Stephen Miller
University of Massachusetts Chan Medical School, MA·Chemistry
Fireflies glow because an enzyme, luciferase, chemically oxidizes a small molecule called D-luciferin and releases a photon. Put both parts into a mouse and the animal glows wherever the enzyme is active, so a sensitive camera can report on gene activity, enzyme function, or where injected cells are growing.
- Fields
Chemistry
Biochemistry
Biomedical Engineering
- Topics
bioluminescence
luciferin
luciferase
- Grants
- 1 known grant, through Mar 2030
What they work on
- Design and synthesize new luciferin substrates, the small molecules that firefly luciferase oxidizes to emit light, whose emission extends into the near infrared, where light penetrates animal tissue most effectively.
- Engineer luciferase enzymes that efficiently accept these new near-infrared luciferins, so that the substrate and enzyme work as a matched pair.
- Improve substrate access to the enzyme by addressing binding affinity, cell permeability, solubility, chemical stability, and active removal of luciferins by cellular drug efflux pumps.
- Characterize the photophysical properties of new luciferins, including the efficiency with which the reaction yields photons and the wavelength emitted, to maximize usable light output for imaging in live animals.
More about the research
Because no excitation light is needed and tissue produces almost no background glow of its own, this bioluminescence approach is often more sensitive than fluorescence, and it is cheap and robust enough for routine drug screening. Its limits come from the chemistry: how much light escapes a mouse depends on the color of the emitted light, and on whether the luciferin substrate can reach the enzyme at all.
Why it matters
Brighter, redder bioluminescent reporters could let researchers watch processes deep inside live mice that are currently invisible, such as where tumor cells travel or when a gene turns on, using only a camera and no surgery. Because bioluminescence assays are inexpensive and widely used in drug discovery, more sensitive luciferin-luciferase pairs could improve the sensitivity of screening for new drugs as well as animal imaging studies.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jung-Jae Lee
University of Colorado Denver/Anschutz Medical Campus, CO·Chemistry
Develop near-infrared chemiluminescent and fluorescent chitosan nanoparticles that are stored cold and activated by body heat, giving a self-illuminating contrast agent that needs no external light source.
Thomas Teets
University of Houston, TX·Chemistry
Increase the light-emission speed of blue-emitting platinum aryl acetylide complexes through a "secondary heavy-metal effect," attaching coinage metals or gold–carbon bonds to the molecule's periphery.
Haiying Liu
Michigan Technological University, MI·Chemistry
Design and synthesize near-infrared BODIPY dye probes that emit two colors whose ratio reports viscosity, with improved water solubility, stability and ability to enter cells.
The school
University of Massachusetts Chan Medical School: 29 labs on PI Pages, $350M a year on research, 55 research doctorates a year.
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