UCLA Neuroscience Program Ph.D. Admissions Neuroscience Faculty UCLA and Beyond  



Daniel Kaufman
Autoimmune Disease, Transdifferentiation, in vivo Imaging, Neurorepair and Parkinson's Disease

Work Email Address:  dkaufman@mednet.ucla.edu
Home Page: http://www.uclaaccess.ucla.edu/cfm/access_faculty.cfm?FacultyKey=1366

Work Address:
CHS
CHS
Phone Numbers:
206-3350 Laboratory
310-794-9664 Office

Selected Publications:

Escande-Beillard, N., Washburn, L., Zekzer, D., Wu, Z-P., , Eitan, S., Ivkovic, S., Lu, Y., Dang, H., Middleton, B., Yoshimura, Y., Evans, C.J., Joyce, S., Tian, J., and Kaufman, D.L. Neurons preferentially respond to self-major histocompatibility complex class I allele products regardless of peptide presented. J. Immunol. 2010; in press: .
Tian J, Kaufman DL Antigen-based therapy for the treatment of type 1 diabetes. Diabetes. 2009; 58: 1939-1946.
Tian, J., Dang, H., von Boehmer, H., Jaeckel, E., Kaufman, D.L Transgenically-induced GAD tolerance curtails the development of early ß-cell autoreactivities but causes the subsequent development of supernormal autoreactivities to other ß-cell antigens. Diabetes 2009; Dec.: .
L.R. Washburn, H. Dang, J. Tian, D.L. Kaufman. The postnatal maternal environment influences diabetes development in nonobese diabetic mice. J. Autoimmunity 2007; 28: 19-23.
Tian, J., Zekzer, D., Lu, Y., Dang, H.and Kaufman, DL. B cells are crucial for determinant spreading of T cell autoimmunity among b-cell antigens in diabetes-prone NOD mice.. Journal of Immunology 2006; 176: 2654-2661.
Lu, Y., Dang, H., Middleton, B., Zhang, Z., Washburn, L., Stout, D.B., Campbell-Thompson, M., Atkinson, M.A., Phelps, M., Gambhir, S.S, Tian, J., and Kaufman, D.L. Noninvasive imaging of islet grafts using positron emission tomography.. PNAS 2006; 103: 11294-11299.
Olcott, A.P., Tian, J., Walker, V., Dang, H., Middleton, B., Adorini, L. Washburn, and Kaufman, D.L Antigen-based therapies utilizing ignored determinants of beta-cell antigens can more effectively inhibit late-stage autoimmune disease in diabetes-prone mice.. J. Immunol. 2005; 175: 1991-1999.
Tian, J., Olcott A.P. and Kaufman, D.L. Antigen-based immunotherapy drives the precocious developement of autoimmunity.. J. Immunol. 2002; 169: 6564-6569.
Kaufman, D.L and Tobin, A.J. Glutamic Acid Decarboxylases: Insights into Neural Signaling and Autoimmune Diabetes.. Encyclopedia of Molecular Medicine 2002; 1459-1462.
Kaufman, D.L and Tobin, A.J. Glutamic Acid Decarboxylases: Insights into Neural Signaling and Autoimmune Diabetes.. Encyclopedia of Molecular Medicine 2001; .
Jide Tian and Daniel Kaufman. Lipopolysacharide-activated B cells as immunotherapy in NOD mice .. J. Immunology , 2001; 167: 1081-1089.
Jide Tian, Silvia Gregori, Luciano Aldorini and Daniel L. Kaufman. The frequency of high avidity T cells determines the chronology of determinant spreading.. J. Immunology 2001; 166: 7144-7150.
Jide Tian and Daniel L. Kaufman Control of Autoimmune Diabetes. (commentary).. Science 2000; 287: 191a.
Tian et al. Antigen-based Immunotherapy: From Animal Models to Man?. Immunology Today 1999; 20: 190-195.
Tian, J, et al. GABA-A receptors mediate inhbition of T cell responses.. J. Neuroimmunology 1999; 96: 21-28.
Tian J. et al. Selective priming of Th2 cells and induction of active tolerance in pre-diabetic mice by administration of soluble insulin.. Diabetologia. 1998; 41: 237-240.
Olcott, A.P., Tian, J. and Kaufman, D.L. Autoantigen-based immunotherapy for human IDDM.. Diabetes Prevention and Therapy 1996; 10: 20-21.
Kaufman DL GAD autoantibodies.. In: Autoantibody Textbook. 1996; 308-313.
Kaufman DL and Tobin AJ. Glutamate decarboxylase, GABA and autoimmunity.. In: GABA receptors, transporters and metabolism. 1996; 23-30.
Tian, J., et al. Nasal administration of glutamate decaboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes.. J. Exp. Med. 1996; 183: 1561-1567.
