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Helmholtz Munich | Teresa Rodgriguez-Calvo

Research Group: Type 1 Diabetes Pathology

We use cutting-edge microscopy and image analysis to study the human pancreas in health and disease.

We use cutting-edge microscopy and image analysis to study the human pancreas in health and disease.

The research area is directed at identifying key immunopathological aspects of human type 1 diabetes that will assist in reaching effective prevention or reversal of the disease.

Key to achieving this is to define the interactions between environmental, immune, and intrinsic beta cell factors that underlie the inability of patients with type 1 diabetes to maintain immunological tolerance.

Our work is focused on the human pancreas, defining and characterizing the hallmarks of type 1 diabetes. We closely collaborate with the Network for Pancreatic Organ Donors with Diabetes (nPOD) to study the human pancreas from deceased donors at different stages of their disease. This has allowed us to discover novel pathological aspects, which have opened new lines of investigation that will shape our understanding of the natural history of type 1 diabetes.

Specific Topics

Proinsulin processing and beta cell dysfunction

Under physiological circumstances, proinsulin, the precursor of insulin, is processed very efficiently to insulin. However, high amounts of proinsulin have been detected in the blood and pancreas of patients at risk of developing type 1 diabetes and after diagnosis, indicating a possible disruption of insulin synthesis. We are interested on understanding when these alterations occur and if a possible consequence of this disruption might be the accumulation of incorrect forms of proinsulin in beta cells, which might recognized by the immune system, making beta cells more visible.

The role of the immune system and its interaction with beta cells

Several studies have shown that lymphocytes from patients with type 1 diabetes are able to recognize parts of the proinsulin molecule and destroy beta cells. We are interested in understanding how aberrant proinsulin could be produced and how the immune system recognizes it. This could identify opportunities for therapeutic intervention before beta cells are completely destroyed.

Key mechanisms of viral infection

We are interested on investigating if viruses and anti-viral immune responses can trigger or contribute to the pathogenesis of type 1 diabetes. We study possible molecular mimicry, induction of inflammatory cytokines and related molecules, and the immune response against enteroviruses.

The crosstalk between the duodenum and the pancreas

Alterations in the composition and diversity of the microbial populations in the gut have been observed in individuals who go on to develop type 1 diabetes. Reduced integrity of the gut barrier is also observed in pre- and recently diagnosed diabetic individuals. We think that the underlying genetic predisposition to type 1 diabetes promotes the disruption of immune tolerance, which might lead to the dysregulation of the mucosal barrier in the gut and the development of antigen-specific cells with potential to kill beta cells. We are investigating how the gut and the pancreas interact, and how this could lead to type 1 diabetes.

New image analysis tools to study human tissues

Recently, human pancreas samples have become available through several biobanks worldwide, and this has opened numerous opportunities for scientific discovery. The use of new imaging technologies has unraveled many mysteries of the human pancreas not merely in the presence of disease, but also in physiological conditions. We are interested on applying new technologies and state-art image analysis to the study of the human pancreas and related tissues.

The pancreas innate immune system

The direct role of innate immune cells in the development of type 1 diabetes remains unknown in humans. We are interested on investigating the specific phenotypic signature of pancreatic innate immune cells, together with their dynamic distribution at different stages of the disease.

Scientists of the Research Area

Porträt Teresa Rodriguez

Dr. Teresa Rodriguez-Calvo

Lead Scientist Research Group: Type 1 Diabetes Pathology View profile

Dr. Paola Stephanie Apaolaza Gallegos

Postdoc

Ambra Simoni

Master Student

Latest Publications

Contact

Porträt Teresa Rodriguez

Dr. Teresa Rodriguez-Calvo

Lead Scientist Research Group: Type 1 Diabetes Pathology

Heidemannstraße 1, 80939 München