Daniel L. Kaufman, Ph.D.
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Office Phone Number:
Los Angeles, CA 90095
Los Angeles, CA 90095
|Professor, Molecular & Medical Pharmacology|
|Member, Brain Research Institute, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, Molecular Pharmacology GPB Home Area, Neuroscience GPB Home Area|
My lab performs studies in the fields of diabetes, multiple sclerosis, and Parkinson’s disease. We are interested in understanding their disease mechanisms and testing novel therapeutics in mouse models that could potentially be translated to clinical use. A number of the diagnostics and therapeutics for type 1 diabetes (Juvenile diabetes) that our lab helped to develop are now in clinical use or are being tested in clinical trials. Most recently, we are interested in how receptors on immune cells for the amino acid GABA can modulate their function. Using mouse models, we have shown that activation of GABA receptors on immune cells can inhibit type 1 diabetes, rheumatoid arthritis, as well as type 2 diabetes. In addition, the insulin-producing ß-cells of the pancreas also express GABA receptors. We, and others, have shown that activating these ß-cell GABA receptors can promote the survival and replication of the ß-cells. We are interested in combining GABA treatment with other immune modulators in order to preserve and expand ß-cells in the context of autoimmunity (as occurs in type 1 diabetes). Based on GABA’s ability to safely inhibit autoreactivity, we have also begun studies in mice of new GABA-receptor modulating drugs that can pass through the blood brain barrier and inhibit autoreactivity as potential treatments for multiple sclerosis. Finally, we are interested in how induced immune responses can inhibit neurodegeneration in a mouse model of Parkinson’s disease.
Tian J, Dang H, Middleton B, Kaufman DL. Clinically applicable GABA receptor positive allosteric modulators promote ß-cell replication. Scientific Reports 2017; .
Jide Tian, Hoa Dang, Angela Hu, Willem Xu, and Daniel L. Kaufman Repurposing lesogaberan to promote human islet-cell survival and ß-cell replication. J. Diab. Res 2017; in press: .
Tian, J., Dang, H., Nguyen, A.V., Chen, Z, Kaufman, DL Combined therapy with GABA and proinsulin/alum acts synergistically to restore long-term normoglycemia by modulating T cell autoimmunity and promoting ß-cell replication in newly diabetic NOD mice. Diabetes 2014; 63: 3128-3134.
LaÄan Goran, Dang Hoa, Middleton Blake, Horwitz Marcus A, Tian Jide, Melega William P, Kaufman Daniel L Bacillus Calmette-Guerin vaccine-mediated neuroprotection is associated with regulatory T-cell induction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Journal of neuroscience research. 2013; .
Tian Jide, Dang Hoa, Chen Zheying, Guan Alice, Jin Yingli, Atkinson Mark A, Kaufman Daniel L GABA regulates both the survival and replication of human ss-cells. Diabetes. 2013; .
Bilousova Tina, Dang Hoa, Xu Willem, Gustafson Sarah, Jin Yingli, Wickramasinghe Lalinda, Won Tony, Bobarnac Gabriela, Middleton Blake, Tian Jide, Kaufman Daniel L Major histocompatibility complex class I molecules modulate embryonic neuritogenesis and neuronal polarization. Journal of Neuroimmunology. 2012; 247(1-2): 1-8.
Tian Jide, Yong Jing, Dang Hoa, Kaufman Daniel L Oral GABA treatment downregulates inflammatory responses in a mouse model of rheumatoid arthritis. Autoimmunity. 2011; 44(6): 465-70.
Washburn, L.R., Zekzer, D., Eitan, S., Lu, Y., Dang, H., Middleton, B., Evans, C.J., Tian, J., Kaufman, D.L. A potential role for shed soluble major histocompatibility class I molecules as modulators of neurite outgrowth. . PLoS ONE 2011; e18439: .
Yong, J., Lacan, G., Dang, H., Hsieh, T., Middleton, B., Wasserfall, C., Tian, J., Melega, W.P., Kaufman, D.L. BCG vaccine-induced neuroprotection in a mouse model of Parkinson's Disease. PLoS ONE 2011; 6(1):e16610. PMCID: PMC3031604: .
Tian, J., Dang, H., Kaufman D.L Combining Antigen-Based Therapy with GABA Treatment Synergistically Prolongs Survival of Transplanted ß-Cells in Diabetic NOD Mice. PLoS ONE 2011; e25337: .
Wu ZP, Washburn L, Bilousova TV, Boudzinskaia M, Escande-Beillard N, Querubin J, Dang H, Xie CW, Tian J, Kaufman DL Enhanced neuronal expression of major histocompatibility complex class I leads to aberrations in neurodevelopment and neurorepair. J Neuroimmunol 2011; 232: 8-16.
Wu ZP, Bilousova T, Dang H, Hsieh T, Tian J, Kaufman DL Major histocompatibility complex class I-mediated inhibition of neurite outgrowth from peripheral nerves. Immunol Lett 2011; 135: 118-123.
Yong, J., Rasooly, J., Dang, H,, Lu, Y., Middleton, B., Zhang, Z., Hon, L., Namavari, M., Stout, D., Atkinson, M.A., Tian, J., Gambhir, S.S., Kaufman, D.L Multimodality Imaging of ß-cells in Mouse Models of Type I and II Diabetes. Diabetes 2011; 60: 1383-1392 .
Tian, J., Young, J, Dang H., and Kaufman DL. Oral GABA treatment down-regulates inflammatory responses in a mouse model of rheumatoid arthritis. Autoimmunity 2011; 44 : 465-470.
