von Herrath Lab

von Herrath Lab

"Type 1 diabetes is particularly tragic because it usually starts in childhood and its effects worsen with time. It can lead to organ damage, blindness and other terrible side effects. That's why I focus so heavily on this disease. I'm trained as a physician and I saw what it can do." — Matthias von Herrath, M.D. // Professor
Vice President and Head, Diabetes R&D Center, Novo Nordisk, Inc.


Dr. Matthias von Herrath is committed to clinical translation of immune-based interventions in autoimmune and metabolic diseases, the latter in particular being an exciting emerging field. His expertise and main strength is working at the interface of experimental research to interpret and refine early phase I/II clinical trials in order to optimize strategies for phase 3 trials and drug approval. This comprises translation from various animal models to human interventions, optimization of immunotherapies and their relative ranking, assessment of combination therapies, development of biomarkers as primary or secondary outcomes, induction of antigen specific tolerance in autoimmunity, regulatory cells and clinical T cell assays. In order to be better able to pursue his goal of clinical translation, Dr. von Herrath accepted the position of Vice President and Head of NovoNordisk’s diabetes R&D Center in Seattle in autumn of 2011. At NovoNordisk, he built the diabetes translational unit, which is based on less conventional and innovative design.

Understanding disease pathology remains very close to Dr. von Herrath’s heart and NovoNordisk enabled him to keep an appointment at La Jolla Institute, where he pursues NIH-funded research on the pathology of type 1 and 2 diabetes as part of the national pancreatic organ donor network (nPOD). This is a multinational collaborative effort where data are shared in real time and no intellectual property yet lots of new knowledge on the pathology of type 1 and 2 diabetes is being generated. It is a unique new collaborative paradigm for academic and also industry settings.

From The Lab

Aug 26, 2020

Blocking nerve signals to the pancreas halts type 1 diabetes onset in mice

New LJI discovery could help explain patterns of cell death in many autoimmune diseases
Dec 12, 2018 // Expertscape

LJI Professor named world’s leading Type 1 Diabetes expert

The ranking was announced by Expertscape, an online knowledge base of worldwide biomedical expertise in many medical conditions, including type 1 diabetes
Sep 26, 2018 // Immune Matters

Q&A with Dr. Matthias von Herrath

Considered the top type 1 diabetes expert in the world, Matthias von Herrath, M.D., feels equally at home in academia and big pharma.

A latecomer to biomedical research, Dr. Matthias von Herrath is running an innovative and world-renowned research program on the pathology of type 1 and type 2 diabetes as part of the national Pancreatic Organ Donor network (nPOD) and spearheads Novo Nordisk's T1D research center in Seattle.

Mar 23, 2018 // Science Immunology

Bystander T cells can steal the show from "professional" regulatory cells in resolving inflammation

LJI researchers show that non-specific bystander T cells can play an active role in countering type 1 diabetes
Jun 11, 2014

La Jolla Institute scientist named World's #1 Expert in Juvenile Diabetes

von Herrath Lab


Clin Immunol.

IL-4R is expressed on alpha and beta cells of human pancreata.

Rajendran S, Graef M, Chu T, von Herrath M.
Trends Immunol

Regulatory immune mechanisms beyond regulatory T cells

Christoffersson G, von Herrath M

Loss of IDO1 expression from human pancreatic β-Cells precedes their destruction during the development of Type 1 Diabetes

Anquetil F, Mondanelli G, Gonzalez N, Rodriguez Calvo T, Zapardiel Gonzalo J, Krogvold L, Dahl-Jørgensen K, Van den…
Clin Immunol

OAS1 is not associated with MHC class I hyperexpression in the islets of donors with T1D regardless of disease duration

Sabouri S, Mikulski Z, von Herrath MG
Front Immunol

Distinct housing conditions reveal a major impact of adaptive immunity on the course of obesity-induced type 2 diabetes

Sbierski-Kind J, Kath J, Brachs S, Streitz M, von Herrath MG, Kühl AA, Schmidt-Bleek K, Mai K, Spranger J, Volk HD
Sci Immunol

Suppression of diabetes by accumulation of non-islet-specific CD8+ effector T cells in pancreatic islets

Christoffersson G, Chodaczek G, Ratliff SS, Coppieters K, von Herrath MG
BMC Immunol

Low HLA binding of diabetes-associated CD8+ T-cell epitopes is increased by post ranslational modifications

Sidney J, Vela JL, Friedrich D, Kolla R, von Herrath M, Wesley JD, Sette A
Cell Rep

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

Brissova M, Haliyur R, Saunders D, Shrestha S, Dai C, Blodgett DM, Bottino R, Campbell-Thompson M, Aramandla…
Acta Diabetol

The shifting paradigm of a "cure" for type 1 diabetes: is technology replacing immune based therapies?

Pettus J, von Herrath M
J Autoimmun

Anti-IL-21 monoclonal antibody combined with liraglutide effectively reverses established hyperglycemia in mouse models of type 1 diabetes

Rydén AK, Perdue NR, Pagni PP, Gibson CB, Ratliff SS, Kirk RK, Friesen TJ, Haase C, Coppieters K, von Herrath MG,…
Cell Metab

Antigen-specific peptide immunotherapy for type 1 diabetes: proof of safety, hope for efficacy

Coppieters K, von Herrath M
Nat Rev Endocrinol

β-Cell mass versus function in type 1 diabetes mellitus: truth or dare?

