Daniel L Kaufman

Professor, Molecular and Medical Pharmacology, University of California Los Angeles

UC Profile
Daniel Kaufman website

Immunotherapeutics for disease Research in our lab is focused on 1) understanding the basis for immune-mediated disorders and 2) developing new therapeutics in preclinical models to help alleviate these disorders. A diagnostic test and two therapeutics for type 1 diabetes that our lab helped to develop are now in clinical use or are being tested in clinical trials. Second, we have demonstrated that immune cells express receptors for the neurotransmitter GABA and that the activation of these receptors can safely inhibit their inflammatory activities. Based on their anti-inflammatory actions, we have shown that the administration of GABA receptor agonists can inhibit or reverse type 1 diabetes, rheumatoid arthritis, and multiple sclerosis in mouse models. During the COVID-19 pandemic, we pivoted our work to study whether GABA treatment could be repurposed to help treat the excessive immune responses that cause severe illness in COVID-19 patients. We showed that GABA treatment effectively prevents severe disease and death in two different mouse models of COVID-19. Most recently, we have begun to study how GABA released from glioblastomas may inhibit local anti-tumor responses. Our future research will continue to develop ways to help modulate the immune system to ameliorate human diseases.

Interests

insulin, GABA-receptor, GABA, glioblastoma, neuroinflammation, SARS-CoV-2, COVID-19, type 1 diabetes (T1D), multiple sclerosis, glutamic acid decarboxylase, Parkinson's disease, long-COVID, ß-cell, autoimmune disease

