John Clarke
Washington State University, WA·Pharmacology
Blooms of blue-green algae in lakes and reservoirs release microcystin-LR, the most potent and abundant of the cyanotoxins, into water that people drink and swim in. Exposure has been associated with fatty liver disease and with hepatocellular carcinoma, the most common primary liver cancer.
- Fields
Pharmacology
Biochemistry
Public Health & Epidemiology
- Topics
microcystin-LR
cyanotoxin
harmful algal blooms
- Grants
- 1 known grant, last ended Oct 2026
What they work on
- Define which protein phosphatase 2A-associated pathways mediate microcystin-LR effects on human HepaRG hepatocytes and LX2 stellate cells, the liver's scar-forming cells, co-cultured as 3D spheroids in static and microfluidic systems with pathway modulators.
- Test whether hepatocytes are the primary target of microcystin-LR and stellate cells are activated secondarily by hepatocyte damage, by culturing HepaRG and LX2 cells alone or together in transwell plates.
- Determine how protein phosphatase 2A pathway modulators alter microcystin- and steatohepatitis diet-induced liver pathology in rats fed control or NASH diets.
- Reproduce the original tolerable daily intake regimen of microcystin-LR (40 µg/kg daily for three months) alongside the tumor initiator diethylnitrosamine and a NASH diet to track cirrhosis and hepatocellular carcinoma in healthy versus diseased livers.
- Use phosphoproteomics and single-nuclei transcriptomics to identify the signaling and gene-expression changes underlying persistent fibrotic and carcinogenic reprogramming, and to nominate druggable targets.
More about the research
The concern is sharpened by how common liver disease already is: nonalcoholic fatty liver disease has become the leading chronic liver condition in many countries, so a large population may be meeting this toxin with a liver that is already compromised. Current safety limits were set in healthy animals, leaving open whether they protect people with existing disease.
Why it matters
People living near lakes and reservoirs prone to algal blooms, particularly the large number who already have fatty liver disease, may face greater risk from microcystin than current guidance assumes. By reproducing the dosing behind the tolerable daily intake in animals with pre-existing liver disease, this work could indicate that a lower intake limit is needed for that group, and the molecular pathways identified may point to treatment targets for toxin-driven fibrosis and liver cancer.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Nicholas Davidson
Washington University in St Louis, MO·Medicine & Clinical Research
Determine how the human TM6SF2 E167K variant alters fat loading onto APOB and the release of VLDL from the liver and chylomicrons from the gut, using liver-specific knockout and variant knock-in mice.
Yong-Xu Wang
University of Massachusetts Chan Medical School, MA·Physiology
Test whether a newly identified adipokine, a hormone released by fat tissue, resolves NASH and associated metabolic problems in two different NASH mouse models.
Jian-Min Yuan
University of Pittsburgh, PA·Public Health & Epidemiology
Enroll and follow at least 1,000 patients with non-alcoholic fatty liver disease and advanced fibrosis, tracking liver stiffness by transient elastography every six months for up to five years.
The school
Washington State University: 22 labs on PI Pages, $403M a year on research, 259 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.