Atkinson MA et al. Cellular immunity to an epitope common to glutamate decarboxylase and Coxsackie virus in insulin-dependent diabetes.. J. Clin. Invest.. 1994; 94: 2125-2129.
Tian et al. T cell cross-reactivity between coxsackievirus and glutamate decarboxylase is assocaited with a murine diabetes susceptability allele.. J. Exp. Med.. 1994; 180: 1979-1984.
Kaufman DL and Tobin AJ. Glutamate decaroxylases in insulin-dependent diabetes.. Trends in Pharmacological Sciences. 1993; 14: 107-109.
Atkinson et al. Islet cell autoantibody reactivity to glutamate decarboxylase in insulin-dependent diabetes.. J. Clinical. Invest. 1993; 91, : 350-355.
Kaufman, D.L., et al. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes.. Nature 1993; 366: 69-72.
Atkinson, M.A.et al. Peripheral blood mononuclear cells respond to glutamate decarboxylase in insulin-dependent diabetes.. Lancet 1992; 339: 458-459.
Lu, Y Dang, H Middleton, B Campbell-Thompson, M Atkinson, MA Gambhir, SS Tian, J Kaufman, DL Long-term monitoring of transplanted islets using positron emission tomography.. Molecular therapy : the journal of the American Society of Gene Therapy. 2006; 14(6): 851-6.
Tian, J Lu, Y Zhang, H Chau, CH Dang, HN Kaufman, DL Gamma-aminobutyric acid inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model.. Journal of immunology (Baltimore, Md. : 1950) . 2004; 173(8): 5298-304.
Olcott, AP Tocco, G Tian, J Zekzer, D Fukuto, J Ignarro, L Kaufman, DL A salen-manganese catalytic free radical scavenger inhibits type 1 diabetes and islet allograft rejection.. Diabetes. . 2004; 53(10): 2574-80.
Lu, Y Dang, H Middleton, B Zhang, Z Washburn, L Campbell-Thompson, M Atkinson, MA Gambhir, SS Tian, J Kaufman, DL Bioluminescent monitoring of islet graft survival after transplantation.. Molecular therapy : the journal of the American Society of Gene Therapy. . 2004; 9(3): 428-35.
Tian, J Lu, Y Hanssen, L Dang, H Kaufman, DL Memory and effector T cells modulate subsequently primed immune responses to unrelated antigens.. Cellular immunology. . 2003; 224(2): 74-85.
Kaufman, DL Murder mysteries in type 1 diabetes.. Nature medicine. . 2003; 9(2): 161-2.
Kaufman, DL Tisch, R Sarvetnick, N Chatenoud, L Harrison, LC Haskins, K Quinn, A Sercarz, E Singh, B von Herrath, M Wegmann, D Wen, L Zekzer, D Report from the 1st International NOD Mouse T-Cell Workshop and the follow-up mini-workshop.. Diabetes. . 2001; 50(11): 2459-63.
Rocha, L Ondarza, R Kaufman, DL Antisense oligonucleotides to C-fos reduce postictal seizure susceptibility following fully kindled seizures in rats.. Neuroscience letters. . 1999; 268(3): 143-6.
Tian, J Kaufman, DL Attenuation of inducible Th2 immunity with autoimmune disease progression.. Journal of immunology (Baltimore, Md. : 1950) . 1998; 161(10): 5399-403.
Kranzler, HR Gelernter, J O'Malley, S Hernandez-Avila, CA Kaufman, D Association of alcohol or other drug dependence with alleles of the mu opioid receptor gene (OPRM1).. Alcoholism, clinical and experimental research. . 1998; 22(6): 1359-62.
Tian, J Olcott, AP Hanssen, LR Zekzer, D Middleton, B Kaufman, DL Infectious Th1 and Th2 autoimmunity in diabetes-prone mice.. Immunological reviews. . 1998; 164: 119-27.
Rocha, L Kaufman, DL In vivo administration of c-Fos antisense oligonucleotides accelerates amygdala kindling.. Neuroscience letters. . 1998; 241(2-3): 111-4.
Tian, J Lehmann, PV Kaufman, DL Determinant spreading of T helper cell 2 (Th2) responses to pancreatic islet autoantigens.. The Journal of experimental medicine. . 1997; 186(12): 2039-43.
Tian, J Clare-Salzler, M Herschenfeld, A Middleton, B Newman, D Mueller, R Arita, S Evans, C Atkinson, MA Mullen, Y Sarvetnick, N Tobin, AJ Lehmann, PV Kaufman, DL Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice.. Nature medicine. . 1996; 2(12): 1348-53.
Kaufman, DL Keith, DE Anton, B Tian, J Magendzo, K Newman, D Tran, TH Lee, DS Wen, C Xia, YR Characterization of the murine mu opioid receptor gene.. The Journal of biological chemistry. . 1995; 270(26): 15877-83.
Research Interest:

My laboratory is interested in; autoimmune disease (particularly Type I diabetes), islet transplantation and generation of insulin-producing cells by transdifferentiation, in vivo imaging, the role of MHCI in neurorepair, and Parkinson's disease. Part of our work centers on understanding the basis of autoimmune diseases (e.g., Type I diabetes) in animal models. We hope to obtain basic information on the autoimmune disease process and then use this to design novel therapeutics. We are pursuing several therapeutic strategies: A) Prevent the initiation of autoimmunity using protein administration or gene therapy to inactivate potentially dangerous T cells. B) If autoimmunity has arisen, delay disease progression by immunological, pharmacological or gene therapy approaches which inhibit autoreactive T cells. C) If extensive tissue destruction has resulted in overt disease, replace the damaged tissue through transplantation--which in the case of type I diabetes requires protecting islet transplants from immune rejection. As an alternative to transplanting foreign tissue, we are learning how to transdifferentiate autologous hepatocytes and stem cells into insulin-producing cells. We also seek to non-invasively image the insulin-producing cells in live animals. This will greatly aid studies of the diabetes disease process, evaluating the efficacy of interventive therapies and monitoring the survival of transplanted insulin-producing cells. Another project is focused on the recent finding that MHCI (a key immune system molecule that is involved in T cell selection and recognizing foreign invaders) is also involved in neurodevelopment. Aparently, MHCI is not only involved in T cell selection, but also plays a role in establishing and rejecting synaptic connections during neurodevelopment. We have found that transgenic mice which express neuronal MHCI are deficient in neuronal repair responses. As MHC I expression is up-regulated in many neuropathological conditions, treatments which limit the inhibitory effects of neuronal MHC I could have clinical utility. Finally, we are pursuing a vaccine approach to protect dopaminergic neurons in an animal model of Parkinson's disease. It appears that vaccine-induced immune responses can home to damaged areas in the CNS, alter the gene expression patterns of microglia, and have a neuroprotective effect.