Denise Faustman, M.D.,Ph.D.
Type I diabetes-Autoimmunity and Islet Regeneration
Dr. Faustman’s current research program investigates human and murine Type I diabetes. She specifically investigates immunologic and genetic derangements as they relate to phenotypes of disease expression. In 1991, her laboratory discovered MHC class I with contained endogenous peptides was a pathway for self-tolerance and this pathway was interrupted in diverse human and murine autoimmune diseases. In a well-established autoimmune model, the NOD mouse, the defect tracked to a proteasome defects in intracellular processing. This underlying defect additionally ablated activation of a central transcription factor, NF-kB and confers autoimmune specific phenotypes of accelerated apoptosis in response to TNF. New therapies are being developed based on these underlying defects including interventions that can effectively halt existing disease. In the case of type 1 diabetes, her work has shown that some animal models have the ability to regenerate the existing islet cells in the pancreas and thus confer an effective permanent disease reversal without the introduction of stem cells. The promise of this work allows her to move these projects forward into the clinic in a large translational project at the Massachusetts General Hospital. Two major projects are currently ongoing:
1. Okubo Y, Mera T, Wang L, Faustman DL. Homogeneous expansion of human T-regulatory cells via tumor necrosis factor receptor 2. Sci Rep. 2013;3:3153. doi: 10.1038/srep03153. PMID: 24193319 [PubMed - in process]
2. Faustman DL, Wang L, Okubo Y, Burger D, Ban L, Man G, Zheng H, Schoenfeld D, Pompei R, Avruch J, Nathan DM. Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes.vPLoS One. 2012;7(8):e41756. doi: 10.1371/journal.pone.0041756.PMID: 22905105 [PubMed - indexed for MEDLINE]
3. Limei Wang, Nicholas Fraser Lovejoy, Denise L. Faustman. Persistence of prolonged C-peptide production in type 1 diabetes as measured with an ultrasensitive C-peptide assay. Diabetes Care. 2012 March; 35(3): 465–470. PMCID: PMC3322715.
4. Francisco Dieguez-Acuña, Shohta Kodama, Yoshiaki Okubo, Ana Cristina Paz, Steven P Gygi, Denise L Faustman. Proteomics identifies multipotent and low oncogenic risk stem cells of the spleen. Int J Biochem Cell Biol. 2010; 42(10): 1651–1660. PMCID: PMC2891339.
5. Ban L, Zhang J, Wang L, Kuhtreiber W, Burger D, Faustman DL. Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism. Proc Natl Acad Sci U S A. 2008;105(36):13644-9. PMCID: PMC2533243
6. Dieguez-Acuna FJ, Gygi SP, Davis M, Faustman DL. Splenectomy: a new treatment option for ALL tumors expressing Hox-11 and a means to test the stem cell hypothesis of cancer in humans. Leukemia. 2007 Oct;21(10):2192-4.
7. Faustman DL. Permanent reversal of diabetes in NOD mice. Science. 2007 Jul 13;317(5835):196.
8. Tran SD, Kodama S, Lodde BM, Szalayova I, Key S, Khalili S, Faustman DL, Mezey E. Reversal of Sjogren's-like syndrome in non-obese diabetic mice. Ann Rheum Dis. 2007 Jun;66(6):812-4.
9. Faustman DL, Tran SD, Kodama S, Lodde BM, Szalayova I, Key S, Toth ZE, Mezey E. Comment on papers by Chong et al., Nishio et al., and Suri et al. on diabetes reversal in NOD mice. Science. 2006 Nov 24;314(5803):1243; author reply 1243.
10. Yan G, Shi L, Penfornis A, Faustman DL. Impaired processing and presentation by MHC class II proteins in human diabetic cells. J Immunol. 2003;170:620-7.
11. Ryu S, Kodama S, Ryu K, Schoenfeld DA, Faustman DL. Reversal of established autoimmune diabetes by restoration of endogenous ß-cell function. J Clin Invest. 2001; 108:63-72.