Rodriguez-Calvo T, Atkinson M, von Herrath M

Metabolically inactive insulin analogue does not prevent autoimmune diabetes in NOD mice

Gronholm J, Pagni PP, Pham MN, Gibson CB, Macomber PF, Vela JL, von Herrath M, Lenardo MJ
J Autoimmun

Alpha cells, the main source of IL-1β in human pancreas

Anquetil F, Sabouri S, Thivolet C, Rodriguez-Calvo T, Zapardiel-Gonzalo J, Amirian N, Schneider D, Castillo E,…
Diabetes Obes Metab

Immunohistochemical assessment of glucagon-like peptide 1 receptor (GLP-1R) expression in the pancreas of patients with type 2 diabetes

Kirk RK, Pyke C, von Herrath MG, Hasselby JP, Pedersen L, Mortensen PG, Knudsen LB, Coppieters K

Increase in pancreatic proinsulin and preservation of β-cell mass in autoantibody positive donors prior to type 1 diabetes onset

Rodriguez-Calvo T, Zapardiel-Gonzalo J, Amirian N, Castillo E, Lajevardi Y, Krogvold L, Dahl-Jørgensen K, von Herrath…

Re-addressing the 2013 consensus guidelines for the diagnosis of insulitis in human type 1 diabetes: is change necessary?

Campbell-Thompson ML, Atkinson MA, Butler AE, Giepmans BN, von Herrath MG, Hyöty H, Kay TW, Morgan NG, Powers AC,…
Cell Metab

Immunotherapy for type 1 diabetes: why do current protocols not halt the underlying disease process?

Kolb H, von Herrath M

Islet cell hyperexpression of HLA class I antigens: a defining feature in type 1 diabetes

Richardson SJ, Rodriguez-Calvo T, Gerling IC, Mathews CE, Kaddis JS, Russell MA, Zeissler M, Leete P, Krogvold L,…
Autoimmun Rev

The viral paradigm in type 1 diabetes: who are the main suspects?

Rodriguez-Calvo T, Sabouri S, Anquetil F, von Herrath MG
Eur J Immunol

CD40L expression by CD4+ but not CD8+ T cells regulates antiviral immune responses in acute LCMV infection in mice

Durlanik S, Loyal L, Stark R, Sercan Alp Ö, Hartung A, Radbruch A, von Herrath M, Matzmohr N, Frentsch M, Thiel A
Front Immunol

A deeper look into type 1 diabetes - imaging immune responses during onset of disease

Christoffersson G, von Herrath MG

A preclinical consortium approach for assessing the efficacy of combined anti-CD3 plus IL-1 blockade in reversing new-onset autoimmune diabetes in NOD mice

Gill RG, Pagni PP, Kufper T, Wasserfall CH, Deng S, Posgai A, Manenkova Y, Bel Hani A, Straub L, Bernstein P, Atkinson…
Clin Immunol

Oral insulin (human, murine, or porcine) does not prevent diabetes in the non-obese diabetic mouse

Pham MN, Gibson C, Rydén AK, Perdue N, Boursalian TE, Pangi PP, Coppieters K, Skonberg C, Porsgaard T, von Herrath M,…

Recent advances in understanding type 1 diabetes

Christoffersson G, Rodriguez-Calvo T, von Herrath M
Clin Exp Immunol

Factors impeding the discovery of an intervention-based treatment for type 1 diabetes

von Herrath MG, Korsgren O, Atkinson MA
Clin Exp Immunol

CD4 T cell differentiation in type 1 diabetes

Walker LS, von Herrath M
Journal of Histochemistry & Cytochemistry

Heterogenity and loblarity of pancreatic pathology in type 1 diabetes during the prediabetic phase

Rodriguez-Calvo T, Suwandi JS, Amirian N, Zapardiel-Gonzalo J, Anquetil F, Sabouri S, von Herrath MG
Diabetes Care

Current concepts on the pathogenesis of type 1 diabetes-considerations for attempts to prevent and reverse the disease

Atkinson MA, von Herrath M, Powers AC, Clare-Salzler M

Enterovirus infection and type 1 diabetes: closing in on a link?

Rodriguez-Calvo T, von Herrath MG
Journal of Autoimmunity

The Hsp60 peptide p77 enhances anti-CD3 mediated diabetes remission in non-obest diabetic mice

Sarikonda G, Sachithanantham S, Miller JF, Pangi PP, Coppieters KT, von Herrath M

Inflammation and hyperglycemia mediate Deaf1 splicing in pancreatic lymph nodes via distinct pathways during type 1 diabetes

Yip L, Fuhlbrigge R, Taylor C, Creusot RJ, Nishikawa-Matsumura T, Whiting CC, Schartner JM, Akter R, von Herrath M,…
Reviews in Medical Virology

Enteroviruses, hygiene and type 1 diabetes: toward a preventive vaccine

Drescher KM, von Herrath M, Tracy S
Journal of Autoimmunity

Beta-cell specific production of IL6 in conjunction with a mainly intracellular but not mainly surface viral protein causes diabetes

Van Belle TL, Pagni PP, Liao J, Sachithanantham S, Dave A, Bel Hani A, Manenkova Y, Amirian N, Yang C, Morin B, Zhang…

The type 1 diabetes signature: hardwired to trigger inflammation?

Coppieters KT, von Herrath MG

Increased immune cell infiltration of the exocrine pancreas: a possible contribution to the pathogenesis of type 1 diabetes

Rodriguez-Calvo T, Ekwall O, Amirian N, Zapardiel-Gonzalo J, von Herrath MG
PLoS One

BDC12-4.1 T-cell receptor transgenic insulin-specific CD4 T cells are resistant to in vitro differentiation into functional Foxp3+ T regulatory cells

Sarikonda G, Fousteri G, Sachithanantham S, Miller JF, Dave A, Juntti T, Coppieters KT, von Herrath M
Clinical Immunology

Higher proinflammatory cytokine production and spontaneous activation in some type 1 and type 2 diabetic subjects

Sarikonda G, Sachithanantham S, Pettus J, Rodriguez-Calvo T, Phatak S, Edelman S, von Herrath M

