Siva Kasinathan, MD, PhD
2023 Recipient of the Gary S. Gilkeson Career Development Award
Stanford University School of Medicine
Project Title: T lymphocyte somatic genetic variation in lupus
Mentor(s): Paul J. (P.J.) Utz, MD and Ansuman Satpathy, MD, PhD
About the Researcher
Siva Kasinathan, MD, PhD is a Clinical Fellow in Pediatric Rheumatology at the Stanford
University School of Medicine and Lucile Packard Children’s Hospital at Stanford. He completed
MD-PhD training at the University of Washington and Fred Hutchinson Cancer Center in Seattle.
His graduate research with Dr. Steven Henikoff included the innovation of several genome-scale
technologies for chromatin profiling and generated new insights in centromere biology and gene
regulation. Dr. Kasinathan then went on to train in clinical pediatrics at Stanford. He continued to develop genomic technologies, this time with a focus on single-molecule sequencing in collaboration with Dr. Vijay Ramani’s group at the Gladstone Institutes.
Dr. Kasinathan’s current research interests span somatic genetics, epigenomics, and immune dysregulation. His ongoing work with Dr. Ansuman Satpathy at Stanford involves developing and using sensitive methods to analyze immunogenetic variation in lupus. As a physician-scientist, he is committed to a career that combines clinical medicine and basic research to better understand the molecular basis of autoimmunity and improve long-term outcomes in rheumatic diseases such as lupus
Lupus is a disease caused by genes and factors in the environment. Not everyone who has lupus has a family member with the same disease. In fact, inherited genetic changes explain only a fraction of lupus cases. Changes in our genes that are not inherited, called “somatic mutations,” may also be responsible for lupus. Somatic mutations can be caused by things like UV light. These mutations can cause cancer and studying them has helped find new treatments. We don’t know very much about somatic mutations in lupus because they are hard to study. We think that researching these mutations in the immune system can help us better understand lupus.
We recently developed gene sequencing tools to find somatic mutations. These new tools will let us test for the first time if somatic mutations play a role in lupus. In this research project, we will look at mutations in T cells. T cells are part of the immune system and are very important in lupus. We will compare T cells from people who have lupus to T cells from people who are healthy. First, we will look at groups of immune cells to see which mutations are only in T cells. Then, we will look at single T cells to see if somatic mutations change how they work in lupus. We hope this research will help us develop personalized tests and treatments for lupus.