Current Type 1 Diabetes Research

Human Cell Beta Biology

Current basic research in the Harlan lab focuses on exploring beta cell biology and the anti-beta cell immune response underlying type 1 diabetes (T1D).  We have developed innovative techniques to sort human pancreatic islet endocrine cell subsets, including from donors with type 1 and type 2 diabetes, to determine the transcriptome from those purified cells.

Human islet-infiltrating T cell biology: Reactivity, structure & function

Fully characterizing T lymphocytes procured from the islets of individuals who have died after being diagnosed with type 1 diabetes.

Improving islet isolation of pancreatic islets in T1D to assess alpha cell function and gene expression  

As investigators studying pancreata procured from individuals with long-standing T1D, the Harlan lab has uncovered invaluable information about pancreatic beta cells and islet-infiltrating T cells. We have also learned that the islet isolation process is quite unlike that of non-diabetic donors without T1D and that alpha cells from donors with T1D are also quite different. 

Insulin Dependent Diabetes Mellitus

Alpha cell plasticity in human type 1 diabetes

Addressing whether alpha cells might display evidence of plasticity, e.g., whether the metabolic and immunologic pressures associated with T1D might lead to an alpha cell phenotype intermediate between that found in a control subject’s alpha and beta cells. 

Tolerance Mechanisms and Organ/Tissue Transplantation

Type 1 diabetes humanized mouse avatars

We are recapitulating T1D in humanized mice using induced pluripotent stem (iPS) cells derived from T1D donors to generate beta cells, thymic epithelium, and hematopoietic stem cells. These cells are then transplanted into immunodeficient mice to observe their interaction.

Stage-specific beta cell response and biomarker profile during virus-induced type 1 diabetes

We are using novel technology to recover small RNA from circulating plasma and perform RNAseq in the virus-induced BBDR rat and in our new model of Coxsackie B4-infected immunodeficient mice engrafted with human islets, which will permit us to identify human miRNA signatures.

Advanced biomaterials and delivery systems for islet encapsulation

Investigating the ability of various capsules to protect porcine islets from rejection when transplanted into immunocompetent rats.