Site Search



Daniel Kaufman, Ph.D.

Work Email Address:
dkaufman@mednet.ucla.edu

Laboratory Address:
Laboratory
23-167 CHS
Los Angeles, CA 90095
UNITED STATES

Office Address:
Office
23-167 CHS
Los Angeles, CA 90095
UNITED STATES

Lab Number:
310-206-3350
Office Phone Number:
310-794-9664



Login to the Faculty Database

Department / Division Affiliations
Member, ACCESS Program: Dept. of Molecular & Medical Pharmacology, Brain Research Institute
Professor, Molecular & Medical Pharmacology
Member, Neuroscience IDP

Research Interest:

Parkinson’s disease, autism and schizophrenia, spinal cord injury

My lab performs studies in the fields of Parkinson’s disease, autism and schizophrenia, and spinal cord injury, as described below. Parkinson’s disease. Studies by several labs, including our own, have shown that a type of white blood cell called regulatory T cells (Tregs) can have neuroprotective effects in animal models of multiple sclerosis, traumatic brain injury, ALS and other neurodegenerative diseases. In many countries, infants receive a vaccine called “BCG” against childhood tuberculosis. BCG is a weakened relative of the bacteria that cause tuberculosis and leprosy. It is known that immunization with BCG induces T cells that can attack tuberculosis-causing bacteria, as well as Tregs. Because BCG is very safe for human use, we tested whether BCG immunization could have a beneficial effect in a mouse model of Parkinson’s disease. We published that BCG vaccination was indeed neuroprotective. In preparation for possible clinical trials, we want to study whether subsequent BCG immunizations continue to have neuroprotective effects, or could become ineffectual or deleterious, and to verify that the neuroprotection is conveyed by Tregs. We also want to screen different BCG strains for their ability to induce Tregs. Autism and schizophrenia. There is growing epidemiological evidence that infections during pregnancy are associated with higher incidences of autism and schizophrenia in offspring. It is also thought that abnormalities in the expression of genes involved in neuronal development are leading candidates for causes of autism and schizophrenia. We have been studying a molecule called major histocompatibility complex I (MHCI). In the immune system, MHCI plays a key role in identifying foreign invaders, and they are the proteins that clinicians try to match when performing any type of tissue transplantation. Recent studies indicate that MHCI also plays a key role in neurodevelopment. In several reported studies, we have shown that a small increase in neuronal MHCI expression during mouse fetal development leads to aberrations in neuronal outgrowth and synapse formation. Notably, neuronal MHCI expression levels increase in response to infections, which may explain the association between infections during pregnancy and increased risk for autism and schizophrenia in offspring. We are interested in further exploring the role of MHCI during neurodevelopment and how changes in its expression during neurodevelopment may change the offspring’s behaviors. Spinal cord injury. In collaboration with Dr. Reggie Edgerton, we have reported that transgenic mice with increased MHCI levels on their neurons have a greater ability to recover locomotor function after a spinal cord injury. To translate these observations into a potential treatment for human spinal cord injury, we are interested in performing gene therapy to increase MHCI levels in the spinal cord neurons of which mice with a recent spinal cord injury. If successful, this gene therapy could then be extended to humans with recent spinal cord injuries.

Publications:

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: .
Download
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: .
Download
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 .
Download
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.
Download
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.
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.
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.
Laćan 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 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 β-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 ß-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 γ-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 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.
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 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.
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.