Type 1 Diabetes Pathology

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.

Whole-Slide Image Analysis of the pancreas to elucidate the cause of human type 1 diabetes

Altered beta cell prohormone processing in type 1 diabetes

The role of the innate and adaptive immune system in the pathogenesis of type 1 diabetes

Alterations in gut permeability and epithelial barrier function in type 1 diabetes

The role of viruses as potential triggers and contributors to type 1 diabetes disease development

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.

Teresa Rodriguez-Calvo (Group leader research area type 1 diabetes pathology)

“My group works in close collaboration with several tissue biorepositories worldwide, which provide valuable samples from non-diabetic and diabetic donors. Together, we work towards understanding how type 1 diabetes develops in order to move the field forward and closer to a cure.“

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Dr. Teresa Rodriguez-Calvo

Lead Scientist Research Group: Type 1 Diabetes Pathology

Profil anzeigen

Dr. Paola Stephanie Apaolaza Gallegos

Senior Scientist

Dr. Ery Petropolou

Senior Postdoc

Patricia Velado

PhD Student

Judit Rovira i Rubio

Technical Assistant

Samira Zamani

Technical Assistant

Summer get-together 2023: Laser Tag

Summer get-together 2023: Laser Tag

Visit to a brewery 2023

Lunch at a beer garden 2022

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Summer get-together 2022: Amusement park

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Mallone R, Sims E, Achenbach P, Mathieu C, Pugliese A, Atkinson M, Dutta S, Evans-Molina C, Klatzmann D, Koralova A, Long SA, Overbergh L, Rodriguez-Calvo T, Ziegler AG, You S.

Emerging Concepts and Success Stories in Type 1 Diabetes Research: A Road Map for a Bright Future.

Apaolaza PS, Chen YC, Grewal K, Lurz Y, Boulassel S, Verchere CB, Rodriguez-Calvo T.

Quantitative analysis of islet prohormone convertase 1/3 expression in human pancreas donors with diabetes

Vecchio F, Carré A, Korenkov D, Zhou Z, Apaolaza P, Tuomela S, Burgos-Morales O, Snowhite I, Perez-Hernandez J, Brandao B, Afonso G, Halliez C, Kaddis J, Kent SC, Nakayama M, Richardson SJ, Vinh J, Verdier Y, Laiho J, Scharfmann R, Solimena M, Marinicova Z, Bismuth E, Lucidarme N, Sanchez J, Bustamante C, Gomez P, Buus S; nPOD-Virus Working Group; You S, Pugliese A, Hyoty H, Rodriguez-Calvo T, Flodstrom-Tullberg M, Mallone R.

Coxsackievirus infection induces direct pancreatic β cell killing but poor antiviral CD8+ T cell responses.

Apaolaza PS, Balcacean D, Zapardiel-Gonzalo J, Rodriguez-Calvo T.

The extent and magnitude of islet T cell infiltration as powerful tools to define the progression to type 1 diabetes

Apaolaza PS, Petropoulou PI, Rodriguez-Calvo T.

Whole-Slide Image Analysis of Human Pancreas Samples to Elucidate the Immunopathogenesis of Type 1 Diabetes Using the QuPath Software

Paola S Apaolaza, Diana Balcacean, Jose Zapardiel-Gonzalo, Grace Nelson, Nataliya Lenchik, Pouria Akhbari, Ivan Gerling, Sarah J Richardson, Teresa Rodriguez-Calvo and the nPOD-Virus Group

Islet expression of type I interferon response sensors is associated with immune infiltration and viral infection in type 1 diabetes

Teresa Rodriguez-Calvo, Yi-Chun Chen, C Bruce Verchere, Leena Haataja, Peter Arvan, Pia Leete, Sarah J Richardson, Noel G Morgan, Wei-Jun Qian, Alberto Pugliese, Mark Atkinson, Carmella Evans-Molina and Emily K Sims.

Altered β-Cell Prohormone Processing and Secretion in Type 1 Diabetes

Complete list here: https://pubmed.ncbi.nlm.nih.gov/?term=rodriguez-calvo+t&sort=date

Research Group: Type 1 Diabetes Pathology

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Specific Topics

Proinsulin processing and beta cell dysfunction

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

Key mechanisms of viral infection

The crosstalk between the duodenum and the pancreas

New image analysis tools to study human tissues

The pancreas innate immune system

Teresa Rodriguez-Calvo (Group leader research area type 1 diabetes pathology)

Media Coverage

La progresión de la diabetes tipo 1 y la infiltración linfocitaria

Heard on the street: The sugar science

New publication

Podcast: The sugar science

Collaboration with Zeiss

Celebration of the 100 years of the discovery of insulin

DZD best conference contribution award 2020

3rd place on the INNODIA / INNODIA HARVEST Young Scientists Award competition

Scientists of the Research Area

Fun with the team

Latest Publications

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