Potential viral pathogenic mechanism in human type 1 diabetes

Schneider DA, von Herrath MG
Clinical Immunology

Regulatory T cells control diabetes without compromising acute anti-viral defence

Baca Jones C, Pagni PP, Fousteri G, Sachithanantham S, Dave A, Rodriguez-Calvo T, Miller J, von Herrath MG
Proceedings of the National Academy of Sciences of the United States of America

CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients

Floyel T, Brorsson C, Nielsen LB, Miani M, Bang-Berthelsen CH, Friedrichsen M, Overgaard AJ, Berchtold LA, Wiberg A,…

Combination therapy with an anti-IL-1β and GAD65 DNA vaccine can reverse recent-onset diabetes in RIP-GP mouse model

Pagni PP, Bresson D, Rodriguez-Calvo T, Hani AB, Manekova Y, Amirian N, Blaszczak A, Faton S, Sachithanantham S, von…
Journal of Autoimmunity

CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes

Sarikonda G, Pettus J, Phatak S, Sachithanantham S, Miller JF, Wesley JD, Cadag E, Chae J, Ganesan L, Mallios R,…
PLoS One

Direct infection of dendritic cells during chronic viral infection suppresses antiviral T cell proliferation and induces IL-10 expression in CD4 T cells

Baca Jones C, Filippi C, Sachithanantham S, Rodriguez-Calvo T, Ehrhardt K, von Herrath M
Molecular Metabolism

Metabolic syndrome - removing roadbloacks to therapy: antigenic immunotherapies

Coppieters KT, von Herrath MG
Clinical Immunology

Trials in type 1 diabetes: antigen-specific therapies

Coppieters KT, Harrison LC, von Herrath MG
Clinical Immunology

Keeping the patient perspective: where are we in the world of type 1 diapetes?

Pettus J, von Herrath M
Clinical Immunology

Combination therapy with anti-CD6 and oral insulin immunisation reverses recent onset diabetes in non obese diabetic mice but fails to induce lasting tolerance

von Herrath MG
Journal of Immunology

Exogenous OX40 stimulation during lymphocytic choriomeningitis virus infection impairs follicular Th cell differentiation and diverts DC4 T cells into the effector lineage by upregulating blimp-1

Boettler T, Choi YS, Salek-Ardakani S, Cheng Y, Moeckel F, Croft M, Crotty S, von Herrath M

The diagnosis of insulitis in human type 1 diabetes

Campbell-Thompson ML, Akinson MA, Butler AE, Chapman NM, Frisk G, Gianani R, Giepmans BN, von Herrath MG, Hyoty H, Kay…
PLoS One

Temporal intra-individual variation of immunological biomarkers in type 1 diabetes patients: implications for future use in cross-sectional assessment

Sarikonda G, Pettus J, Sachithanantham S, Phatak S, Miller JF, Ganesan L, Chae J, Mallios R, Edelman S, Peters B, von…
Journal of Autoimmunity

The clinical and immunological significance of GAD-specific autoantibody and T-cell responses in type 1 diabetes

Boettler T, Pagni PP, Jaffe R, Cheng Y, Zerhouni P, von Herrath M

Functional redundancy of CXCR3/CXCL10 signaling in the recruitment of diabetogenic cytotoxic T lymphocytes to pancreatic islets in a virally induced autoimmune diabetes model

Coppieters KT, Amirian N, Pangi PP, Jones CB, Wiberg A, Lasch S, Hintermann E, Christen U, von Herrath MG
Diabetes Obesity & Metabolism

Emerging immune therapies in type 1 diabetes and pancreatic islet transplantation

Schneider DA, Kretowicz AM, von Herrath MG
PLoS One

Transient B-cell depletion with anti-CD20 in combination with proinsulin DNA vaccine or oral insulin: immunologic effects and efficacy in NOD mice

Sarikonda G, Sachithanantham S, Manenkova Y, Kupfer T, Posgai A, Wasserfall C, Bernstein P, Straub L, Pagni PP,…
Science Translational Medicine

Plasmid-encoded proinsulin preserves C-peptide while specifically reducing proinsulin-specific CD8+ T cells in type 1 diabetes

Roep BO, Solvason N, Gottlieb PA, Abreu JR, Harrison LC, Eisenbarth GS, Yu L, Leviten M, Hagoplan WA, Buse JB, von…
Journal of Pathology

Antibody cross-reactivity and the viral aetiology of type 1 diabetes

Coppieters KT, von Herrath M
Clinical and Experimental Immunology

Progress in immune-based therapies for type 1 diabetes

von Herrath M, Peakman M, Roep B
Journal of Autoimmunity

NKG2D blockade facilitates diabetes prevention by antigen-specific Tregs in a virus-induced model of diabetes

Van Belle TL, Ling E, Haase C, Bresson D, Ursø B, von Herrath MG
PLoS One

Blockade but not overexpression of the junctional adhesion molecule C influences virus-induced type 1 diabetes in mice

Christen S, Coppieters K, Rose K, Holdener M, Bayer MM, Pfeilschifter JM, Hintermann E, von Herrath MG, Aurrand-Lions…
ACTA Pathologica Microbiologica Et Immunologica Scandinavica

Viral infections and molecular mimicry in type 1 diabetes

Coppieters KT, Wilberg A, von Herrath MG
PLoS Pathogens

OX40 facilitates control of a persistent virus infection

Boettler T, Moeckel F, Cheng Y, Heeg M, Salek-Ardakani S, Crotty S, Croft M, von Herrath MG
Therapeutic Archives

Introduction to preventative and predictive medicine: past experience and future reality

Suchkov SV, Rose N, Notkins A, Golubnichaia O, von Herrath M, Legg M, Marshall T
Proceedings of the National Academy of Sciences of the United States of America

IL-7 receptor α blockade, an off-switch for autoreactive T cells

Boettler T, von Herrath M

The microbiology of human hygiene and its impact on type 1 diabetes

Chapman NM, Coppieters K, von Herrath M, Tracy S
Current Opinion in Rheumatology

Infection as a cause of type 1 diabetes?

