How Do Cancer Cell Mutations Affect Genes?
Article Summary
- Dr. Alejandro Villarino’s V Foundation early-career investigator award will fund an analysis of T-cell malignancies.
- His research will center on how genetic mutations associated with T-cell leukemias and lymphomas affect gene function.
- Using the reverse genetic screen platform he built, Dr. Villarino will test for 75 cancer-associated mutations in the STAT3 gene.
After 20 years of studying infectious and autoimmune diseases, Alejandro Villarino, Ph.D., wanted a change.
Dr. Villarino shifted his career focus to oncology research at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, where he is an assistant professor of microbiology and immunology. His achievements in the field have been highlighted by a $200,000 grant from the V Foundation.
Dr. Villarino received the organization’s early-career investigator award for his proposed comprehensive molecular and therapeutic assessment of STAT3-driven T-cell malignancies.
“It’s been an invigorating journey to enter a new field,” Dr. Villarino said. “I’m constantly learning as I move to the complex world of cancer research. This grant validates our efforts, and we are excited to take the next steps in our work.”
From Infectious and Autoimmune Diseases to Cancer Research
Initially, Dr. Villarino studied parasites such as toxoplasma and malaria before gravitating to the immunology of infectious diseases. As a postdoctoral fellow, he shifted to autoimmune diseases.
Dr. Villarino’s research centered on the cellular pathways that T cells use to communicate with one another. He realized the same pathways were hyperactive in T-cell leukemias and lymphomas.
“Immunology is now at the cutting edge of cancer research,” Dr. Villarino said. “People have realized that training the immune system to find and attack cancer cells can be a durable way to help people. Sylvester understands this message and wants to grow its status in immunology research, making it an ideal fit for me.”
Gene Mutations in Cancer Cells
With the V Foundation grant, Dr. Villarino will study how genetic mutations associated with T-cell leukemias and lymphomas affect the function of implicated genes. Genome sequencing can identify specific genetic mutations in cancer patients. Understanding how these mutations alter the function of the affected genes is an ongoing process.
“We’re trying to develop an experimental platform that allows us to assess the functional consequences for hundreds, potentially thousands, of mutations all at once,” Dr. Villarino said. “The technology we are using is called single-cell sequencing, which allows you to see all genes expressed in individual cells. Based on this technology, we have developed a reverse genetic screen platform that can ascribe functional consequences for all known mutations in any given gene in about a week.”
Dr. Villarino will use the STAT3 gene as the first test case. STAT3 is often mutated in blood cancers, specifically T-cell cancers. Dr. Villarino has studied the JAK-STAT signaling pathways for his entire career. The platform will be used to understand the mutations and enable drug testing across thousands of mutations.
“We are heading toward precision medicine as we aim to match individual genetic profiles to the treatments that are most likely to work for these patients,” Dr. Villarino said. “Different mutations often cause different diseases and don’t respond to the same treatments. If we can understand how different classes of mutations are similar or different, we could link those classes to specific treatments.”
In Vitro and In Vivo Testing
The grant will fund testing for 75 cancer-associated mutations in STAT3 using the reverse genetic screen platform Dr. Villarino built. The platform is designed so the lab can study these mutations in preclinical models.
“We’re going to run our platform through its paces in vitro, then go in vivo to test different drugs across the mutant roster,” Dr. Villarino said. “Hopefully, at the end of this process, we can learn something about T-cell leukemia and lymphomas that will genuinely benefit people.”
Ultimately, Dr. Villarino aims to assign treatments to individual mutations or mutation classes. He also wants to take the research to a clinical trial setting, where treatment is prescribed based on genetic makeup. The platform designed by Dr. Villarino is also scalable and adaptable. New mutations can be easily added and, in theory, any oncogene can be studied in any cell type, he said.
Tags: 2024 V Foundation, Dr. Alejandro Villarino, Leukemia, lymphoma, microbiology and immunology, Sylvester Comprehensive Cancer Center, V Foundation