Michael Pacold
New York University, NY·Biochemistry
Some places in the body are short on nutrients and oxygen. Brain fluid holds little serine and glycine, amino acids that cells need to make proteins, DNA building blocks and antioxidants.
- Fields
Biochemistry
Biology
Pharmacology
- Topics
cancer metabolism
nutrient limitation
hypoxia
- Grants
- 1 known grant, through Aug 2027
What they work on
- Identify metabolic adaptations, such as alternative sources of serine and glycine, that cells need to enter and survive in the low-nutrient brain, and determine whether these arise before or after brain entry.
- Test small-molecule inhibitors against these metabolic adaptations as proof of concept for preventing disease from cells entering the brain, such as autoimmune disease and brain metastases.
- Define the enzymes, intermediates and regulation of the newly discovered mammalian Coenzyme Q10 headgroup synthesis pathway, and how cells make just enough coenzyme for growth.
- Use newly developed isotope-labeled gas tracing to discover oxygen-dependent metabolic pathways that cells rely on to survive in low-oxygen environments.
More about the research
Most tissues, including the brain and bone marrow, also contain less oxygen than ordinary air. Cells living or growing there must adapt. Nutrient and oxygen shortages also play a part in autoimmune disease, heart disease and cancer. This project looks for the metabolic tricks cells use to survive these conditions, and for drugs that block them.
Why it matters
Blocking the metabolic adaptations that let cells invade the brain could help prevent diseases caused by such cells, from autoimmune disease to brain metastases in cancer. Mapping Coenzyme Q10 synthesis and oxygen-dependent pathways could reveal new weak points in cell metabolism. These may point to drug targets for diseases in which low oxygen or nutrient shortage plays a role.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Sergey Krupenko
University of North Carolina at Chapel Hill, NC·Biochemistry
Characterize the catalytic activity and stability of ALDH1L1 enzyme variants encoded by common human haplotypes, testing whether protein-altering SNPs impair conversion of 10-formyl-THF to THF.
Isaac Marin-Valencia
Icahn School of Medicine at Mount Sinai, NY·Neuroscience
Determine when two proposed metabolic switches start and how long they last in the developing mouse brain: glycolysis to oxidative metabolism, and the propionate-to-succinyl-CoA pathway to pyruvate carboxylation. The project will use 13C isotope tracing.
Rovshan Sadygov
University of Texas Medical Branch at Galveston, TX·Biochemistry
Develop methods to estimate protein turnover from the deuterium labeling of fragment ions in tandem mass spectra, which are less distorted by space-charging, limited dynamic range and co-eluting contaminants than intact peptide ions.
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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