Christen U, Bender C, von Herrath MG
Viral Immunology

TGF-β blockade does not improve control of an established persistent viral infection

Boettler T, Cheng Y, Ehrhardt K, von Herrath M

Preexisting autoantibodies predict efficacy of oral insulin to cure autoimmune diabets in combination with anti-CD3

Mamchak AA, Manenkova Y, Leconet W, Zheng Y, Chang JR, Stokes CL, Shoda LK, von Herrath M, Bresson D

Interleukin-21 receptor-mediated signals control autoreactive T cell infiltration in pancreatic islets

Van Belle TL, Nierkens S, Arens R, von Herrath MG

Following the fate of one insulin-reactive CD4 T cell: conversion into teffs and tregs in the periphery controls deiabetes in NOD mice

Fousteri G, Jasinski J, Dave A, Nakayama M, Pagni P, Lambolez F, Juntti T, Sarikonda G, Cheng Y, Croft M, Cheroutre H,…
Clinical and Experimental Immunology

Immunology in the clinic review series: focus on type 1 diabetes and viruses: the role of viruses in type 1 diabetes: a difficult dilemma

Coppieters KT, Wiberg A, Tracy SM, von Herrath MG
Expert Review of Anti-infective Therapy

Can an immune-regulatory vaccine prevent HIV infection?

Boettler T, Cunha-Neto E, Kalil J, von Herrath M
Clinical Immunology

Combination therapy with InsB9-23 peptide immunization and CTLA4-IgG does not reverse diabetes in NOD mice

Schneider DA, Sarikonda G, von Herrath MG
Nature Immunology

Motifs for a deadly encounter

Coppieters KT, von Herrath MG
Nature Medicine

Unraveling the autoimmune translational research process layer by layer

Blumberg RS, Dittel B, Halfer D, von Herrath M, Nestle FO
Journal of Clinical Investigation

Intravital imaging of CTLS killing islet cells in diabetic mice

Coppieters KT, Amirian N, von Herrath M
Cold Spring Harbor Perspectives in Medicine

Virus infectons in type 1 diabetes

Coppieters KT, Boettler T, von Herrath M
Journal of Experimental Medicine

Demonstration of islet-autoreactive CD8 T cells I insulitic lesions from recent onset and long-term type 1 diabetes

Coppieters KT, Dotta F, Amirian N, Campbell PD, Kay TW, Atkinson MA, Roep BO, von Herrath MG
Journal of Autoimmunity

Antigen-specific prevention of type 1 diabetes in NOD mice is ameliorated by OX40 agonist treatment

Bresson D, Fousteri G, Manenkova Y, Croft M, von Herrath M
Diabetes/Metabolism Research and Reveiws

Persistent glucose transporter expression on pancreatic beta cells from longstanding type 1 diabetes individuals

Coppieters KT, Wiberg A, Amirian N, Kay TW, von Herrath MG
Clinical Reveiws in Allergy & Immunology

Viruses and cytotoxic T lymphocytes in type 1 diabetes

Coppieters KT, von Herrath MG
Methods in Molecular Biology

Immunosuppressive mechanisms during viral infectious diseases

Sarikonda G, von Herrath MG
Journal of Immunology

Development of autoimmune diabetes in the absence of detectable IL-17A in a CD8-driven virall induced model

Van Belle TL, Esplugues E, Liao J, Juntti T, Flavell RA, von Herrath MG
Journal of Medical Virology

How viral infections enhance or prevent type 1 diabetes-from mouse to man

von Herrath M, Filippi C, Coppieters K
Clinical and Experimental Immunology

Incidental CD8 T cell reactivity against caspase-cleaved apoptotic self-antigens from ubiquitously expressed proteins in islets from pediabetic human leucocyte antigen-A2 transgenic non-obese diabetic mice

Coppieters KT, Amirian N, von Herrath MG
Current Opinion in Endocrinology, Diabetes and Obesity

2011 Update: antigen-specific therapy in type 1 diabetes

Michels AW, von Herrath MG
Journal of Autoimmunity

Nasal cardiac myosin peptide treatment and OX40 blockade protect mice from acute and chronic virally-induced myocarditis

Fousteri G, Dave A, Morin B, Omid S, Croft M, von Herrath MG

How does type 1 diabetes develop?: The notion of homicide or β-cell suicide revisited

Atkinson MA, Bluestone JA, Eisenbarth GS, Hebrok M, Herold KC, Accili D, Peitropaolo M, Arvan PR, von Herrath M, Markel…
Cellular & Molecular Immunology

Do viral infections protect from or enhance type 1 diabetes and how can we tell the difference?

Christen U, von Herrath MG
European Journal of Immunology

TLR2 signaling improves immunoregulation to prevent type 1 diabetes

Filippi CM, Ehrhardt K, Estes EA, Larsson P, Oldham JE, von Herrath MG
Journal of Experimental Medicine

Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay

Diana J, Brezar V, Beaudoin L, Dalod M,Mellor A, Tafuri A, von Herrath M, Boitard C, Mallone R, Lehuen A
Clinical and Experimental Immunology

Anti-thymoglobulin (ATG) treatment does not reverse type 1 diabetes in the acute virally induced rat insulin promoter-lymphocytic choriomeningitis virus (RIP-LCMV) model

Bresson D, von Herrath MG
Science Translational Medicine

Humanizing animal models: a key to autoimmune diabetes treatement

Bresson D, von Herrath M
Human Vaccines

Type 1 diabetes vaccine development: animal models vs. humans

Boettler T, von Herrath M
Expert Review of Clinical Immunology

Protection against or triggering of Type 1 diabetes? Different roles for viral infections

