A complete list of our published work can be found at Rana Lab Publications.

Selected Publications

A few examples of our team’s pioneering work and publications are highlighted below. 

RNAi, fundamental rules for RNA chemical modification, and catalytic function of ribonucleoprotein complexes that are required for gene silencing in human cells

RNAi in human cells: basic structural and functional features of small interfering RNA. Molecular Cell, 2002, 549.

siRNA function in RNAi: a chemical modification analysis. RNA, 2003, 1034.

Target accessibility dictates the potency of human RISC. Nature Struct Mol Biol, 2005, 469.

Illuminating the silence: understanding the structure and function of small RNAs. Nature Rev Mol Cell Biol, 2007, 23.

Lipid nanoparticle strategies to deliver RNA, genes, and mRNA vaccines

Design and creation of new nanomaterials for therapeutic RNAi. ACS Chem Biol, 2007, 237.

In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs). ACS Med Chem Lett, 2013, 720.

Design and assembly of new nonviral RNAi delivery agents by microwave-assisted quaternization (MAQ) of tertiary amines. Bioconjug Chem 2010, 1581.

Silencing microRNA by interfering nanoparticles in mice. Nucleic Acids Res 2011, e38.

RNA targeting small molecule drugs

We conceived and created novel technologies for on-bead small molecule synthesis with unique ID tags, screening, and identification of ligands to target RNA, inhibit RNA-protein interactions and to modulate RNA functions. Further studies of both structure-based drug design and structure-activity relationships (SAR) to develop novel compounds to treat viral infections and restore immune functions.

Inhibition of gene expression in human cells through small molecule-RNA interactions. Proc Natl Acad Sci USA, 1999, 12997.

HIV-1 TAR RNA Recognition by an Unnatural Biopolymer. JACS, 1997, 6444. 

Discovery of a small molecule Tat-trans-activation-responsive RNA antagonist that potently inhibits human immunodeficiency virus-1 replication. J Biol Chem, 2003, 39092.

Small-molecule inhibition of HIV-1 Vif. Nature Biotechnol, 2008, 1187.

Mechanism of microRNA function and RNA phase separation

Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54. PLoS Biology, 2006, e210

This work identified that RNA-induced silencing complexes (RISC) programmed with micro RNAs in human cells localizes to cytoplasmic mRNA processing bodies (P-bodies) via interactions with RCK/p54, a DEAD box helicase, which is a general repressor of translation. Cited in Textbooks (Nature of Biology, 3rd Edition 2006, and 5thEdition 2017).

Therapeutic targeting of microRNAs: current status and future challenges. Nature Rev Drug Discov, 2014, 622-638.

RNA phase separation and human retroviral host restriction factors

Analysis of HIV-1 viral infectivity factor-mediated proteasome-dependent depletion of APOBEC3G: correlating function and subcellular localization. J Biol Chem, 2005, 8387.

Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodies. PLoS Pathogens 2006, e41.

Cellular microRNA and P bodies modulate host-HIV-1 interactions. Molecular Cell, 2009, 696.

Reprogramming and differentiation of human induced pluripotent stem cells

Our laboratory has deciphered the role of small and large non-coding RNAs in stem cell pluripotency and differentiation. These studies led to the development of commercially available technologies to reprogram iPS cells and expand stem cell differentiation methods. 

RNA-mediated regulation of iPS cell generation. EMBO J, 2011, 823.

microRNAs modulate iPS cell generation. RNA, 2011, 1451.

Given the broad applications of small RNAs to reprogram iPS cells, this work was covered by several journals, including Cell Stem Cell, and media outlets and cited such as “small RNAs loom large during reprogramming” and “micro RNA cocktail helps turn skin cells into stem cell”. 

A kinase inhibitor screen identifies small-molecule enhancers of reprogramming and iPS cell generation. Nature Commun, 2012, 1085.

An evolutionarily conserved long noncoding RNA TUNA controls pluripotency and neural lineage commitment. Mol Cell, 2014, 1005.

This work identified a conserved lincRNA, delineated its molecular mechanism and Huntington’s disease relevance. 

Role of RNA methylation in immunity, virology, and cancer foundational to virology and immunity epitranscriptomics

Dynamics of the human and viral m(6)A RNA methylomes during HIV-1 infection of T cells. Nature Microbiol, 2016, 16011.

Dynamics of Human and Viral RNA Methylation during Zika Virus Infection. Cell Host Microbe 2016, 666.

METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection. Cell Rep, 2021, 109091.

HIV reprograms host m(6)Am RNA methylome by viral Vpr protein-mediated degradation of PCIF1. Nature Commun, 2021, 5543.

PCIF1-mediated deposition of 5′-cap N(6),2′-O-dimethyladenosine in ACE2 and TMPRSS2 mRNA regulates susceptibility to SARS-CoV-2 infection. Proc Natl Acad Sci USA, 2023, e2210361120

ALKBH5 regulates anti-PD-1 therapy response by modulating lactate and suppressive immune cell accumulation in tumor microenvironment. Proc Natl Acad Sci USA, 2020, 20159.

This study found that when an RNA-editing enzyme ALKBH5 is inhibited during cancer immunotherapy, metabolites such as lactate in the tumor microenvironment is changed in such a way that fewer immune-suppressing Treg and MDSCs cells accumulate, making the treatment more effective at enhancing the outcomes of immunotherapy and prolonging survival. 

Role of PCIF1-mediated 5′-cap N6-methyladeonsine mRNA methylation in colorectal cancer and anti-PD-1 immunotherapy. EMBO J, 2023, e111673

Human Organoid Models to study disease and develop new therapies

Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3. Cell Stem Cell, 2016, 258.

Due to the discovery of a new mechanism using human cerebral organoids, this work was covered by multiple local, National and International Media outlets including Nature, Science, NY times, Newsweek, NBC, BBC, etc. 

Revealing Tissue-Specific SARS-CoV-2 Infection and Host Responses using Human Stem Cell-Derived Lung and Cerebral Organoids. Stem Cell Reports, 2021, 437.

Small molecules targeting viral proteins, RNA methylation, and cell signaling pathways to develop new antivirals and anticancer drugs

Small-molecule inhibition of HIV-1 Vif. Nature Biotechnol, 2008, 1187.

Discovery of HIV-1 protease inhibitors with picomolar affinities incorporating N-aryl-oxazolidinone-5-carboxamides as novel P2 ligands. J Med Chem, 2006, 7342.

1,2,3-Triazoles as Amide Bioisosteres: Discovery of a New Class of Potent HIV-1 Vif Antagonists. J Med Chem, 2016, 7677. 

Small-molecule PTPN2 Inhibitors Sensitize Resistant Melanoma to Anti-PD-1 Immunotherapy. AACR Cancer Res Commun, 2023, 119.

Discovery and Mechanism of SARS-CoV-2 Main Protease Inhibitors. J Med Chem, 2022, 2866.

Rational Design and Optimization of m(6)A-RNA Demethylase FTO Inhibitors as Anticancer Agents. J Med Chem, 2022, 10920.

m(6)A-RNA Demethylase FTO Inhibitors Impair Self-Renewal in Glioblastoma Stem Cells. ACS Chem Biol, 2021, 324.