Our hybrid wet:dry lab uses bioinformatics approaches to identify genetic variants of interest and validates their functional impact on immune cells and pancreatic beta cells in the laboratory.

The Shapiro laboratory is currently funded to study: 
 1) Germline genetic variants predicting response to immunotherapies for T1D
 2) Somatic variants in the pancreas and immune cells of organ donors with T1D

1) We collaborate with major T1D clinical trial consortia, T1D TrialNet (TN) and Immune Tolerance Network (ITN), to re-analyze existing datasets including precision genotyping microarray versus metabolic or ex vivo immune phenotyping outcomes. Correlations between genetics and response signatures identified through clinical trial datasets will be validated by the laboratory using in vitro models of modified gene expression, mRNA splicing, or protein function (CRISPR/Cas9, siRNA, blocking antibodies) in human peripheral blood mononuclear cells (PBMCs). Precision drug dosing or drug selection strategies will be investigated both in vitro and in vivo, using murine models to demonstrate rescue of drug efficacy across genotypes.

2) We also work with investigators from the Network for Pancreatic Organ donors with Diabetes (nPOD) and Human Pancreas Analysis Program (HPAP) to re-analyze bulk and single cell RNA and DNA sequencing data for somatic mutations that may promote neoantigen production by beta cells or proliferation/survival of autoreactive lymphocytes. Mutations enriched in autoantibody-positive pre-T1D or T1D donors will be modeled in vitro in identified immune or pancreatic cell types to study impacts on lymphocyte function and/or destruction of beta cells.