Boettler T, von Herrath M
Seminars in Immunopathology

Beta cells under attack: toward a better understanding of type 1 diabetes immunopathology

Coppieters KT, Roep BO, von Herrath MG
PLoS One

Increased memory conversion of naïve CD8 T cells activated during late phases of acute virus infection due to decreased cumulative antigen exposure

Fousteri G, Dave A, Juedes A, Juntti T, Morin B, Togher L, Farber DL, von Herrath M
Physiological Reviews

Type 1 diabetes: etiology, immunology, and therapeutic strategies

Van Belle TL, Coppieters KT, von Herrath MGVan Belle TL, Coppieters KT, von Herrath MG
Int Immunopharmacol

Immunotherapy of type 1 diabetes - how to rationally priotize combination therapies in T1D

Boettler T, von Herrath MG
PLoS One

A novel technique for the in vivo imaging of autoimmune diabetes development in the pancras by two-photon microscopy

Coppieters K, Martinic MM, Kiosses WB, Amirian N, von Herrath MG

Virtual optimization of nasal insulin therapy predicts immunization frequency to be crucial for diabetes protection

Fousteri G, Chan JR, Zheng Y, Whiting C, Dave A, Bresson D, Croft M, von Herrath M
J Autoimmun

Expression level of a pancreatic neo-antigen in beta cells determines degree of diabetes pathogenesis

Martinic MM, Huber C, Coppieters K, Oldham JE, Gavin AL, von Herrath MG

Subcutaneous insulin B:9-23/IFA immunisation induces Tregs that control late-stage prediabetes in NOD mice through IL-10 and INFgamma

Fousteri G, Dave A, Bot A, Juntti T, Omid S, von Herrath MG

Antigen-specific immuotherapy for type 1 diabetes: maximizing the potentia

Peakman M, von Herrath MG

Dimorphic histopathology of long-standing childhood-onset diabetes

Gianani R, Campbell-Thompson M, Sarkar SA, Wasserfall C, Pulgiese A, Solis JM, Kent SC, Hering BJ, West E, Steck A,…
Viral Immunol

Miminal effect of CD103 expression on the control of a chronic antiviral immune response

Fousteri G, Dave A, Juntti T, Morin B, McClure M, von Herrath MG
J Immunol

Essential role for TLR9 in prime but not prime-boost plasmid DNA vaccination to activate dendritic cells and protect from lethal viral infection

Rottembourg D, Filippi CM, Bressosn D, Ehrhardt K, Estes EA, Oldham JE, von Herrath MG
J Autoimmun

Pre-existing autoimmunity determines type 1 diabetes outcome after Flt3-ligand treatment

Van Belle TL, Juntti T, Liao J, von Herrath MG
Clin Exp Immunol

Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN-JDRF Type 1 Giabetes Combination Therapy Assessment Group

Matthews JB, Staeva TP, Berstein PL, Peakman M, von Herrath MG

Combination therapies for type 1 diabetes: why not now

von Herrath MG
Clin Exp Immunol

99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: viruses, autoimmunity and immunogregulation

Filippi CM, von Herrath MG
Mol Ther

Genetic-induced variatons in the GAD65 T cell repetoire governs efficacy of anti-CD3/GAD65 combination therapy in new-onset type 1 diabetes

Bresson D, Fradkin M, Manenkova Y, Rottembourg D, von Herrath MG
J Autoimmun

Viral triggers for autoimmunity: is the glass of molecular mimicry half full or half empty

Christen U, Hintermann E, von Herrath MG
Cell Transplant

Pancreatic tissue transplanted in TheraCyteTM encapsulation devices is protected and prevents hyperglycemia in a mouse model of immune-mediated diabetes

Boettler T, Schneider D, Cheng Y, Kadoya K, Brandon EP, Martinson L, von Herrath M

Principal Investigator

Matthias von Herrath, M.D.


Dr. von Herrath serves as Director of the Center for Type 1 Diabetes Research in addition to being a full Professor in the La Jolla Institute for Immunology. Dr. von Herrath’s research focuses on strategies to prevent type 1 diabetes through the induction of regulatory T cells.

Dr. von Herrath wrote his thesis in the field of Biochemistry and then received his M.D. in Medicine from the Freiburg Medical School in Freiburg, Germany in 1988. He did his residency work at the Freiburg Medical Center in the Internal Medicine/Immunology department and at the Diakonic Hospital’s Intensive Care Unit in Freiburg. For his postdoctoral work, Dr. von Herrath went to The Scripps Research Institute and worked in its Neuropharmacology and Immunology departments.

Dr. von Herrath is an editor and reviewer for numerous publications as well as being a member of the American Society of Clinical Investigator and a Council Member for the International Diabetes Society. In addition, he is an Adjunct Professor of Medicine at the University of California, San Diego. He is the recipient of the 2008 American Diabetes Association-Lilly Outstanding Scientist Achievements Award, the 2006 Grotzky Award from the Juvenile Diabetes Foundation International, the 2007-2012 Scholar Award from the Juvenile Diabetes Foundation, awarded the 2014 Langerhans-Preis – German Diabetes Foundation, and was ranked in 2014 as the #1 Juvenile Diabetes Expert by “Expertscape.”

Lab Members

Gabriela Aguila

Research Technician I

Since 2001 I was an animal care technician and now, for the last year and a half, I maintain the colony for our Type 1 Diabetes lab and assist with the research. Also I am a local and national member of AALAS (American Association for Laboratory Animal Science) where I am an active participant in outreach programs to further education in research.

Completed an Associate in science in Biotechnology at Southwestern College and currently working on an Associate in science in Biology. I look forward to completing my Bachelors and Masters programs so that one day I may also teach.

