Ambika Bhagi
University of Minnesota, MN·Biochemistry
Cells constantly sense and respond to redox stress, chemical changes caused by reactive molecules that add or remove electrons. Signaling molecules such as nitric oxide (NO), carbon monoxide (CO) and reactive oxygen species are highly reactive, so it is surprising that cells use them to send precise signals without many unwanted side reactions.
- Fields
Biochemistry
Chemistry
Microbiology & Immunology
- Topics
redox signaling
redox biology
signal transduction
- Grants
- 1 known grant, through Mar 2031
What they work on
- Use structure-guided protein design to reprogram how sensitive and selective the heme iron sensor enzymes DosS and DosT are to low oxygen, nitric oxide and carbon monoxide.
- Determine how changing DosS and DosT sensing affects bacterial redox signaling and cell behavior, including the signal to enter dormancy, using enzymology and spectroscopy.
- Apply structural biology techniques to reveal the molecular basis of signal transduction in DosS and DosT, that is, how detecting a gas switches the enzyme's activity.
- Develop redox-selective activity-based probes, chemical tags that react only with active enzymes, to measure active and inactive sensor levels inside cells.
More about the research
This raises two questions: what makes redox signaling so specific, and can scientists deliberately rewire these pathways to restore or disrupt a cell's redox balance? Redox imbalance is linked to diseases ranging from neurological disorders to cancer, and the lab's long-term goal is to develop molecular ways to reprogram how cells sense and signal these molecules.
Why it matters
Many diseases, including cancer, cardiovascular disorders and neurological conditions such as Alzheimer's, are linked to redox imbalance in cells. Learning how sensor enzymes pick out specific redox signals, and how to redesign them, could inform molecular strategies to restore normal redox balance in diseased cells. These strategies could eventually guide new types of therapy, though that would require further work.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Stephen Wiley Ragsdale
University of Michigan, MI·Biochemistry
Determine how the heme oxygenase-2 (HO2) catalytic core coordinates heme sequestration with its own lysosomal breakdown during heme deficiency, and test whether inducible HO1 also sequesters heme.
Gayan Wijeratne
University of Alabama, AL·Chemistry
Synthesize heme-nitrogen oxide model complexes with systematically varied ligands in the primary and secondary coordination spheres, to find which features of the heme center control the geometry and electronic structure of these intermediates.
Mark Gladwin
University of Maryland, Baltimore, MD·Medicine & Clinical Research
Test whether airway epithelial cytoglobin, a heme protein of unknown function, forms a complex with cilia and nitric oxide synthase to tune nitric oxide signaling, using cytoglobin knockout, H81Q gain-of-function and K116E loss-of-function mice, zebrafish, and PCD patient airway cells.
The school
University of Minnesota: 88 labs on PI Pages, $1.4B a year on research, 722 research doctorates a year.
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