Publications

  1. Tian J, Kaufman DL. The GABA and GABA-Receptor System in Inflammation, Anti-Tumor Immune Responses, and COVID-19.. Biomedicines, 2023.
  2. Tian J, Dillion BJ, Henley J, Comai L, Kaufman DL. A GABA-receptor agonist reduces pneumonitis severity, viral load, and death rate in SARS-CoV-2-infected mice.. Frontiers in immunology, 2022.
  3. Tian J, Song M, Kaufman DL. Designing Personalized Antigen-Specific Immunotherapies for Autoimmune Diseases-The Case for Using Ignored Target Cell Antigen Determinants.. Cells, 2022.
  4. Song M, Tian J, Middleton B, Nguyen CQ, Kaufman DL. GABA Administration Ameliorates Sjogren's Syndrome in Two Different Mouse Models.. Biomedicines, 2022.
  5. Kaufman DL. GABA molecules made by B cells can dampen antitumour responses.. Nature, 2021.
  6. Tian J, Middleton B, Kaufman DL. GABAA-Receptor Agonists Limit Pneumonitis and Death in Murine Coronavirus-Infected Mice.. Viruses, 2021.
  7. Tian J, Song M, Kaufman DL. Homotaurine limits the spreading of T cell autoreactivity within the CNS and ameliorates disease in a model of multiple sclerosis.. Scientific reports, 2021.
  8. Tian J, Middleton B, Lee VS, Park HW, Zhang Z, Kim B, Lowe C, Nguyen N, Liu H, Beyer RS, Chao HW, Chen R, Mai D, O'Laco KA, Song M, Kaufman DL. GABAB-Receptor Agonist-Based Immunotherapy for Type 1 Diabetes in NOD Mice.. Biomedicines, 2021.
  9. Tian J, Middleton B, Kaufman DL. GABA administration prevents severe illness and death following coronavirus infection in mice.. bioRxiv : the preprint server for biology, 2020.
  10. Tian J, Dang H, O'Laco KA, Song M, Tiu BC, Gilles S, Zakarian C, Kaufman DL. Homotaurine Treatment Enhances CD4+ and CD8+ Regulatory T Cell Responses and Synergizes with Low-Dose Anti-CD3 to Enhance Diabetes Remission in Type 1 Diabetic Mice.. ImmunoHorizons, 2019.
  11. Yong J, Tian J, Dang H, Wu TT, Atkinson MA, Sun R, Kaufman DL. Increased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the Avy obesity-associated gene.. Scientific reports, 2019.
  12. Tian J, Dang H, Karashchuk N, Xu I, Kaufman DL. A Clinically Applicable Positive Allosteric Modulator of GABA Receptors Promotes Human β-Cell Replication and Survival as well as GABA's Ability to Inhibit Inflammatory T Cells.. Journal of diabetes research, 2019.
  13. Tian J, Dang H, Wallner M, Olsen R, Kaufman DL. Homotaurine, a safe blood-brain barrier permeable GABAA-R-specific agonist, ameliorates disease in mouse models of multiple sclerosis.. Scientific reports, 2018.
  14. Marya NB, Jawaid S, Foley A, Han S, Patel K, Maranda L, Kaufman D, Bhattacharya K, Marshall C, Tennyson J, Cave DR. A randomized controlled trial comparing efficacy of early video capsule endoscopy with standard of care in the approach to nonhematemesis GI bleeding (with videos).. Gastrointestinal endoscopy, 2018.
  15. Tian J, Dang H, Hu A, Xu W, Kaufman DL. Repurposing Lesogaberan to Promote Human Islet Cell Survival and β-Cell Replication.. Journal of diabetes research, 2017.
  16. Tian J, Dang H, Middleton B, Kaufman DL. Clinically applicable GABA receptor positive allosteric modulators promote ß-cell replication.. Scientific reports, 2017.
  17. Tian J, Dang H, Nguyen AV, 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 β-cell replication in newly diabetic NOD mice.. Diabetes, 2014.
  18. Tian J, Dang H, Chen Z, Guan A, Jin Y, Atkinson MA, Kaufman DL. γ-Aminobutyric acid regulates both the survival and replication of human β-cells.. Diabetes, 2013.
  19. Lacan G, Dang H, Middleton B, Horwitz MA, Tian J, Melega WP, Kaufman DL. 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.
  20. Bilousova T, Dang H, Xu W, Gustafson S, Jin Y, Wickramasinghe L, Won T, Bobarnac G, Middleton B, Tian J, Kaufman DL. Major histocompatibility complex class I molecules modulate embryonic neuritogenesis and neuronal polarization.. Journal of neuroimmunology, 2012.
  21. Tian J, Dang H, Kaufman DL. Combining antigen-based therapy with GABA treatment synergistically prolongs survival of transplanted ß-cells in diabetic NOD mice.. PloS one, 2011.
  22. Tian J, Dang HN, Yong J, Chui WS, Dizon MP, Yaw CK, Kaufman DL. Oral treatment with γ-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice.. PloS one, 2011.
  23. Tian J, Yong J, Dang H, Kaufman DL. Oral GABA treatment downregulates inflammatory responses in a mouse model of rheumatoid arthritis.. Autoimmunity, 2011.
  24. Washburn LR, Zekzer D, Eitan S, Lu Y, Dang H, Middleton B, Evans CJ, Tian J, Kaufman DL. A potential role for shed soluble major histocompatibility class I molecules as modulators of neurite outgrowth.. PloS one, 2011.
