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
Division of Developmental Immunology

Overview

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

Jun 11, 2014

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

von Herrath Lab

Publications

Cell Transplant

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

2016-03
Boettler T, Schneider D, Cheng Y, Kadoya K, Brandon EP, Martinson L, von Herrath M
Clin Immunol

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

2016-03
F1000Res

Recent advances in understanding type 1 diabetes

2016-01
Christoffersson G, Rodriguez-Calvo T, von Herrath M
Clin Exp Immunol

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

2016-01
von Herrath MG, Korsgren O, Atkinson MA
Clin Exp Immunol

CD4 T cell differentiation in type 1 diabetes

2016-01
Walker LS, von Herrath M
Diabetes

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

2015-12
Gill RG, Pagni PP, Kufper T, Wasserfall CH, Deng S, Posgai A, Manenkova Y, Hani AB, Straub L, Bernstein P, Atkinson MA,…
Journal of Histochemistry & Cytochemistry

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

2015-08
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

2015-06
Atkinson MA, von Herrath M, Powers AC, Clare-Salzler M
Diabetes

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

2015-05
Rodriguez-Calvo T, von Herrath MG
Journal of Autoimmunity

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

2015-05
Sarikonda G, Sachithanantham S, Miller JF, Pangi PP, Coppieters KT, von Herrath M
Diabetes

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

2015-02
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

2015-01
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

2014-12
Van Belle TL, Pagni PP, Liao J, Sachithanantham S, Dave A, Bel Hani A, Manenkova Y, Amirian N, Yang C, Morin B, Zhang…
Diabetes

The type 1 diabetes signature: hardwired to trigger inflammation?

2014-11
Coppieters KT, von Herrath MG
Diabetes

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

2014-11
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

2014-11
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

2014-11
Sarikonda G, Sachithanantham S, Pettus J, Rodriguez-Calvo T, Phatak S, Edelman S, von Herrath M
Diabetologia

Potential viral pathogenic mechanism in human type 1 diabetes

2014-10
Schneider DA, von Herrath MG
Clinical Immunology

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

2014-08
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

2014-07
Floyel T, Brorsson C, Nielsen LB, Miani M, Bang-Berthelsen CH, Friedrichsen M, Overgaard AJ, Berchtold LA, Wiberg A,…
Diabetes

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

2014-06
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

2014-05
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

2014-03
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

2014-01
Coppieters KT, von Herrath MG
Clinical Immunology

Trials in type 1 diabetes: antigen-specific therapies

2013-12
Coppieters KT, Harrison LC, von Herrath MG
Clinical Immunology

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

2013-12
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

2013-12
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

2013-11
Boettler T, Choi YS, Salek-Ardakani S, Cheng Y, Moeckel F, Croft M, Crotty S, von Herrath M
Diabetologia

The diagnosis of insulitis in human type 1 diabetes

2013-11
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

2013-11
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

2013-08
Boettler T, Pagni PP, Jaffe R, Cheng Y, Zerhouni P, von Herrath M
Diabetes

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

2013-07
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

2013-07
Schneider DA, Kretowicz AM, von Herrath MG
Science Translational Medicine

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

2013-06
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

2013-05
Coppieters KT, von Herrath M
Clinical and Experimental Immunology

Progress in immune-based therapies for type 1 diabetes

2013-05
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

2013-02
Van Belle TL, Ling E, Haase C, Bresson D, Ursø B, von Herrath MG
ACTA Pathologica Microbiologica Et Immunologica Scandinavica

Viral infections and molecular mimicry in type 1 diabetes

2012-12
Coppieters KT, Wilberg A, von Herrath MG
PLoS Pathogens

OX40 facilitates control of a persistent virus infection

2012-09
Boettler T, Moeckel F, Cheng Y, Heeg M, Salek-Ardakani S, Crotty S, Croft M, von Herrath MG
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

2012-07
Boettler T, von Herrath M
Islets

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

2012-07
Chapman NM, Coppieters K, von Herrath M, Tracy S
Current Opinion in Rheumatology

Infection as a cause of type 1 diabetes?

2012-07
Christen U, Bender C, von Herrath MG
Viral Immunology

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

2012-06
Boettler T, Cheng Y, Ehrhardt K, von Herrath M
Diabetes

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

2012-06
Mamchak AA, Manenkova Y, Leconet W, Zheng Y, Chang JR, Stokes CL, Shoda LK, von Herrath M, Bresson D
Immunity

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

2012-06
Van Belle TL, Nierkens S, Arens R, von Herrath MG
Diabetes

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

2012-05
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

2012-04
Coppieters KT, Wiberg A, Tracy SM, von Herrath MG
Expert Review of Anti-infective Therapy

Can an immune-regulatory vaccine prevent HIV infection?

