Kevan Herold, MD
Research & Publications
The work in our laboratory involves translational studies in human immunology, focused on Type 1 diabetes. We are carrying out clinical studies of new immune therapies, in particular humanized anti-CD3 monoclonal antibody, and study the metabolic and immunologic effects of these interventions on the disease process. We showed how treatment with this drug, teplizumab, can delay or prevent the onset of diabetes in relatives who are at risk for disease. We are studying the ability of this intervention to prevent diabetes alone or with other treatments. We have identified a novel regulatory mechanism that we believe is involved in the progression to autoimmune diabetes and plan to expand these studies so that precise therapies can be curtailed to patients.
In addition, we are interested in developing new ways to improve beta cell function and mass which are compromised in all forms of diabetes. We are testing whether immune interventions can lead to spontaneous restoration of beta cell mass and developing new approaches to stimulate beta cell regeneration. Our studies to address this goal involve studies in patients and in animal models of the disease.
We also have an interest in autoimmune diseases that are occur in patients with cancers who are treated with new immune therapies such as checkpoint inhibitors that are given to patients with cancers. We are studying the mechanisms that lead to these adverse events with the objective to prevent them from occurring.
Specialized Terms: Type 1 diabetes; Immune therapy; Autoimmunity
Extensive Research Description
The pathogenesis and treatment of autoimmune disease, in particular Type 1 diabetes.
Studies involve clinical trials with patients and investigations of the mechanism of action of immune therapies and the pathogenesis of disease in patients as well as in animal models when needed to address what cannot be studies in humans. Over the past 7 years, our lab has carried out trials of a humanized non-FcR binding anti-CD3 monoclonal antibody in patients and has studied the mechanism of drug action. These clinical studies have suggested novel mechanisms of immune regulation that are now to be addressed with new clinical studies.
Diabetes Mellitus, Type 1; Endocrine System Diseases; Immune System Diseases; Metabolism; Autoimmunity; Polyendocrinopathies, Autoimmune; Translational Research, Biomedical
Public Health Interests
- Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patientsPierce CA, Preston-Hurlburt P, Dai Y, Aschner CB, Cheshenko N, Galen B, Garforth SJ, Herrera NG, Jangra RK, Morano NC, Orner E, Sy S, Chandran K, Dziura J, Almo SC, Ring A, Keller MJ, Herold KC, Herold BC. Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients Science Translational Medicine 2020, 12: eabd5487. PMID: 32958614, PMCID: PMC7658796, DOI: 10.1126/scitranslmed.abd5487.
- An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 DiabetesHerold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes New England Journal Of Medicine 2019, 381: 603-613. PMID: 31180194, PMCID: PMC6776880, DOI: 10.1056/nejmoa1902226.
- Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint InhibitorsStamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H, Weiss SA, Gettinger S, Sznol M, Young A, Rushakoff R, Lee J, Bluestone JA, Anderson M, Herold KC. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors Diabetes 2018, 67: dbi180002. PMID: 29937434, PMCID: PMC6054443, DOI: 10.2337/dbi18-0002.
- β Cell death and dysfunction during type 1 diabetes development in at-risk individualsHerold KC, Usmani-Brown S, Ghazi T, Lebastchi J, Beam CA, Bellin MD, Ledizet M, Sosenko JM, Krischer JP, Palmer JP. β Cell death and dysfunction during type 1 diabetes development in at-risk individuals Journal Of Clinical Investigation 2015, 125: 1163-1173. PMID: 25642774, PMCID: PMC4362259, DOI: 10.1172/jci78142.
- Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and PatientsWaldron-Lynch F, Henegariu O, Deng S, Preston-Hurlburt P, Tooley J, Flavell R, Herold KC. Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients Science Translational Medicine 2012, 4: 118ra12. PMID: 22277969, PMCID: PMC4131554, DOI: 10.1126/scitranslmed.3003401.
|Diabetes Mellitus - Type 1||TrialNet TOPPLE Study for People with Type 1 Diabetes|
|Diabetes Mellitus - Type 1||Hydroxychloroquine in Individuals At-risk for Type 1 Diabetes Mellitus (TN-22)|
|Children's Health; Diseases of the Endocrine System; Genetics - Adult; Genetics - Pediatric; Mental Health & Behavioral Research||Yale Center for Clinical Investigation (YCCI) Specimen and Data Repository|
|Diseases of the Nervous System||Imaging pancreatic beta-cells with PET neuroimaging agent 11C-PHNO|
|Diabetes Mellitus - Type 1; Diseases of the Endocrine System; Diseases of the Nervous System||Impact of Hypoglycemia on Brain Ketone and Neurotransmitter Metabolism in Type 1 DM|
|Children's Health; Diabetes Mellitus - Type 1; Diseases of the Endocrine System||Pathway to Prevention Study|
|Children's Health; Diabetes Mellitus - Type 1||Type 1 Diabetes Extension Study (T1DES)|