Shen Zhang

Bio: Shen Zhang is an academic researcher from University of Virginia. The author has contributed to research in topics: Peroxynitrite & Reactive nitrogen species. The author has an hindex of 5, co-authored 12 publications receiving 112 citations. Previous affiliations of Shen Zhang include University of California, Riverside & Sichuan University.

A Sensitive Near-Infrared Fluorescent Sensor for Mitochondrial Hydrogen Sulfide

Abstract: Hydrogen sulfide (H2S) is an important gasotransmitter. Although a large number of fluorescent probes for cellular H2S have been reported, only a few can detect H2S in mitochondria, a cellular organelle connecting H2S with mitochondrial function and metabolic pathways. We hereby describe a novel near-infrared fluorescent probe, nimazide, by introducing sulfonyl azide to the core structure of a QSY-21 dark quencher. Nimazide responded quickly to H2S, resulting in robust fluorescence turn-off changes. This conversion displayed high specificity and fast kinetics. More impressively, we observed a robust fluorescence decrease in live cells loaded with mitochondrial nimazide in response to extracellular addition of nanomolar H2S, and successfully imaged biologically generated mitochondrial H2S in live mammalian cells. Nimazide is one of the most sensitive fluorescent probes for mitochondrial H2S.

A Genetically Encoded, Ratiometric Fluorescent Biosensor for Hydrogen Sulfide.

Abstract: As an important gasotransmitter, hydrogen sulfide (H2S) plays crucial roles in cell signaling. Incorporation of p-azidophenylalanine (pAzF) into fluorescent proteins (FPs) via genetic code expansio...

Genetically Encoded, Photostable Indicators to Image Dynamic Zn2+ Secretion of Pancreatic Islets.

Abstract: As an essential element for living organisms, zinc (Zn2+) exerts its biological functions both intracellularly and extracellularly. Previous studies have reported a number of genetically encoded Zn...

A general strategy to red-shift green fluorescent protein-based biosensors.

Abstract: Compared with green fluorescent protein-based biosensors, red fluorescent protein (RFP)-based biosensors are inherently advantageous because of reduced phototoxicity, decreased autofluorescence and enhanced tissue penetration. However, existing RFP-based biosensors often suffer from small dynamic ranges, mislocalization and undesired photoconversion. In addition, the choice of available RFP-based biosensors is limited, and development of each biosensor requires substantial effort. Herein, we describe a general and convenient method, which introduces a genetically encoded noncanonical amino acid, 3-aminotyrosine, to the chromophores of green fluorescent protein-like proteins and biosensors for spontaneous and efficient green-to-red conversion. We demonstrated that this method could be used to quickly expand the repertoire of RFP-based biosensors. With little optimization, the 3-aminotyrosine-modified biosensors preserved the molecular brightness, dynamic range and responsiveness of their green fluorescent predecessors. We further applied spectrally resolved biosensors for multiplexed imaging of metabolic dynamics in pancreatic β-cells.

Structure- and mechanism-guided design of single fluorescent protein-based biosensors

Abstract: Intensiometric genetically encoded biosensors, based on allosteric modulation of the fluorescence of a single fluorescent protein, are powerful tools for enabling imaging of neural activities and other cellular biochemical events. The archetypical example of such biosensors is the GCaMP series of Ca2+ biosensors, which have been steadily improved over the past two decades and are now indispensable tools for neuroscience. However, no other biosensors have reached levels of performance, or had revolutionary impacts within specific disciplines, comparable to that of the Ca2+ biosensors. Of the many reasons why this has been the case, a critical one has been a general black-box view of biosensor structure and mechanism. With this Perspective, we aim to summarize what is known about biosensor structure and mechanisms and, based on this foundation, provide guidelines to accelerate the development of a broader range of biosensors with performance comparable to that of the GCaMP series.

Reaction-Based Luminescent Probes for Reactive Sulfur, Oxygen, and Nitrogen Species: Analytical Techniques and Recent Progress.

Abstract: Gasotransmitters and related reactive sulfur, oxygen, and nitrogen species such as nitric oxide (NO), hydrogen sul-fide (H2S), carbon monoxide (CO), hydrogen peroxide (H2O2) and downstream products like peroxynitrite (ONOO–), polysulfides (HSnH), hydroxyl radical (HO•), and azanone (nitroxyl, HNO) are produced under physiological condi-tions and impact cellular signaling and stress. Evolution-ary pressures have driven life to develop sophisticated mechanisms to control the formation and response to this complex reactive species interactome, making it a critical fulcrum that balances health and disease in human physiol-ogy. Driven by a need to understand and measure these types of reactive species, the last decade has witnessed ex-tensive research activity in developing reaction-based probes for optical detection and imaging of reactive sulfur, oxygen, and nitrogen species in living systems. – The cen-tral advantage of this approach is that it is compatible with living cells and animals, thereby enabling t...

Near-Infrared Mitochondria-Targetable Fluorescent Probe for High-Contrast Bioimaging of H2S.

Abstract: To elucidate the complex role of biological H2S and study the mitochondrial damage and some related diseases, effective methods for visualization of H2S in mitochondria and in vivo are urgently needed. In this contribution, a novel near-infrared mitochondria-targetable fluorescence probe MI-H2S for H2S detection was developed. MI-H2S shows rapid detection ability for H2S in pure aqueous solution and outputs a highly selective and sensitive fluorescence-on signal at 663 nm with a large Stokes shift of 141 nm. Bioimaging experiments revealed that the probe has good mitochondrial-targeting ability and high-contrast imaging ability for detecting H2S in living systems. The probe also showed great potential in the detection of H2S during inflammation. All of the results demonstrate that MI-H2S can be applied as an effective probe for the visualization and study of H2S in mitochondria and in vivo.