termini of Tat (38-72) are close to each other when the peptide is folded and that the peptide does not go through a large structural change upon TAR binding...
Inhibition of human immunodeficiency virus type 1 replication by RNA interference directed against human transcription elongation factor P-TEFb (CDK9/CyclinT1)Ya Lin Chiu
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Virol 78:2517-29. 2004....
U30 of 7SK RNA forms a specific photo-cross-link with Hexim1 in the context of both a minimal RNA-binding site and a fully reconstituted 7SK/Hexim1/P-TEFb ribonucleoprotein complexFrancois Belanger
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605 2324, USA
J Mol Biol 386:1094-107. 2009..Our results demonstrate directly that the Hexim1 binding site is located in the 24-87 region of 7SK RNA and that the protein residues outside the basic domain of Hexim1 are involved in specific RNA interactions...
Design and synthesis of a novel peptidomimetic inhibitor of HIV-1 Tat-TAR interactions: squaryldiamide as a new potential bioisostere of unsubstituted guanidineChi-Wan Lee
Chemical Biology Program, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605-2324, USA
Bioorg Med Chem Lett 15:4243-6. 2005....
Dissecting RNA-interference pathway with small moleculesYa-Lin Chiu
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Chem Biol 12:643-8. 2005..ATPA-18 analogs will therefore provide a new class of small molecules for studying RNAi mechanisms in a variety of model organisms and deciphering in vivo genetic functions through reverse genetics...
Phosphorylation of histone H1 by P-TEFb is a necessary step in skeletal muscle differentiationSiobhan K O'Brien
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School Worcester, Worcester, Massachusetts, USA
J Cell Physiol 227:383-9. 2012..We determine that both P-TEFb activity and H1 phosphorylation are necessary for the full differentiation of C2C12 myoblasts into myotubes...
Target accessibility dictates the potency of human RISCKirk M Brown
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Nat Struct Mol Biol 12:469-70. 2005..Kinetic studies revealed that siRNA-programmed RISC(*) cleaved target RNA with higher efficiencies when target site access was increased. These results provide evidence that target site access is linked to RISC(*) catalysis...
Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cellsYa-Lin Chiu
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Chem Biol 11:1165-75. 2004..These results suggest that interactions with RISC dictate siRNA localization even when siRNA is conjugated to TAT(47-57) peptide...
RNA helicase A interacts with RISC in human cells and functions in RISC loadingG Brett Robb
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Mol Cell 26:523-37. 2007..Our results identify RHA as a RISC component and demonstrate that RHA functions in RISC as an siRNA-loading factor...
Discovery of a small molecule Tat-trans-activation-responsive RNA antagonist that potently inhibits human immunodeficiency virus-1 replicationSeongwoo Hwang
Chemical Biology Program, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605-2324, USA
J Biol Chem 278:39092-103. 2003..Our results also suggest a general strategy for discovering pharmacophores targeting RNA structures that are essential in progression of other infectious, inflammatory, and genetic diseases...
Synthesis and structure-activity relationship studies of HIV-1 virion infectivity factor (Vif) inhibitors that block viral replicationAkbar Ali
Chemical Biology Program, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
ChemMedChem 7:1217-29. 2012....
Small RNAs: regulators and guardians of the genomeChia Ying Chu
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Cell Physiol 213:412-9. 2007....
Evolutionary emergence of microRNAs in human embryonic stem cellsHong Cao
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
PLoS ONE 3:e2820. 2008..One could imagine that this burst of miRNA gene clusters at specific chromosomes was part of an evolutionary event during species divergence...
Potent RNAi by short RNA triggersChia Ying Chu
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
RNA 14:1714-9. 2008..These results suggest that RISC assembly and activation during RNAi does not necessarily require a 19-nt duplex siRNA and that 16-nt duplexes can be designed as more potent triggers to induce RNAi...
Silencing microRNA by interfering nanoparticles in miceJie Su
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Nucleic Acids Res 39:e38. 2011..Our results demonstrate that iNOPs can successfully deliver anti-miR to specifically target and silence miRNA in clinically acceptable and therapeutically affordable doses...
Design, microwave-assisted synthesis, and photophysical properties of small molecule organic antennas for luminescence resonance energy transferHong-Kee Lee
Program in Chemical Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA
J Comb Chem 7:279-84. 2005..Two of these analogues showed very favorable fluorescence profiles and have the potential to be used as small molecule organic antennas for LRET studies...
siRNA function in RNAi: a chemical modification analysisYa-Lin Chiu
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
RNA 9:1034-48. 2003..Collectively, this study defines the mechanisms of RNAi in human cells and provides new rules for designing effective and stable siRNAs for RNAi-mediated gene-silencing applications...
