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Linda Sherman, Ph.D.

Professor
Department of Immunology and Microbial Science
California Campus
Laboratory Website
lsherman@scripps.edu
(858) 784-8052

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

Recognition of Self and Tumor Antigens

Fundamental to the strategy of the immune system is discrimination between self and non-self. This enables the immune system to respond to and eliminate foreign pathogens without harming one's own tissues. Autoimmune disease represents aberrant immune destruction of self-tissue, whereas other diseases such as cancer are, in part, due to immune tolerance of self. One goal of our laboratory is to augment the ability of T lymphocytes to respond to certain self-antigens in order to eliminate tumor cells. To this end, we utilize a variety of transgenic murine models in order to study autoimmunity and tumor immunity. In particular, we are studying how expression of proteins in normal tissues alters immune recognition and responsiveness to antigens of these proteins when they are subsequently encountered on normal tissue or tumor cells. We use similar models to probe defects in immune tolerance that result in autoimmune destruction of pancreatic islets leading to type 1 diabetes.

Education

Ph.D., Biology, Massachusetts Institute of Technology, 1976

Selected References

Wei, C.H., and Sherman, L.A. 2007. N-Terminal trimer extension of nominal CD8T cell epitopes is sufficient to promote cross-presentation to cognate CD8 T cells in vivo. J. Immunol. 179(12):8280-8286

Wong, S.B.J., Bos, R., Sherman, L.A. 2008. Tumor specific CD4+ T cells render the tumor environment permissive for infiltration by low avidity CD8+ T cells. J. Immunol. 180:3122–3131

Redmond, W.L., Wei, C.H., Kreuwel, H.T.C., Sherman, L.A. 2008. The apoptotic pathway contributing to the deletion of naïve CD8 T cells during induction of peripheral tolerance to a cross-presented self-antigen. J. Immunol.180(8):5275-82.

Verdeil, G., Marquardt, K., Surh, C.D., Sherman, L.A.2008. Adjuvants targeting innate and adaptive immunity synergize to enhance tumor immunotherapy. PNAS. 105(43):16683-8 PMCID: PMC2575480

Hamilton-Williams, E.E., Martinez, X., Clark, J., Howlett, S., Hunter, K.M., Rainbow, D.B., Wen, L., Shlomchik, M.J., Katz, J.D., Beilhack, G.F. Wicker, L.S., Sherman, L.A. 2009. Expression of diabetes-associated genes by dendritic cells and CD4 T-cells drives the loss of tolerance in nonobese diabetic mice.  J. Immunol. 183:1533-1541. PMCID: PMC2733871

Hamilton-Williams EE, Wong SB, Martinez X, Rainbow DB, Hunter KM, Wicker LS, Sherman LA. 2010. Idd9.2 and Idd9.3 protective alleles function in CD4+T-cells and non-lymphoid cells to prevent expansion of pathogenic islet specific CD8+T-cells. Diabetes. Jun; 59(6):1478-86. PMID:20299469; PMCID:PMC2874709

Bos, R., Sherman, LA. 2010. CD4+ T-cell help in the tumor milieu is required for recruitment and cytolytic function of CD8+ T lymphocytes. Cancer Res. Nov;70(21):8368-77. PMID: 20940398; PMCID:PMC2970736

Hamilton-Williams EE, Cheung J, Rainbow DB, Hunter KM, Wicker LS, Sherman LA. 2012.  Cellular mechanisms of restored β-cell tolerance mediated by protective alleles of Idd3 and Idd5. Diabetes. 2012 Jan;61(1):166-74. Epub 2011 Nov 21. PMID:22106155; PMCID:PMC:3237671

Vosganian GS, Bos R, Sherman LA.  2012. Immunologic effects of an orally available BRAFV600E inhibitor in BRAF wild-type murine models.  J Immunother. July;35(6):473-7. PMID: 22735805; PMCID:PMC:3485086

Maine CJ, Hamilton-Williams EE, Cheung J, Stanford SM, Bottini N, Wicker LS, Sherman LA. 2012. PTPN22 alters the development of regulatory T cells in the thymus. J Immunol. Jun;188(11):5267-75. PMID: 22539785; PMCID: PMC: 3358490 

Rinke B, Marquardt K, Cheung J, Sherman LA. 2012. Functional differences between low-and high-affinity CD8+ T cells in the tumor environment. Oncolmmunology 1;1(8)1239-1247. PMID: 10547847; PMCID: PMC: 3518496 

Lin X., Hamilton-Williams E.E., Rainbow D.B., Hunter K.M., Dai Y.D., Cheung J., Peterson L.B., Wicker L.S., Sherman L.A. 2013. Genetic interactions among Idd3, Idd5.1, Idd5.2 and Idd5.3 protective loci in the NOD mouse model of type 1 diabetes. J Immunol. April:190(7):3109-20.  PMID: 23427248; PMCID: PMC36088

Hamilton-Williams, E.E., Rainbow, D.B., Cheung, J., Christensen, M., Lyons, P.A., Peterson, L.B., Steward, C.A., Sherman, L.A., Wicker, L.S. 2013. Fine mapping of type 1 diabetes regions Idd9.1 and Idd9.2 reveals genetic complexity. Mamm Genome. Oct;24(9-10):358-75. PMID: 23934554 [PubMed - in process] PMCID: PMC3824839

Wu D., Zhou W., Enouz S., Orru V.,Stanford S.M., Maine C.J., Rapini N., Sawatzke K., Engel I., Fiorillo E., Sherman L.A., Kronenberg M., Zehn D., Peterson E., Bottini N Autoimmunity-associated LYP-W620 does not impair thymic negative selection of autoreactive T cells PLOS One 2014: Feb 3;9(2)PMID:24498279 PMCID:PMC3911918

Maine C.J., Marquardt K., Cheung J., Sherman L.A. PTPN22 controls the germinal center by influencing the numbers and activity of T follicular helper cells 2014 PMID: 24453256 [PubMed - indexed for MEDLINE] PMCID: PMC3933017 [Available on 2015/2/15].

SmithT.R.F., Verdeil G, Marquardt K, and Sherman LA. 2014. Contribution of TCR signaling strength to CD8+ T Cell Peripheral Tolerance Mechanisms. J Immunol. Oct 1;193(7):3409-16. doi: 10.4049/jimmunol.1401194. Epub 2014 Aug 25.PMID: 25156361

Maine, C.J., Kristi Marquardt, John C. Scatizzi, K. Michael Pollard, Dwight H. Kono, Linda A. Sherman. 2014, The Effect of the Autoimmunity-Associated Gene, PTPN22, on the BXS Model of Lupus, Clinical Immunology, in press.