SUMMARY
The research of Kirk J. Wangensteen, M.D., Ph.D., focuses on defining genetic factors involved in liver disease progression and the development of liver cancer. The goal of his research program is to make clinical impacts by improving the understanding of disease biology and by developing new therapeutics.
Lab projects incorporate early discovery using genetic screens in mice livers, mechanistic work to identify gene function and regulation of genetic pathways. Other endeavors involve collaborative work to apply genetic tools for gene delivery and screening, as well as human subjects research to identify genetic associations for liver diseases in patients.
One current research project in the Wangensteen lab is based on results from a genetic screen to identify genes that can accelerate or inhibit liver regeneration. Through this screening process, the lab discovered a gene that is required for liver hepatocytes to divide in response to severe liver injury. Yet the same gene is dispensable for normal liver development and homeostasis. The team also discovered that the gene is required for cancer to form. It may be possible to target this gene for cancer prevention in settings with an inherent elevated risk of cancer, such as in cirrhosis.
Focus areas
- Characterizing genetic pathways involved in liver repopulation and homeostasis. The Wangensteen lab uses a mouse model of liver injury and repopulation that repeats many features of liver disease that occur in patients. This model enables the disruption of gene function in many genes using a parallel genetic assay with a CRISPR-Cas9 system that Dr. Wangensteen and colleagues engineered. Through genetic screens, the lab identifies novel mechanisms of liver regeneration and potential targets for therapy.
- Identifying targets to treat or prevent liver cancer. The Wangensteen lab performs genetic screens in mice to systematically target gene expression levels to better understand how genes cooperate to drive cancer. His team is working to identify tumor-intrinsic gene pathways that the immune system recognizes.
- Genetic association studies in patients with liver cancer. Dr. Wangensteen leads a multidisciplinary team that is studying whether patients with liver cancer harbor genetic variants that are associated with cancer risk.
Significance to patient care
The liver is the central metabolic hub of the body. Diseases of the liver cause morbidity and mortality worldwide. Hepatocellular carcinoma (HCC) is a devastating and prevalent cancer of the liver with high mortality. Effective treatments for liver diseases and HCC are lacking. The lab's team hopes to improve outcomes for patients with liver disease by increasing understanding of the complex systems that keep the liver healthy or that go awry in disease.
Dr. Wangensteen is a physician-scientist who subspecializes in the genetics of gastrointestinal (GI) diseases, including hereditary cancer syndromes and monogenic diseases of the liver. He regularly recommends genetic testing to patients to help them better understand disease etiology, such as with early-onset cancer. He performs diagnostic tests, counsels patients and evaluates laboratory results. Dr. Wangensteen is using both lab-based and bedside approaches to improve outcomes in GI and liver diseases.
Professional highlights
- Medical Student Teaching Award, Gastroenterology Division, University of Pennsylvania, 2020.
- Gastroenterology Faculty Research Award, University of Pennsylvania, 2019.
- Young Physician-Scientist Award, The American Society for Clinical Investigation, 2018.
- Junior Investigator Award, International Liver Cancer Association, 2018.
- Beckman Young Investigator Award, University of Pennsylvania, 2019.