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David M. Harlan, MD: Current Diabetes Research

Human Cell Beta Biology

Our current basic research focuses on exploring beta cell biology and the anti-beta cell immune response underlying type 1 diabetes (T1D).  The Harlan Lab has 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, and 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, we have uncovered invaluable information about the pancreatic beta cells and the islet infiltrating T cells.  We have also learned that the islet isolation process is quite unlike that from donors without T1D, and that alpha cells from donors with T1D are also quite different. 

Improving Diabetes Care Delivery Systems

T1D Exchange

Designed to harness the power of type 1 diabetes patients to help themselves, clinicians and researchers have improved patient management and conducted new and collaborative research, in real time.

Psychological excellence in diabetes training initiative  

Our goal is to prepare more behavioral psychologists to care for people with diabetes and systematically investigate relevant research questions.

Insulin Dependent Diabetes Mellitus

Alpha cell plasticity in human T1D

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

Focusing on 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 that will be transplanted into immunodeficient mice.

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

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 that 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.

HLA Class II antigen processing and presentation pathway components demonstrated by transcriptome and protein analyses of beta cells from donors with type 1 diabetes

Studying the islets of donors with type 1 diabetes, we definitively show that beta cells express these important immune pathway gene products, resolving a three decades long debate.  LEARN MORE 

Human islets expressing HNF1A variant have defective beta cell transcriptional regulatory networks

Isolating donated islets from a young man who had been treated for 17 years for presumed T1D, we found that a rare genetic defect had caused his beta cells to function improperly.  LEARN MORE

Alpha cell function and gene expression are compromised in type 1 diabetes

To better understand the functional and molecular properties of islets from donors with T1D, this research used an approach that studied the pancreas and isolated islets from the same donor, allowing better analysis of the development, properties and behavior of the islets.  LEARN MORE