Solid-phase synthesis of alpha-(2-(benzylthio)-1,4-dihydro-6-methyl-4-p-tolylpyrimidine-5-carboxamido) acids: a new strategy to create diversity in heterocyclic scaffoldsLei Zhang
Program in Chemical Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA
J Comb Chem 6:457-9. 2004
Dynamics of nascent mRNA folding and RNA-protein interactions: an alternative TAR RNA structure is involved in the control of HIV-1 mRNA transcriptionSara N Richter
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605-2324, USA
Nucleic Acids Res 34:4278-92. 2006..Finally, our results provide a new experimental strategy for studying mRNA conformation changes during transcription that can be applied to investigate the folding and function of nascent RNA structures transcribed from other promoters...
Analysis of HIV-1 viral infectivity factor-mediated proteasome-dependent depletion of APOBEC3G: correlating function and subcellular localizationMichael J Wichroski
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 280:8387-96. 2005..Taken together, these results demonstrate that cytoplasmic Vif-APOBEC3G interactions are required but are not sufficient for Vif to modulate APOBEC3G and can be monitored by co-localization in vivo...
Tat stimulates cotranscriptional capping of HIV mRNAYa Lin Chiu
Chemical Biology Program, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Mol Cell 10:585-97. 2002..Our findings implicate capping in an elongation checkpoint critical to HIV gene expression...
Nanotubes functionalized with lipids and natural amino acid dendrimers: a new strategy to create nanomaterials for delivering systemic RNAiJoshua McCarroll
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Bioconjug Chem 21:56-63. 2010..This new technology not only can be used for systemic RNAi, but may also be used to deliver other drugs in vivo...
Discovery of nonsteroidal anti-inflammatory drug and anticancer drug enhancing reprogramming and induced pluripotent stem cell generationChao shun Yang
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Stem Cells 29:1528-36. 2011..This hypothesis-driven approach provides an alternative to shot-gun screening and accelerates understanding of molecular mechanisms underlying iPSC induction...
A new class of RNA-binding oligomers: peptoid amide and ester analoguesVenkitasamy Kesavan
Chemical Biology Program, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605-2324, USA
Bioconjug Chem 13:1171-5. 2002..These results show that we have identified a new class of unnatural oligomers for RNA targeting...
Mechanism of site-specific psoralen photoadducts formation in triplex DNA directed by psoralen-conjugated oligonucleotidesYueh-Hsin Ping
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Biochemistry 44:2501-9. 2005..Taken together, these studies provide new insight into the mechanism associated with the formation of psoralen photoadducts that are directed by psoTFO during triplex formation...
Therapeutic gene silencing delivered by a chemically modified small interfering RNA against mutant SOD1 slows amyotrophic lateral sclerosis progressionHongyan Wang
Department of Biochemistry and Molecular Pharmacology, Chemical Biology Program, Cell Biology, and Neuroscience Program, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
J Biol Chem 283:15845-52. 2008..These results bring RNA interference therapy one step closer to its clinical application for treatment of chronic, devastating, and fatal CNS disorders...
RNAi in human cells: basic structural and functional features of small interfering RNAYa-Lin Chiu
Chemical Biology Program, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
Mol Cell 10:549-61. 2002..These results suggest that RNA amplification by RNA-dependent RNA polymerase is not essential for RNAi in human cells...
Microwave-assisted parallel synthesis of a 4,6-diamino-2,2-dimethyl-1,2-dihydro-1-phenyl-s-triazine libraryHong-Kee Lee
Program in Chemical Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA
J Comb Chem 6:504-8. 2004..Isolated yields of all the compounds were comparable when the two methods were used...
The frameshift signal of HIV-1 involves a potential intramolecular triplex RNA structureJonathan D Dinman
Department of Cell Biology and Molecular Genetics, 2135 Microbiology Building, University of Maryland, College Park, MD 20742, USA
Proc Natl Acad Sci U S A 99:5331-6. 2002..We suggest that the potential intramolecular triplex structure is essential for viral propagation and viability, and that small molecules targeted to this RNA structure may possess antiretroviral activities...
HIV-1 protease inhibitors from inverse design in the substrate envelope exhibit subnanomolar binding to drug-resistant variantsMichael D Altman
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Am Chem Soc 130:6099-113. 2008....
Research Grants
- TARGETING HIV VIF PROTEINTARIQ RANA; Fiscal Year: 2003..These pharmacological probes of Vif function can provide important new insights into HIV biology. ..