Tian, J., Dang, H.N., Yong, J., Chui W-S, Dizon, M.P.G., Yaw, C.K.Y. Kaufman, D.L Oral Treatment with γ-Aminobutyric Acid Improves Glucose Tolerance and Insulin Sensitivity by Inhibiting Inflammation in High Fat Diet-Fed Mice. PLoS ONE 2011; e25338: .
Joseph, S.M., Wu, Z-P, Zdunowski, S., Middleton, B., Boudzinskaia, M, Wong, B., Ali, N., Zhong, H., Yong, J., Washburn, L., Escande-Beillard, N., Dang, N., Edgerton, V.R., Tillakaratne. N.J.K., Kaufman, D.L., Transgenic mice with enhanced neuronal MHC class I expression recover locomotor function better after spinal cord injury. J Neurosci Res 2011; 89: 365-372.
Washburn Lorraine R, Zekzer Dan, Eitan Shoshana, Lu Yuxin, Dang Hoa, Middleton Blake, Evans Christopher J, Tian Jide, Kaufman Daniel L A potential role for shed soluble major histocompatibility class I molecules as modulators of neurite outgrowth. PloS one. 2011; 6(3): e18439.
Yong Jing, Rasooly Julia, Dang Hoa, Lu Yuxin, Middleton Blake, Zhang Zesong, Hon Larry, Namavari Mohammad, Stout David B, Atkinson Mark A, Tian Jide, Gambhir Sanjiv Sam, Kaufman Daniel L Multimodality imaging of Î²-cells in mouse models of type 1 and 2 diabetes. Diabetes. 2011; 60(5): 1383-92.
Yong Jing, Lacan Goran, Dang Hoa, Hsieh Terry, Middleton Blake, Wasserfall Clive, Tian Jide, Melega William P, Kaufman Daniel L BCG vaccine-induced neuroprotection in a mouse model of Parkinson's disease. PloS one. 2011; 6(1): e16610.
Tian Jide, Dang Hoa, Kaufman Daniel L Combining antigen-based therapy with GABA treatment synergistically prolongs survival of transplanted Ã-cells in diabetic NOD mice. PloS one. 2011; 6(9): e25337.
Wu Zhongqi-Phyllis, Washburn Lorraine, Bilousova Tina V, Boudzinskaia Maia, Escande-Beillard Nathalie, Querubin Jyes, Dang Hoa, Xie Cui-Wei, Tian Jide, Kaufman Daniel L Enhanced neuronal expression of major histocompatibility complex class I leads to aberrations in neurodevelopment and neurorepair. Journal of neuroimmunology. 2011; 232(1-2): 8-16.
Wu Zhongqi-Phyllis, Bilousova Tina, Escande-Beillard Nathalie, Dang Hoa, Hsieh Terry, Tian Jide, Kaufman Daniel L Major histocompatibility complex class I-mediated inhibition of neurite outgrowth from peripheral nerves. Immunology letters. 2011; 135(1-2): 118-23.
Tian Jide, Dang Hoa N, Yong Jing, Chui Wing-Sheung, Dizon Matthew P G, Yaw Catherine K Y, Kaufman Daniel L Oral treatment with Î³-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice. PloS one. 2011; 6(9): e25338.
Joseph M Selvan, Bilousova Tina, Zdunowski Sharon, Wu Zhongqi-Phyllis, Middleton Blake, Boudzinskaia Maia, Wong Bonnie, Ali Noore, Zhong Hui, Yong Jing, Washburn Lorraine, Escande-Beillard Nathalie, Dang Hoa, Edgerton V Reggie, Tillakaratne Niranjala J K, Kaufman Daniel L Transgenic mice with enhanced neuronal major histocompatibility complex class I expression recover locomotor function better after spinal cord injury. Journal of neuroscience research. 2011; 89(3): 365-72.
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; 184: 816-823.
Escande-Beillard Nathalie, Washburn Lorraine, Zekzer Dan, Wu Zhongqi-Phyllis, Eitan Shoshy, Ivkovic Sonja, Lu Yuxin, Dang Hoa, Middleton Blake, Bilousova Tina V, Yoshimura Yoshitaka, Evans Christopher J, Joyce Sebastian, Tian Jide, Kaufman Daniel L Neurons preferentially respond to self-MHC class I allele products regardless of peptide presented. Journal of immunology (Baltimore, Md. : 1950). 2010; 184(2): 816-23.
Tian Jide, Dang Hoa, von Boehmer Harald, Jaeckel Elmar, Kaufman Daniel L Transgenically induced GAD tolerance curtails the development of early beta-cell autoreactivities but causes the subsequent development of supernormal autoreactivities to other beta-cell antigens. Diabetes. 2009; 58(12): 2843-50.
Tian Jide, Kaufman Daniel L Antigen-based therapy for the treatment of type 1 diabetes. Diabetes. 2009; 58(9): 1939-46.
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.
Lu Yuxin, Dang Hoa, Middleton Blake, Campbell-Thompson Martha, Atkinson Mark A, Gambhir Sanjiv Sam, Tian Jide, Kaufman Daniel L 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.
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., 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.
Tian Jide, Zekzer Dan, Lu Yuxin, Dang Hoa, Kaufman Daniel L B cells are crucial for determinant spreading of T cell autoimmunity among beta cell antigens in diabetes-prone nonobese diabetic mice. Journal of immunology (Baltimore, Md. : 1950). 2006; 176(4): 2654-61.
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 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.
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, 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.
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.
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 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 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.
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.
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.
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.
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.
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.
Tian, J., Dang, H., Wallner, M., Olsen R., and Kaufman D.L. Homotaurine, a safe blood-brain barrier permeable GABAA-R-specific agonist, ameliorates disease in mouse models of multiple sclerosis. Sci. Reports in press 2018; .