Christine Bender, Ph.D.

Postdoctoral Fellow

Christine Bender, Ph.D. graduated from the University of Applied Sciences Mannheim, Germany in 2010 with a Master of Science degree in Biotechnology. She finished her thesis focusing on glutamic acid decarboxylase (GAD) autoantibody affinity in schoolchildren in the Institute of Diabetes Research in Munich. Before joining Prof. Matthias von Herrath’s group, she obtained her Ph.D. in Biological Sciences at the University Frankfurt am Main, Germany in 2016. Her thesis work focused on islet transplantation using the RIP-LCMV mouse model for Type 1 Diabetes and was performed in the laboratory of Prof. Urs Christen, Dept of Pharmacology and Toxicology at the Goethe University Hospital Frankfurt. Thereafter, Dr. Bender began working as a postdoctoral fellow in the group of Prof. Matthias von Herrath at the La Jolla Institute for Immunology in March of 2017.

Research Focus:
Her long-standing interest has been in Type 1 Diabetes development, prevention and investigating novel treatment therapies. Type 1 diabetes, is a serious and challenging disease which affects millions of people worldwide. It is an autoimmune disease, which develops when immune cells mistakenly attack and destroy the body’s own insulin-producing beta cells in the pancreas. The autoimmune attack is driven by T cells, which play an important role in orchestrating the functions of the immune system. The prime candidates for wreaking havoc in the pancreas are CD8 T cells. Therefore, her major project is to study antigen-specific CD8 T cells, in pancreas from donors with type 1 diabetes and healthy donors. Human pancreas tissues obtained from the Network for Pancreatic Organ Donors with Diabetes (nPOD) will be analyzed using immunostaining applications to detect the total number of these cells, their location in the pancreas and their exact characteristics of antigen-specific CD8 T cells in disease progression. The overall goal is to improve our understanding of the role of antigen-specific CD8 T cells in the disease before and after diagnosis. And finally, to provide an opportunity to intervene and stop this immune response from happening and prevent type 1 diabetes.

Career Goals:
She plans to pursue a career in scientific research primarily focused on human type 1 diabetes.

Mehdi Ayech Benkahla, Ph.D.

Postdoc Fellow (0 year)

Bio sketch :
I graduated from the Faculty of Sciences of Tunis, Tunisia in 2012 with a Master of Science degree in Microbiology. Then, i was awarded an Erasmus Mundus Ph.D. scholarship to study at the University of Lille, France from which i graduated with a Ph.D. in Virology. I joined the group of Prof. Matthias von Herrath at the La Jolla Institute for Immunology in July 2018.

Research project :
My long-standing interest is the viral pathogenesis of type 1 diabetes (T1D). T1D is an autoimmune disorder of unknown etiology that damages the insulin-producing beta cells in the pancreatic islets. The disease pathogenesis is the result of a complex interaction between genetic, immune and environmental factors. Among the potential environmental factors, viral infections arise as critical triggers for type 1 diabetes development. My project is to study the impact of viral infections on human pancreatic tissues obtained from the Network for Pancreatic Organ Donors (nPOD).

Career goals :
Pursuing a career in scientific research in industry.

Ericka Castillo

Research Technician I

Completed Biotechnology program at Southwestern College in 2014. Interned at The Scripps Research Institute the summer of 2014. Started working in the von Herrath lab in October of 2014 as a lab assistant and got promoted to lab technician in 2015.

Along with general maintenance of the lab, I am involved in various contract projects from Novo Nordisk. I also assist with immunohistology stainings and data organization in association with various postdocs, who work with pancreas samples from nPOD.

Tiffany Chu

Lab assistant

I currently study at UCSD with a planned B.S. in Molecular Biology and minor in Spanish Linguistics. I joined the von Herrath laboratory in January 2018. In addition to general lab technician duties, I assist with Novo Nordisk projects as well as work with postdoctorates in immunohistology staining and data analysis.

Natalie von Herrath

Research Technician II

I graduated from University of California, Los Angeles with a Bachelor of Science in Biology in 2008. Short after graduation I moved to San Diego to obtain some experience in the field of research before I start my graduate degree in Pharmacology. I started working in von Herrath Lab under Ken Koppieters supervision as a research technician. Later, I started working with Teresa Rodrigues on histopathology of type 1 diabetes using human pancreas tissues donated via nPOD (Network for Pancreatic Organ Donors with Diabetes) to better understand the function of immune cells. Working in the field of immunology specially Type 1 diabetes has been both rewarding and challenging in the same time. My hope is that one day there will be a cure for type 1 diabetes.

Jessica Jang

Intern (non-paid)

Mason Lee

Intern (non-paid)

Sumana Mahata

Graduate Student

Estefania Quesada Masachs, M.D., Ph.D.

Postdoctoral Fellow

I obtained my MD degree at University of Barcelona (UB) in 2008. I finished my residency in Rheumatology and a 2-year training program in Pediatric Rheumatology at Vall d’Hebron University Hospital. During the early stages of my career I got fascinated by biomedical research and hence I’ve got involved in multiple clinical research projects and clinical trials. I also did a fellowship at Istituto Giannina Gaslini in Italy, Center of Excellence in Pediatric Rheumatology according to the European League Against Rheumatism (EULAR). In 2017, I obtained my PhD at the Autonomous University of Barcelona (UAB) cum laude and the mention as an international doctor. My PhD thesis was focused on identifying immunological differences in relation to age and treatment in patients with Juvenile Idiopathic Arthritis. I joined Prof. von Herrath’s lab as a postdoctoral fellow at La Jolla Institute for Immunology in 2018.

