We have had a longstanding interest in understanding the precise self-recognition events involved in initiation and progression of autoimmune diseases and in developing novel therapeutic strategies that prevent disease progression. In these pursuits we have developed and characterized autoimmune animal models for several human diseases including multiple sclerosis, heart failure, sudden hearing loss, infertility, prostatitis, interstitial cystitis/pelvic pain syndrome, and breast failure. However, more recently, we have focused our attention on harnessing and focusing the full strength of the autoimmune response to provide safe and effective immunity against the development of diseases we confront with age. As such we have pioneered the concept of ‘immunoprevention’ of breast cancer by providing proof-of-principle that safe and effective protection against the development of breast cancer may be induced by vaccination against ‘retired’ self-proteins that are no longer expressed with age at immunogenic levels in any normal tissues but are overexpressed in newly invigorated emerging breast tumors. Thus, ‘retired’ proteins may substitute for unavailable pathogens as targets for developing prophylactic immunity against tumors we confront with age like breast, ovarian, and prostate cancer. Our laboratory is currently involved in bringing our ‘immunoprevention’ strategy from bench-to-bedside in clinical trials designed to prevent the more aggressive and lethal forms of breast cancer.
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Collaborators:
Altuntas CZ, Daneshgari F, Veizi E, Izgi K, Bicer F, Ozer A, Grimberg KO, Bakhautdin B, Sakalar C, Tasdemir C, Tuohy VK. A novel murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) induced by immunization with a spermine binding protein (p25) peptide. American Journal of Physiology - Regulation, Integrative, and Comparative Physiology 2013;304:R415-422
Altuntas CZ, Daneshgari F, Izgi K, Bicer F, Ozer A, Sakalar C, Grimberg KO, Sayin I, Tuohy VK. Connective tissue and its growth factor CTGF distinguish the morphometric and molecular remodeling of the bladder in a model of neurogenic bladder. American Journal of Physiology - Renal Physiology 2012;303:F1363-1369
Kesaraju P, Jaini R, Johnson JM, Altuntas CZ, Gruden JJ, Sakalar C, Tuohy VK. Experimental autoimmune breast failure: a model for lactation insufficiency, postnatal nutritional deprivation, and prophylactic breast cancer vaccination. American Journal of Pathology 2012;181:775-784
Altuntas CZ, Daneshgari F, Sakalar C, Goksoy E, Gulen MF, Kavran M, Qin J, Li X, Tuohy VK. Autoimmunity to uroplakin II causes cystitis in mice: a novel model of interstitial cystitis. European Urology 2012;61:193-200
Altuntas CZ, Jaini R, Kesaraju P, Jane-wit D, Johnson JM, Covey K, Flask CA, Dutertre M, Picard JY, Tuohy VK. Autoimmune mediated regulation of ovarian tumor growth. Gynecologic Oncology 2012;124:98-104
Tuohy VK, Jaini R. Prophylactic cancer vaccination by targeting functional non-self. Annals of Medicine 2011;43:356-365
Tuohy VK. A prophylactic vaccine for breast cancer? Why not? Breast Cancer Research 2010;12:405
Jaini R, Kesaraju P, Johnson JM, Altuntas CZ, Jane-Wit D, Tuohy VK. An autoimmune-mediated strategy for prophylactic breast cancer vaccination. Nature Medicine. 2010;16:799-803. http://www.nature.com/nm/journal/v16/n7/abs/nm.2161.html
Kang Z, Altuntas CZ, Gulen MF, Liu C, Giltiay N, Qin H, Liu L, Qian W, Ransohoff RM, Bergmann C, Stohlman S, Tuohy VK, Li X. Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis. Immunity 2010;32:414-25
Gulen MF, Kang Z, Bulek K, Youzhong W, Kim TW, Chen Y, Altuntas CZ, Sass Bak-Jensen K, McGeachy MJ, Do JS, Xiao H, Delgoffe GM, Min B, Powell JD, Tuohy VK, Cua DJ, Li X. The receptor SIGIRR suppresses Th17 cell proliferation via inhibition of the interleukin-1 receptor pathway and mTOR kinase activation. Immunity 2010;32:54-66
Staschke KA, Dong S, Saha J, Zhao J, Brooks NA, Hepburn DL, Xia J, Gulen MF, Kang Z, Altuntas CZ, Tuohy VK, Gilmour R, Li X, Na S. IRAK4 kinase activity is required for Th17 differentiation and Th17-mediated disease. Journal of Immunology 2009;183:568-577
Tigno-Aranjuez JT, Jaini R, Tuohy VK, Lehmann PV, Tary-Lehmann M. Encephalitogenicity of complete Freund's adjuvant relative to CpG is linked to induction of Th17 cells. Journal of Immunology 2009;183:5654-5661
Buniel MC, Geelan-Hansen K, Weber PC, Tuohy VK. Immunosuppressive therapy for autoimmune inner ear disease. Immunotherapy 2009;1:425-434