2012-03
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

2012-03
Schneider DA, Sarikonda G, von Herrath MG
Nature Immunology

Motifs for a deadly encounter

2012-02
Coppieters KT, von Herrath MG
Nature Medicine

Unraveling the autoimmune translational research process layer by layer

2012-01
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

2012-01
Coppieters KT, Amirian N, von Herrath M
Cold Spring Harbor Perspectives in Medicine

Virus infectons in type 1 diabetes

2012-01
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

2012-01
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

2011-12
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

2011-11
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

2011-10
Coppieters KT, von Herrath MG
Journal of Immunology

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

2011-09
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

2011-09
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

2011-08
Coppieters KT, Amirian N, von Herrath MG
Current Opinion in Endocrinology, Diabetes and Obesity

2011 Update: antigen-specific therapy in type 1 diabetes

2011-08
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

2011-05
Fousteri G, Dave A, Morin B, Omid S, Croft M, von Herrath MG
Diabetes

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

2011-05
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?

2011-05
Christen U, von Herrath MG
European Journal of Immunology

TLR2 signaling improves immunoregulation to prevent type 1 diabetes

2011-05
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

2011-04
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

2011-03
Bresson D, von Herrath MG
Science Translational Medicine

Humanizing animal models: a key to autoimmune diabetes treatement

2011-02
Bresson D, von Herrath M
Human Vaccines

Type 1 diabetes vaccine development: animal models vs. humans

2011-01
Boettler T, von Herrath M
Expert Review of Clinical Immunology

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

2011-01
Boettler T, von Herrath M
Seminars in Immunopathology

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

2011-01
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

2011-01
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

2011-01
Van Belle TL, Coppieters KT, von Herrath MGVan Belle TL, Coppieters KT, von Herrath MG
Diabetes

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

2016-05
Gill RG, Pagni PP, Kufper T, Wasserfall CH, Deng S, Posgai A, Manenkova Y, Bel Hani A, Straub L, Bernstein P, Atkinson…
PLoS One

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

2016-09
Christen S, Coppieters K, Rose K, Holdener M, Bayer MM, Pfeilschifter JM, Hintermann E, von Herrath MG, Aurrand-Lions…
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

2016-09
Sarikonda G, Sachithanantham S, Manenkova Y, Kupfer T, Posgai A, Wasserfall C, Bernstein P, Straub L, Pagni PP,…
Therapeutic Archives

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

2016-09
Suchkov SV, Rose N, Notkins A, Golubnichaia O, von Herrath M, Legg M, Marshall T
Methods in Molecular Biology

Immunosuppressive mechanisms during viral infectious diseases

2016-09
Sarikonda G, von Herrath MG
F1000Res

Recent advances in understanding type 1 diabetes

2016-01
Christoffersson G, Rodriguez-Calvo T, von Herrath M

Principal Investigator

von-herrath

Matthias von Herrath, M.D.

Professor

Dr. von Herrath serves as Director of the Center for Type 1 Diabetes Research in addition to being a full Professor in the Division of Developmental 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.

FlorenceAntequil

Florence Anquetil-Besnard

Postdoctoral Researcher

Biosktech:
I am a French native and I graduated in 2009 from the Faculty of Pharmacy in Angers. I joined the UDEAR in Toulouse where I obtained my PhD in Immunology in 2014 focused on the Pathophysiology of rheumatoid arthritis and the pro-inflammatory effect of anti-citrullinated protein autoantibodies and rheumatoid factor. Finally, I arrived in May 2014 in San Diego and since then worked at La Jolla Insitute as a postdoctoral fellow in Matthias von Herrath Lab.

Research focus:
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. 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 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. I am interested in defining the cytokine milieu in the pancreas from T1D and pre-diabetic donors using immunohistochemistry, molecular biology and bioinformatics tools. My second project aims 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.

Career goals:
I would like to continue a career in scientific research in the field of human autoimmune diseases such as diabetes or rheumatoid arthritis, focused on the role of autoantibodies and cytokines in the diseases.

