Sajid Khan, MD, Chief of Hepato-Pancreato-Biliary & Mixed Tumors, has been awarded a highly competitive R01 grant from the National Institutes of Health (NIH)-National Cancer Institute (NCI) for the study titled “Role and Regulation of Asparagine in Colorectal Cancer.” This groundbreaking research aims to uncover the mechanisms by which asparagine influences sex-specific differences in the progression of advanced colorectal cancer.
Dr. Khan — who additionally serves as Co-Director of Team Science at Yale School of Medicine — shares the role of Principal Investigator with Caroline Johnson, PhD Associate Professor of Epidemiology (Environmental Health Sciences) at Yale School of Public Health. This is the duo’s third NIH-funded grant as Co-Principal Investigators, all of which have employed a Team Science approach, emphasizing the importance of collaborative, interdisciplinary research in tackling complex health challenges.
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. The study will explore the causal relationship between asparagine production—both intracellular and extracellular—and tumor growth, while accounting for sex-specific biological differences.
The team hypothesizes that asparagine synthetase (ASNS), an enzyme tied to asparagine production, interacts with G-protein coupled estrogen receptor 1 (GPER1) to influence tumor progression differently in women and men with advanced stage (III and IV) cancers. Their research will focus on three aims:
- Investigating ASNS and GPER1 as sex-specific biomarkers using clinical cohorts.
- Studying how ASNS and GPER1 regulate tumor growth and liver metastasis in sex-specific mouse models.
- Examining the impact of dietary asparagine and microbiota-derived asparagine on tumor development.
By advancing our understanding of these mechanisms, the study aims to inform targeted therapies and improve outcomes for patients with advanced stage colorectal cancer including those with liver metastasis.
Congratulations to Dr. Khan and Dr. Johnson on this remarkable achievement and their commitment to advancing cancer research.