Bharat Bhushan
University of Pittsburgh, PA·Pharmacology
Acetaminophen (APAP) overdose is the leading cause of acute liver failure in the United States. The only drug treatment, N-acetylcysteine (NAC), works only when patients arrive early, and most arrive late.
- Fields
Pharmacology
Medicine & Clinical Research
Physiology
- Topics
acetaminophen
drug-induced liver injury
acute liver failure
- Grants
- 1 known grant, through Dec 2027
What they work on
- Determine the role of EGFR in liver injury and regeneration after acetaminophen overdose using mice lacking EGFR in hepatocytes and receptor-activation strategies, and identify how EGFR worsens injury.
- Test whether MET, the receptor for hepatocyte growth factor, directly suppresses progression of acetaminophen-induced liver injury and promotes regeneration, using hepatocyte-specific knockout and activation approaches.
- Evaluate the clinically approved EGFR inhibitor afatinib and MET-targeted interventions in mice, focusing on late treatment when N-acetylcysteine is no longer effective.
- Validate the effects of these interventions and the underlying mechanisms in a primary human hepatocyte model of acetaminophen-induced liver injury.
More about the research
Doctors need treatments that work at later stages, either by stopping the spread of injury or by boosting the liver's ability to regrow. Two growth factor receptors on liver cells, EGFR and MET, are thought to drive regrowth after part of a healthy liver is surgically removed. Their roles after an overdose are poorly understood. In an overdose, massive injury and inflammation dominate.
Why it matters
Patients with acetaminophen-induced acute liver failure who seek care late have no effective drug option. This work could show whether afatinib, an EGFR inhibitor already approved for clinical use, or treatments targeting MET might be repurposed to limit liver damage and support liver regrowth in these late-presenting patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Ankita Srivastava
Thomas Jefferson University, PA·Physiology
Test whether chronic ethanol upsets the balance between metabolic adjustments and hepatocyte division after partial hepatectomy (PHx, surgical removal of part of the liver) in rats.
Srivalleesha Mallidi
Tufts University, MA·Biomedical Engineering
Synthesize and characterize Verosite nanodroplets — perfluorocarbon particles carrying the photosensitizer verteporfin, oxygen, and indocyanine green dye — and optimize their stability and light-triggered liquid-to-gas conversion.
Anne Vonada
Oregon Health & Science University, OR·Medicine & Clinical Research
Render donor hepatocytes resistant to acetaminophen by knocking out Cypor, the gene needed to convert the drug into a toxic form, and test drug-driven selection of donor cells in mouse models of alkaptonuria and gyrate atrophy.
The school
University of Pittsburgh: 83 labs on PI Pages, $1.5B a year on research, 403 research doctorates a year.
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