TeresaRodriguez

Teresa Rodriguez Calvo

Instructor

Biosketch:
I studied Veterinary Medicine at Complutense University (UCM) in Madrid, Spain. In 2012 I completed my PhD in Veterinary Sciences at the Research Center for Animal Health (CISA) in Madrid. In this BSL-3 facility, I acquired my passion for viruses and I focused my research on Immunology and Virology, studying the immune response against Foot and Mouth Disease Virus (FMDV) and Bluetongue Virus (BTV) and specifically the role of dendritic cells during the course of infection. Having been exposed to animal diseases and the use of animal models to better understand human pathology, I moved forward into human research and became interested in the role of viruses on human diseases. In 2012 I joined La Jolla Institute for Allergy and Immunology (LJI), San Diego, United States, as a postdoc under the supervision of Professor Matthias von Herrath and in 2015 I was promoted to Instructor.

Research focus:
In our laboratory we closely collaborate with The Network for Pancreatic Donors with Diabetes (nPOD), which provides valuable tissues from healthy and diabetic donors in order to answer basic questions about the pathogenesis of Type 1 Diabetes (T1D), and ultimately prevent, reverse and cure the disease. Thanks to the nPOD program I studied human tissues like pancreas, spleen and lymph nodes from donors with T1D in order to identify T cells reactive against beta cell antigens, or autoreactive T cells, and how is their distribution and activation status in the pancreas and in other tissues. I have found that CD8 T cells, the main cell type implicated in the destruction of insulin-producing beta cells, infiltrate the exocrine pancreas in high numbers in diabetic donors independently of the presence of insulin and I am very interested in understanding how this could contribute to the pathogenesis of the disease. I am also trying to elucidate whether viral infections make the islets of Langerhans more accessible for these destructive T cells or vice versa.

Career goals:
I am interested in understanding the early changes that take place in the pancreas in individuals at risk of developing the disease. A better understanding of the disease pathogenesis in pre-diabetic and diabetes individuals might help us to early diagnose individuals at risk and to improve therapeutic intervention.

EnriqueMontero

Jose Enrique Montero Casimiro

Visiting Scientist

Biosketch:
Clinical immunologist and Ph.D. in Immunology from the University of Havana. Focused for over 20 years in translational research at startup initiatives in the academy-biopharmaceutical industry interface, leading transitions from discovery to the registration of novel monoclonal antibodies and vaccines for the treatment of autoimmunity and other immune-mediated diseases, at different international scenarios.

Research Focus:
Understanding governing rules triggering and regulating pathological autoimmunity and the neuro-immune networks contribution to this process, particularly in Type 1 Diabetes. It may in-turn cross-fertilize aiming therapeutic inducible autoimmunity for cancer control.

Career Goals:
Committed to continuing contributing to the generation of immunotherapeutic entities for unmet medical needs.

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.

Nathaly Gonzalez

Intern

Natalie von Herrath

Research Technician II

Yasaman Lejavardi

Research Technician I

SomayehSabouri

Somayeh Sabouri

Postdoctoral Fellow

Bio sketch:
I finished my MSc in Molecular Cell Biology, Tabriz, Iran in 2009. Immediately after, I moved to Japan to pursue my Ph.D. in the field of Immunogenetics, laboratory of Prof. Tasuku Honjo, Department of Immunology and Genomic Medicine at Kyoto University. After my Ph.D. graduation, in 2014 I joined Dr. von Herrath laboratory as a postdoctoral fellow.

Research project:
The aim of my project is to find out the role of the human herpesviruses-6 (HHV-6) in the pathogenies of Type 1 diabetes (T1D). 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. I am interested in looking at the various HHV-6 proteins in the human pancreas obtained from the Network for Pancreatic Organ Donors with Diabetes (nPOD) by Immunohistochemistry assays. This study will help us to determine a possible role of herpesviruses in the Immunopathogenesis of T1D which can lead to preventative measures for future clinical trials.

Career Goals:
Continuing my scientific research mainly focused on the human disease, particularly on type 1 diabetes.

SowieSachithanantham

Sowbarnika Sachithanantham

Research Technician IV/Lab Manager

Education:
2006 – B.S. in Biotechnology Bharathaiar University, Tamil nadu, India
2009 – M.S. in Cellular and Molecular Biology, San Diego State University, CA, USA
I started working in the laboratory of Dr. Matthias von Herrath in 2009 as a Research Tech I. Currently, I am a Research Tech IV / Lab Manager.

Research Focus / Responsibilities:
My main research focus is to examine the potential of using therapeutics in various Type 1 Diabetes mouse models, including the NOD/ShiLtJ, RIP GP and NP mice.
In association with Dr. Christoffersson, I am also examining the role of bystander cells within the pancreas of T1D susceptible mouse strains. In addition, our lab is a contract research organization for Novo Nordisk and my responsibilities are to plan, manage, and ensure the completion of the various contract research projects.

Career Goals:
I intend to have a career in translational research.

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.