Research Focus:
Currently, I am working on type 1 diabetes, investigating the role of different immune cells, cytokines and other signaling molecules in disease initiation and progression. I analyze human pancreas tissues obtained from the Network for Pancreatic Organ Donors with Diabetes (nPOD) using immunostaining techniques and I also work in animal models. I am particularly interested in gaining insight in the processes occurring in autoimmune diseases that start in childhood.

Career Goals:
I plan to pursue a career as a physician-scientist focusing my research in translational immunology for human autoimmune diseases.

Susanne Pfeiffer

Postdoc Fellow (0 year)

Matthew Soldano


Samuel Zilberman

Intern (non-paid)

von Herrath Lab

Research Projects

Specificity of Pancreatic CD8 T Cells in Human Type 1 Diabetes

Teresa Rodriguez-Calvo
A better understanding of how type 1 diabetes (T1D) develops is the first step to potentially develop new therapies capable of preventing or permanently reversing the disease. Due to the inaccessibility to human pancreatic tissue, our knowledge of the disease in humans is limited. Although mouse models have been a very useful tool for the past 30 years, humans show different islet architecture and islet cell distribution compared to rodent islets. These differences might have impacted therapeutic outcomes, which worked well in mouse models but frequently do not translate to humans, and might explain why developing efficient new therapies has been challenging.

More recently, autopsy studies of pancreas samples obtained from a limited number of individuals with T1D have challenged longstanding dogmas of how T1D develops. The Network for Pancreatic Organ donors with Diabetes (nPOD) was established with the idea of providing valuable tissues from healthy and diabetic donors in order to answer basic questions about the pathogenesis of T1D. Thanks to the nPOD program, we can study the pancreas, spleen and lymph nodes from donors with T1D in order to determine if the T cells identified in mouse models (T cells reactive against beta cell proteins or autoreactive T cells) are the same cells that destroy beta cells in human T1D and what their distribution and activation status is in the pancreas and in other tissues. I am also interested in the possible role of viral infections and whether they could make islets more accessible for these destructive, autoreactive T cells or vice versa.

Characterization of beta cell mass and function during the pre-diabetic phase

Teresa Rodriguez-Calvo
In 1986 Prof. George Eisenbarth proposed a model of disease progression that postulated a linear beta cell mass decay during the pre-diabetic phase. However, genetic factors and environmental triggers like viral infections are likely to contribute to fluctuations in beta cell mass before disease onset. Therefore, a nonlinear model depicting T1D as a “relapsing-remitting” disease has also been proposed. In addition, it has recently been shown that beta cell destruction and metabolic dysfunction are events closely associated with disease onset. Importantly, recent studies have demonstrated that during the prediabetic phase there are detectable episodes of beta cell dysfunction and killing that culminate in a peak in beta cell death before the onset of disease.

Autoantibody positive individuals might offer insight into the early events underlying diabetes development. I am investigating potential changes in beta cell mass in the pancreas of non-diabetic autoantibody positive individuals, in order to compare them to healthy, non-diabetic donors. Our findings could potentially show how beta cells change in early stages of the disease and if there is an alteration of the insulin ratio that could indicate a defect on their function.

Role of HHV-6 in the pathogenesis of Type 1 Diabetes

Somayeh Sabouri
Type 1 diabetes (T1D) is an autoimmune disease causing the destruction of insulin-producing beta cells in the pancreatic islets. Immunopathogenesis of T1D is still unknown. There are lines of evidence suggesting that both environmental factors such as viruses and genetic susceptibility play an important role in triggering the disease. However, there is still no direct link between viral infection and T1D.

Human herpesvirus 6 (HHV-6) is a ubiquitous pathogen of the beta-herpesvirus family. It has been proposed that HHV-6 plays a role in several autoimmune disorders such as multiple sclerosis, autoimmune connective tissue diseases, and Hashimoto’s thyroiditis. However, little is known about the involvement of HHV-6 infection in the pathogenesis of T1D. GlycoproteinB (gpB) is conserved in all herpesviruses and is known for playing a critical role during the membrane fusion and viral infection. To explore the role of HHV-6 in the pathogenesis of T1D, we obtained pancreatic tissue sections from T1D, autoantibody positive, and non-diabetic donors provided by the Network for Pancreatic Organ Donors with Diabetes (nPOD). The presence of HHV-6 gpB will be analyzed at the protein level by indirect immunofluorescence.

This study will allow us to identify the virally infected cells within the pancreas in order to define a potential mechanism of action of the virus at the cellular level. Furthermore, the correlation between gpB and MHC-I expression, a hallmark in early T1D, will be elucidated within the pancreas of the pre-diabetic and diabetic patients. Here we speculate that herpesvirus infection might be a contributing factor to T1D pathogenesis. In combination with genetic susceptibility, the strength of the cellular and humoral immune response to virus infection might contribute to autoimmunity. This study will help to determine a possible role of herpersviruses in the immunopathogenesis of T1D which can lead to preventative measures for future clinical trials.

IDO1 and IL-6 expression in pancreatic islets from diabetic subjects as a biomarker for T1D patients

Florence Anquetil
Indoleamine 2,3-dioxygenase 1 (IDO1) is a metabolic enzyme catalyzing the conversion of tryptophan into kynurenines, whose catalytic and non-catalytic effects are involved in the regulation of immunity and in autoimmune diseases. Cytokines are a key modulator of the expression of IDO1: interferon-γ upregulates the enzyme in dendritic cells whereas interleukin 6 (IL-6) promotes proteasomal degradation of IDO1. Current data show that most of children with type 1 diabetes (T1D) have a genetic or postranslational defect in IDO1 expression and activity in peripheral blood mononuclear cells (PBMCs). Interestingly, this phenotype can be corrected by incubation of PBMCs with tocilizumab, a licensed IL-6 receptor blocker. The same drug may also control hyperglycemia in non-obese diabetic mice with overt diabetes. Therefore, a subset of individuals with T1D may gain clinical benefit in restoring IDO1 immunoregulatory mechanisms by treatment with tocilizumab.
I aim at verifying whether the phenotype identified in PBMCs may also be demonstrated in pancreata by using tissue specimens obtainable from the network of Pancreatic Organ Donors. If the results confirms our hypothesis, this study could lead to a new course of treatment in T1D.

