J. Shang

Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states

This study identifies a PPARγ ligand series that shifts the receptor's conformational ensemble between active and repressive states, revealing how subtle chemical changes influence its function.

Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19

The paper identifies a potent orally bioavailable SARS-CoV-2 PLpro inhibitor with in vitro and in vivo antiviral activity against SARS-CoV-2 and related coronaviruses.

Highly efficient in vivo mutagenesis method based on the endonuclease and exonuclease activity of Bacillus alcalophilus RecJ (BaRecJ)

This paper introduces a novel mutagenesis method using BaRecJ's endonuclease and exonuclease activities, showing broader mutation spectra and improved trait-associated gene identification in E. coli and S. cerevisiae.

Multifrequency control of Faraday wave bioassembly for constructing multiscale hPSC-derived neuronal networks

This paper introduces a multifrequency Faraday wave bioassembly technique to create multiscale neuronal networks from hPSCs, demonstrating spontaneous neuroelectrical activity.

Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats

This study shows that LNP-based vaccines induce time- and dose-dependent anti-PEG antibodies in rats, with immune memory and accelerated blood clearance upon re-injection.

Molecular basis of ligand-dependent Nurr1-RXRα activation

This study identifies a novel mechanism by which RXR ligands activate Nurr1-RXR transcriptional activity through disruption of the heterodimer interface.

A chemical molecule promotes Trop2+ biliary duct organoids differentiation into insulin-secreting cells

This paper shows a chemical molecule enhances the differentiation of biliary duct organoids into insulin-secreting cells, improving glucose sensitivity in diabetic mice.

The Development of a Novel Nanobody Therapeutic for SARS-CoV-2

This paper develops a potent, low-cost nanobody therapeutic, Nanosota-1C-Fc, that effectively blocks SARS-CoV-2 infection in vitro and in vivo with high affinity and stability.

Structural Mechanism Underlying Ligand Binding and Activation of PPARγ

This study reveals that PPARγ ligand binding involves a two-step induced fit mechanism, supported by NMR, SPR, and ITC analyses, with ligand entry through a surface pore and conformational changes leading to active helix 12 exposure.

Human Microbial Transplant Restores T Cell Cytotoxicity and Anti-Tumor Response to PD-L1 Blockade in Gnotobiotic Mice

The paper shows that human microbial transplants can restore T cell cytotoxicity and anti-tumor response to PD-L1 blockade in gnotobiotic mice by altering immune cell infiltration and gene expression.

CAR/Nr1i3 directs T cell adaptation to bile acids in the small intestine

This study identifies CAR/Nr1i3 as a regulator of T cell adaptation to bile acids in the small intestine, showing its role in detoxification and inflammation resolution.

Quantitative Structural Assessment of Graded Receptor Agonism

The paper quantifies how agonist structure affects PPARγ conformational changes, showing efficacy correlates with shifts toward active states detected by NMR.

Cooperative Cobinding of Synthetic and Natural Ligands to the Nuclear Receptor PPARγ

The paper shows synthetic and natural ligands can bind cooperatively to PPARγ, altering its structure and function through a 'ligand link' to the omega loop.

Structural basis of altered potency and efficacy displayed by a major in vivo metabolite of the anti-diabetic PPARγ drug pioglitazone

This study compares the structure and function of pioglitazone and its metabolite 1-hydroxypioglitazone bound to PPARγ, showing reduced potency and efficacy of the metabolite.

Defining a canonical ligand-binding pocket in the orphan nuclear receptor Nurr1

This study shows the Nurr1 ligand-binding domain has a dynamic, solvent-accessible pocket that can bind unsaturated fatty acids, challenging the notion that it lacks a canonical ligand-binding pocket.

A structural mechanism for directing inverse agonism of PPARγ

The paper shows how a phenyl-to-pyridyl substitution in PPARγ ligands converts an antagonist to an inverse agonist through a water-mediated hydrogen bond network involving Arg288.