CV Science

Guillaume DOROTHEE PhD - Group Leader - Neuroimmunology

Course and current status

Since 2012:  Tenured Senior Investigator (CR1), Immune System, Neuroinflammation & Neurodegenerative Diseases laboratory - INSERM UMRS 938 - Hôpital Saint-Antoine, Paris, France.

2007-2012:  Junior Investigator INSERM 3/5 years, Immune System & Conformational Diseases laboratory - INSERM UMRS 938 - Hôpital Saint-Antoine, Paris, France.

2006-2007:  Post-doctoral Fellow, Immunity and Cancer laboratory - INSERM U653 - Institut Curie, Paris, France.

2004-2006  Research Fellow, Laboratory of Antimicrobial Immunity, Memorial Sloan-Kettering Cancer Center, New York, USA.

2003-2004  Post-doctoral Fellow, Cytokines and Human Tumor Immunology laboratory - INSERM U487 - Institut Gustave Roussy, Villejuif, France.

1999-2003  Ph.D. student, INSERM U487 laboratory, Institut Gustave Roussy, Villejuif, France

Scientific summary

Adaptive cellular immunity in Alzheimer's disease

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive loss of memory and cognitive functions. AD neuropathology is defined by extracellular deposits of Aβ amyloid peptide, and neurofibrillary tangles corresponding to intraneuronal fibrillar deposits of hyper- and abnormally phosphorylated Tau proteins. Compelling evidences support the involvement of immune responses in the pathophysiology of AD. Chronic neuroinflammation mediated by microglia and astrocytes is associated with disease progression and has been implicated in the neuropathological process. Besides such innate immune neuroinflammation, more recent data emphasize a role of adaptive immunity in the pathophysiology of the disease. Importantly, GWAS studies show an association between susceptibility to AD and immune genes implicated in T cell responses. However, the nature of T cell populations implicated and their impact on disease progression remain poorly defined. Based on transgenic mouse models of both amyloid and Tau pathologies, our objective is to decipher the role of T cell responses in the pathophysiology of AD, and define innovative immunotherapy approaches.

Biomarkers in early Alzheimer's disease

Identification of biomarkers allowing detection of AD patients in the predementia stage (prodromal AD) or even presymptomatic phase is a major objective for the development and clinical evaluation of disease-modifying drugs in AD. Innate and adaptive immune responses constitute a promising source of such potential biomarkers. We are interested in evaluating the diagnostic and prognostic value, in early human AD, of a panel of immune-related blood biomarkers.

Other Research Interests

- Regulation of CD4+ T cell responses

- Antimicrobial immunity
- T cell responses to intracellular bacteria
- Innate recognition mechanisms

- Antitumor immunity
- T cell-mediated cytotoxicity
- Cancer immunotherapy