Understanding why AAT deficiency harms the liver and how to fix it
Official title: Mechanisms of Metabolic Dysregulation in ZZ Alpha-1 Antitrypsin Deficiency Associated Liver Disease
Funded at Boston University Medical Campus · NIH-11403995 · Data updated 2026-11-12
A career development program will explore how a genetic liver disease (AAT deficiency) damages liver cells and test ideas that could lead to new treatments for people with ZZ mutations.
Quick facts
| Grant type | Career grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Boston University Medical Campus NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project start | September 1, 2025 |
| Project end | May 31, 2030 |
| Funding year | 2026 |
| Award (this year) | $166,752 |
| NIH project number | 5K08DK140640-02 |
| Project ID | NIH-11403995 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients with ZZ AAT deficiency and their liver cells may contribute samples or data if applicable to the iPSC models used.
✕Less likely to help
Individuals without AAT deficiency or without involvement in the specific iPSC-based models are unlikely to benefit directly.
What this research studies
Over five years, the trainee will work with a team to study the basic biology of ZZ AAT deficiency using patient-derived iPSC-hepatocytes and liver cell models. The project focuses on how misfolded ZAAT proteins trigger stress responses in liver cells and how activating ATF6 signaling affects metabolism and liver health. This work aims to uncover new mechanisms that could be targeted to prevent liver injury and fibrosis while training Dr. Kaserman to become an independent investigator.
Why it matters
Potential benefit: The research could reveal new targets for therapies to treat AATD-related liver disease and help the trainee develop the skills to lead future studies.
How similar studies have gone: Prior work using patient-derived liver cells has provided insight into how AAT deficiency affects metabolism and stress responses, supporting this approach.
Where this research is happening
-
Boston University Medical Campus
Boston, United States Active
Researchers
- Principal investigator: Kaserman, Joseph Emery — Boston University Medical Campus
- Study coordinator: Kaserman, Joseph Emery
Related research
Other NIH-funded projects on the same topics.
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Gene therapy approach to treat Alpha-1 Antitrypsin Deficiency
A gene therapy approach is being developed to treat Alpha-1 Antitrypsin deficiency, a lung disease, with the aim of providing a lasting source of the protective AAT protein.
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Treating alpha-1 antitrypsin deficiency by targeting cellular protein-folding pathways
This project uses small molecules to fix how cells fold alpha-1 antitrypsin so people with different genetic forms of alpha-1 antitrypsin deficiency may keep healthier livers and lungs.
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Managing Alpha-1-Antitrypsin Deficiency through Protein Pathways
This study is looking at how to better treat Alpha-1-Antitrypsin Deficiency (AATD) by understanding how different gene variations affect the disease and testing new ways to help the body make the AAT protein work better, which could lead to improved treatments for patients like you.
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Creating a new tool to correct a genetic defect causing alpha-1 antitrypsin deficiency.
This study is testing a new way to fix the genetic problem that causes alpha-1 antitrypsin deficiency by using a special tool to edit the gene in your liver, which could lead to better and safer treatments for people with this condition.
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Prediction score for death or lung transplant in emphysema caused by alpha-1 antitrypsin deficiency
This study tests a new prediction tool to identify people with emphysema due to alpha-1-antitrypsin deficiency who are at high risk of death or needing a lung transplant.
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Two weekly doses of Alpha1-Proteinase Inhibitor by injection compared with standard IV dose in alpha-1 antitrypsin deficiency
A 'how it works' test to see if two weekly subcutaneous doses are as safe and help the body process the medicine as well as the standard IV dose for adults with AAT deficiency.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.