Phenotype of Pancreatic CD8 T Cells in Human Type 1 Diabetes

Florence Anquetil
Type 1 diabetes (T1D) is one of the most common chronic diseases of childhood in which insulin producing-cells are targeted by the immune system, leading to their destruction mainly by T cells, However, only limited data are available on the phenotype of the T cell implicated in the destruction process through the course of T1D.

For a long time, the study of human diabetic pancreata has been challenging due to a scarce access to the target organ. Recently, the Network for Pancreatic Organ donors with Diabetes (nPOD) was founded for the purpose of obtaining tissues from organ donors and has created a new opportunity to study the pathogenesis of T1D and better understand the local tissue environment.

This project will allows to determine the specific subsets of T cells present in pancreata from donors with T1D, pre-diabetic or control donors and provide the first detailed mapping of T cells in T1D .

In situ expression of IL-1beta in pancreas from diabetic patients

Somayeh Sabouri and Florence Anquetil
Type 1 diabetes (T1D) is an autoimmune disease that is characterized by the progressive loss of beta cells. During the last 30 years, intense efforts have been made to understand the role of cytokines in the pathogenesis of T1D. IL-1β has emerged as an interesting candidate due to its modulating effects on innate and adaptive immune responses and its role in promoting beta cell dysfunction and apoptosis in vitro.
However, recent trials using targeted IL-1 blockade in patients with T1D have failed to provide benefit and a trial in patients with Type 2 Diabetes (T2D) provided only limited benefits.

Thus, the role of IL-1 in diabetes pathogenesis is not clear and we aim at re-evaluating the presence of IL-1β in human pancreas in a systematic manner.

Trafficking and suppression by regulatory T cells in situ during onset of type 1 diabetes

Gustaf Christoffersson
Regulatory T cells and their actions have been extensively studied over decades in various models of autoimmunity. Harnessing the immune-regulatory properties of these cells has been the aim of many a venture on the translational end of autoimmune research. To this day, no major breakthrough has been made using these cells for cell-based therapies. In this project, we use a broad definition of “Tregs”, and investigate immune regulation performed by ‘non-conventional’ Tregs (we could also call them inducible or situation-dependent Tregs). Their function during autoimmunity is poorly understood, and detailed information on actions and true identity of these cells are lacking.

To study these events we apply both macroscopic and microscopic views on Treg trafficking and actions. Using the lab’s established method for intravital multiphoton imaging of the pancreas, high-resolved information on their behavior in the islet inflammation is gained. A whole-animal view of the trafficking and expansion of these immune cell subsets are achieved by multicolor flow cytometry in innovative fluorescent reporter strains. This two-pronged approach will enable us to get a broader picture of the immune regulation at play during type 1 diabetes.

Antigen specificity in CD8+ T cell infiltration, killing, and suppression at the pancreatic islets

Gustaf Christoffersson
Among the CD8+ cytotoxic T lymphocytes (CTL) found at inflamed islets in the pancreata of diabetic patients, very few are specific to antigens expressed in the islet. Very little is known about the activation, recruitment, or function of these non-specific cells. They are generally thought to add to islet damage through release of cytokines, but immune-suppressive effects from the presence of bystander CTLs have been described in other models.

Using well-defined antigen-driven models of type 1 diabetes, and state-of-the-art intravital multiphoton imaging, we are assessing CTL trafficking and actions. We are also mapping the phenotypes of CTLs present at islets in with regard to their expression of activation/suppression markers, and their secretome. We will also assess the islet microenvironment for metabolic and nutritional changes induced by bystander accumulation. Mapping the actions of both drivers and bystanders in type 1 diabetes is key to understanding the course of this disease. Insights into novel regulatory mechanisms during autoimmunity will increase the number of cellular tools available for modulating the autoimmune disease progression.

Neuro-immune crosstalk in the pancreas during onset of type 1 diabetes

Gustaf Christoffersson
The histopathologic features of human type 1 diabetes are remarkably heterogeneous throughout the pancreas. One lobule of the organ can appear completely unaffected by the ongoing autoimmune disease, while the neighboring lobule is lacking any sign of an insulin producing beta cell. The reasons for this pattern may be several, including viral or bacterial infection, anatomical features, or neuronal influence.

In an enigmatic disease such as type 1 diabetes, we are now looking into paths less treaded upon to try to find the underlying mechanisms to the disease. Neuronal input has been shown to have great impact on immune cell function in other autoimmune disorders such as multiple sclerosis. The neuronal influence in the onset of type 1 diabetes is investigated in this project, where nerve input to the pancreas is modulated in several ways. The effect on diabetes onset and progression is followed, and possible behavioral changes in immune cell subsets are monitored by intravital multiphoton microscopy of the pancreas.

Diabetes neuro-(auto)immune modulation

Enrique Montero
Autoreactivity to a set of self-components are present in the immune repertoire of healthy individuals, which may later develop autoimmune diseases. Type 1 Diabetes (T1D) is a prototype autoimmune disease, consequence of the insulin-producing islet ß-cells destruction by antigen-specific T-cells trafficking to the pancreas. However, neuro-immune networks may contribute to this process. Therefore, we are exploring whether nervous system antigen-reactive T-cells may modulate T1D pathogenesis. Potential dynamic cross-interference would help further understanding the layer of complexity integrating immune regulatory mechanisms governing the onset and progression of autoimmune diseases, and eventually devising novel therapeutic approaches.