Srinath Sanda, M.D.
Dr. Sanda is a pediatric endocrinologist at the UCSF Benioff Children’s Hospital and the UCSF Diabetes Center. He treats children and young adults with diabetes and other endocrine conditions including disorders of the pituitary, thyroid, parathyroid and adrenal glands.
Dr. Sanda’s research focuses on the nexus of immunology and beta cell biology as it relates to diabetes. The goal is to conduct translational research that leads to new therapeutic approaches to diabetes. His current work focuses on three different areas:
1. The role of the IL-1b pathway and monocytes in diabetes pathogenesis
IL-1b is a prototypical inflammatory cytokine that has been shown to induce beta cell apoptosis. Monocytes are peripheral blood leukocytes that are both a major source and target of IL-1b. Both appear to be important to the pathogenesis of type 1 diabetes, type 2 diabetes, and possibly cystic fibrosis related diabetes (CFRD). We are investigating how various perturbations to the IL-1b pathway affect monocyte function and migration and how this correlates with immune modulation and disease state. We use in vitro manipulations of human blood samples, samples from in vivo human clinical studies, and autopsied human pancreas sections to conduct our experiments. The goal of these projects is to understand whether IL-1b and monocytes may be suitable therapeutic targets or biomarkers for clinical immune modulating trials. Our current projects in this area include:
- The analysis of immune responses to in vivo hyperglycemia, a known inducer of IL-1b.
- Monocyte responses to in vitro and in vivo IL-1R antagonism, vitamin D supplementation, and tyrosine kinase inhibition.
- Identifying IL-1b and related proteins in subjects with CFRD by analyzing human pancreas sections.
2. The role of genetic polymorphisms in beta cell function
The determinants of the natural decline in beta cell function in humans with type 1 diabetes are poorly understood. The rapid loss of beta cell function may be associated with a greater risk of vascular complications. We hypothesize that intrinsic phenotypes of human beta cells may be important in understanding the natural history of type 1 diabetes. We have observed that polymorphisms in G6PC2 may predict the decline in beta cell function in patients with type 1 diabetes. We are moving towards analyzing larger cohorts. If we confirm our preliminary findings, we believe that we could use genotyping to identify patients at high risk of developing vascular complications.
3. Expression of cell cycle transcription factors in the human pancreas
We have begun studying the expression of Bmi1 and p16INK4A in human pancreas sections. The goal is to understand the cellular distribution and age-dependent expression of these proteins in humans. We are also interested in understanding the role of inflammation in regulating the expression of these proteins. Animal models suggest that these transcription factors may be important to beta cell replication particularly in response to GLP-1 therapy. The results of this work could be helpful in defining the utility of GLP-1 therapy in beta cell regeneration.