S. Alice Long, PhD
Dr. Alice Long received her BS degree in Biology from Macalester College in St. Paul, MN, and earned her PhD in Immunology from Emory University in Atlanta, GA. She then pursued post-doctoral studies at the University of California at Davis studying the etiology and pathogenesis of primary biliary cirrhosis, an autoimmune disease of the liver. She next joined a Seattle-based biotechnology company, Xcyte Therapies, where she helped develop adoptive T-cell therapies for multiple diseases. In 2005, she joined Benaroya Research Institute (BRI) as a staff scientist in the laboratory of Dr. Buckner where she applied her T-cell therapy experience to adoptive Treg therapy in T1D while studying the etiology and pathogenesis of T1D. In 2011, she joined the faculty at BRI and is currently a Research Associate Member and Manager of the Human Immunophenotyping Core.
Area of Research
Dr. Long’s lab is a translational immunology lab focused on discovering how the adaptive immune system is dysregulated in human autoimmunity. Specifically, her current research includes three inter-related projects in the setting of T1D.
- Causes and consequences of reduced response to IL-2 in T1D subjects,
- Cellular definition, function and stability of CD8 T cell exhaustion associated with beneficial disease outcomes and
- Identification of biomarkers of T1D progressors vs non-progressors.
Translational Research Program
Herold 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. N Engl J Med. 2019 Jun 9;. doi: 10.1056/NEJMoa1902226. [Epub ahead of print] PMID: 31180194
Haller MJ, Long SA, Blanchfield JL, Schatz DA, Skyler JS, Krischer JP, Bundy BN, Geyer SM, Warnock MV, Miller JL, Atkinson MA, Becker DJ, Baidal DA, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Herold KC, Marks JB, Moran A, Rodriguez H, Russell WE, Wilson DM, Greenbaum CJ. Low-Dose Anti-Thymocyte Globulin Preserves C-Peptide, Reduces HbA1c, and Increases Regulatory to Conventional T-Cell Ratios in New-Onset Type 1 Diabetes: Two-Year Clinical Trial Data. Diabetes. 2019 Jun;68(6):1267-1276. doi: 10.2337/db19-0057. Epub 2019 Apr 9. PMID: 30967424.
Habib T, Long SA, Samuels PL, Brahmandam A, Tatum M, Funk A, Hocking AM, Cerosaletti K, Mason MT, Whalen E, Rawlings DJ, Greenbaum C, Buckner JH. Dynamic Immune Phenotypes of B and T Helper Cells Mark Distinct Stages of T1D Progression. Diabetes. 2019 Jun;68(6):1240-1250. doi: 10.2337/db18-1081. Epub 2019 Mar 20. PubMed PMID: 30894366
Long SA, Thorpe J, Herold KC, Ehlers M, Sanda S, Lim N, Linsley PS, Nepom GT, Harris KM. Remodeling T cell compartments during anti-CD3 immunotherapy of type 1 diabetes. Cell Immunol. 2017 Sep;319:3-9. doi: 10.1016/j.cellimm.2017.07.007. Epub 2017 Aug 18. PMID: 28844471, PMCID: PMC5614459
Schwedhelm K, Thorpe J, Murray SA, Gavin M, Speake C, Greenbaum C, Cerosaletti K, Buckner J, Long SA. Attenuated IL-2R signaling in CD4 memory T cells of T1D subjects is intrinsic and dependent on activation state. Clin Immunol. 2017 Jun 20;181:67-74. doi: 10.1016/j.clim.2017.06.004. PMID: 28645874
Long SA, Thorpe J, DeBerg H, Gersuk V, Eddy J, Harris K, Ehlers M, Herold K, Nepom G and Linsley P. Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes. Sci.Immunol.1,eaai 7793 2016 18November 2016. PMID: 28664195
Rigby MR, Harris KM, Pinckney A, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, Griffin KJ, Tsalikian E, Gottlieb PA, Greenbaum CJ, Sherry NA, Moore WV, Monzavi R, Willi SM, Raskin P, Keyes-Elstein L, Long SA, Kanaparthi S, Lim N, Phippard D, Soppe CL, Fitzgibbon ML, McNamara J, Nepom GT, Ehlers MR and the Immune Tolerance Network (ITN). Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients. J Clin Invest. 2015 Aug 3;125(8):3285-96. PMID: 26193635, PMCID: PMC4623571.
Cerosaletti K, Schneider A, Schwedhelm K, Frank I, Tatum M, Wei S, Whalen E, Greenbaum C, Kita M, Buckner J, Long SA. Multiple autoimmune-associated variants confer decreased IL-2R signaling in CD4+CD25hi T cells of type 1 diabetic and multiple sclerosis patients. PLoS One 2013; 8(12):e83811. PMCID: PMC3871703.
Long SA, Rieck M, Sanda S, Bollyky JB, Samuels PL, Goland R, Ahmann A, Rabinovitch A, Aggarwal S, Phippard D, Turka LA, Ehlers MR, Bianchine PJ, Boyle KD, Adah SA, Bluestone JA, Buckner JH, Greenbaum CJ; Diabetes TrialNet, Immune Tolerance Network. Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs β-cell function. Diabetes 2012; 61(9):2340-2348.
Long SA, Cerosaletti K, Ho J, Jia-Yin W, Tatum M, Wei S, Shilling H, Buckner J. An autoimmune-associated variant in PTPN2 reveals an impairment of IL-2R signaling in CD4+ T cells. Genes Immun 2011; 12(2):116-125.
Long SA, Cerosaletti K, Bollyky PL, Tatum M, Shilling H, Zhang S, Zhang Z-Y, Pihoker C, Sanda S, Greenbaum C, Buckner JH. Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4+CD25+ regulatory T cells of T1D subjects. Diabetes 2010; 59(2):407-415.