Katerina Darwin
New York University, NY·Microbiology & Immunology
Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, is the leading infectious cause of death worldwide and kills nearly 2 million people a year. Treatment takes six to nine months, which makes it hard for patients to finish their antibiotics and encourages drug resistance.
- Fields
Microbiology & Immunology
Biochemistry
Genetics
- Topics
Mycobacterium tuberculosis
aldehydes
aldehyde detoxification
- Grants
- 2 known grants, through Mar 2031
What they work on
- Test whether host-derived aldehydes, reactive products of normal metabolism, act as immune effectors against Mycobacterium tuberculosis, using bacterial and mouse genetics plus biochemistry and cell biology.
- Identify the host sources of metabolic aldehydes that limit microbial growth and the bacterial pathways that confer aldehyde resistance, building on mutants that are hypersensitive to aldehydes.
- Determine, with the TB Alliance, whether frontline TB drugs work better in mice defective for aldehyde detoxification, testing whether an FDA-approved ALDH2 inhibitor could be repurposed for tuberculosis.
- Define how proteins in M. tuberculosis are tagged by the only known bacterial protein-on-protein post-translational modification and how tagged proteins are delivered into the proteasome core protease for degradation.
More about the research
Two questions drive this work: how does the immune system actually kill these bacteria, and what does the bacterium need in order to survive inside an animal for long stretches? One project examines a host weapon, reactive molecules called aldehydes. The other examines a bacterial survival tool, the proteasome, a protein-shredding machine. Both aim to reveal pathways that new drugs could target.
Why it matters
Tuberculosis treatment is long, compliance is difficult, and extensively drug-resistant strains are a growing public concern, including recent US outbreaks. Identifying how the immune system uses metabolic aldehydes to kill bacteria could support repurposing an existing FDA-approved ALDH2 inhibitor to shorten or strengthen therapy. Mapping the bacterial proteasome pathway, which the bacterium needs to persist, could reveal specific targets for new antibiotics.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Anna Tischler
University of Minnesota, MN·Microbiology & Immunology
Build Mycobacterium tuberculosis strains whose phenylalanine-making enzymes can be switched on or off, and use them in macrophage and mouse infections to measure how much the bacterium needs this amino acid pathway during disease.
Karl Schmitz
University of Delaware, DE·Biochemistry
Use phosphoproteomics to identify stress conditions that raise phosphoarginine (pArg) levels in mycobacteria, test whether pArg is needed for stress tolerance, and find the arginine kinases and phosphatases that add and remove it.
Christopher Brown
Weill Medical College of Cornell University, NY·Microbiology & Immunology·Early-career
Expose laboratory and clinical strains of Mycobacterium tuberculosis to air-drying stress and document the resulting changes in metabolism and cell envelope integrity.
The school
New York University: 72 labs on PI Pages, $1.5B a year on research, 540 research doctorates a year.
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