Arlene H. Sharpe

Research Statement

AI generated · 10h ago

Arlene H. Sharpe's research centers on the inhibitory pathways that restrain T cell responses, particularly the PD-1/PD-L1 axis in tolerance and autoimmunity, the subject of a 2008 review that remains her most-cited indexed work. Her earlier demonstration that loss of CTLA-4 causes massive lymphoproliferation and fatal multiorgan destruction established the molecule as a critical negative regulator, while later studies on PD-L1's role in the development and function of induced regulatory T cells and on tissue PD-L1 mediating peripheral T cell tolerance extended this logic into peripheral immune regulation. Beyond these lead-author reviews, Sharpe contributed as a middle author to restoring function in exhausted CD8 T cells during chronic viral infection, a study that helped connect checkpoint biology to therapeutic reversal of T cell exhaustion, and to the identification of PD-L2 as a second ligand for PD-1 that inhibits T cell activation. Her work has unfolded alongside collaborators including Ana Carrizosa Anderson and Alexander Yu Rudensky. Across these outputs, the through-line is a sustained inquiry into how costimulatory and coinhibitory signals shape tolerance, autoimmunity, and antitumor immunity.

Most Cited Works

Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4

E A Tivol, F Borriello, A N Schweitzer, W P Lynch, J A Bluestone, A H Sharpe

Immunity1995

2,913Citations

Defining ‘T cell exhaustion’

Christian U Blank, W Nicholas Haining, Werner Held, Patrick G Hogan, Axel Kallies, Enrico Lugli, Rachel C Lynn, Mary Philip, Anjana Rao, Nicholas P Restifo,

Research Areas

T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesPsoriasis: Treatment and PathogenesisGlioma Diagnosis and Treatment

Affiliations & Education

Employment

2023–present· now
Harvard University(US)
Kolokotrones University Professor
2023–present· now
Gene Lay Institute of Immunology & Inflammation, Brigham & Women's Hospital, Massachusetts General Hospital, Harvard Medical School(US)
Vice- Director
2018–present· now
Harvard Medical School(US)
Chair · Immunology
2004–2022
Harvard Medical School

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