  25. Yong J, Rasooly J, Dang H, Lu Y, Middleton B, Zhang Z, Hon L, Namavari M, Stout DB, Atkinson MA, Tian J, Gambhir SS, Kaufman DL. Multimodality imaging of β-cells in mouse models of type 1 and 2 diabetes.. Diabetes, 2011.
  26. Yong J, Lacan G, Dang H, Hsieh T, Middleton B, Wasserfall C, Tian J, Melega WP, Kaufman DL. BCG vaccine-induced neuroprotection in a mouse model of Parkinson's disease.. PloS one, 2011.
  27. Joseph MS, Bilousova T, Zdunowski S, Wu ZP, Middleton B, Boudzinskaia M, Wong B, Ali N, Zhong H, Yong J, Washburn L, Escande-Beillard N, Dang H, Edgerton VR, Tillakaratne NJ, Kaufman DL. Transgenic mice with enhanced neuronal major histocompatibility complex class I expression recover locomotor function better after spinal cord injury.. Journal of neuroscience research, 2010.
  28. Wu ZP, Bilousova T, Escande-Beillard N, Dang H, Hsieh T, Tian J, Kaufman DL. Major histocompatibility complex class I-mediated inhibition of neurite outgrowth from peripheral nerves.. Immunology letters, 2010.
  29. 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.. Journal of neuroimmunology, 2010.
  30. Escande-Beillard N, Washburn L, Zekzer D, Wu ZP, Eitan S, Ivkovic S, Lu Y, Dang H, Middleton B, Bilousova TV, Yoshimura Y, Evans CJ, Joyce S, Tian J, Kaufman DL. Neurons preferentially respond to self-MHC class I allele products regardless of peptide presented.. Journal of immunology (Baltimore, Md. : 1950), 2009.
  31. Tian J, Dang H, von Boehmer H, Jaeckel E, Kaufman DL. 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.
  32. Tian J, Kaufman DL. Antigen-based therapy for the treatment of type 1 diabetes.. Diabetes, 2009.
  33. Chen L, Zhang Y, Kong X, Lan E, Huang Z, Peng S, Kaufman DL, Tian J. Design, synthesis, and antihepatocellular carcinoma activity of nitric oxide releasing derivatives of oleanolic acid.. Journal of medicinal chemistry, 2008.
  34. Washburn LR, Dang H, Tian J, Kaufman DL. The postnatal maternal environment influences diabetes development in nonobese diabetic mice.. Journal of autoimmunity, 2007.
  35. 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.
  36. Lu Y, Dang H, Middleton B, Zhang Z, Washburn L, Stout DB, Campbell-Thompson M, Atkinson MA, Phelps M, Gambhir SS, Tian J, Kaufman DL. Noninvasive imaging of islet grafts using positron-emission tomography.. Proceedings of the National Academy of Sciences of the United States of America, 2006.
  37. Tian J, Zekzer D, Lu Y, Dang H, Kaufman DL. 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.
  38. Olcott AP, Tian J, Walker V, Dang H, Middleton B, Adorini L, Washburn L, Kaufman DL. Antigen-based therapies using ignored determinants of beta cell antigens can more effectively inhibit late-stage autoimmune disease in diabetes-prone mice.. Journal of immunology (Baltimore, Md. : 1950), 2005.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. Kaufman DL. Murder mysteries in type 1 diabetes.. Nature medicine, 2003.
  44. Tian J, Olcott AP, Kaufman DL. Antigen-based immunotherapy drives the precocious development of autoimmunity.. Journal of immunology (Baltimore, Md. : 1950), 2002.
  45. 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.
  46. Tian J, Zekzer D, Hanssen L, Lu Y, Olcott A, Kaufman DL. Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent autoimmune diabetes in nonobese diabetic mice.. Journal of immunology (Baltimore, Md. : 1950), 2001.
  47. Tian J, Gregori S, Adorini L, Kaufman DL. The frequency of high avidity T cells determines the hierarchy of determinant spreading.. Journal of immunology (Baltimore, Md. : 1950), 2001.
  48. Tian J, Chau C, Hales TG, Kaufman DL. GABA(A) receptors mediate inhibition of T cell responses.. Journal of neuroimmunology, 1999.
  49. Tian J, Kaufman DL. Attenuation of inducible Th2 immunity with autoimmune disease progression.. Journal of immunology (Baltimore, Md. : 1950), 1998.
  50. Tian J, Olcott AP, Hanssen LR, Zekzer D, Middleton B, Kaufman DL. Infectious Th1 and Th2 autoimmunity in diabetes-prone mice.. Immunological reviews, 1998.
  51. Tian J, Chau C, Kaufman DL. Insulin selectively primes Th2 responses and induces regulatory tolerance to insulin in pre-diabetic mice.. Diabetologia, 1998.
  52. 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.
  53. 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.
  54. Tian J, Atkinson MA, Clare-Salzler M, Herschenfeld A, Forsthuber T, Lehmann PV, Kaufman DL. Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes.. The Journal of experimental medicine, 1996.
  55. Miotto K, Kaufman D, Anton B, Keith DE, Evans CJ. Human opioid receptors: chromosomal mapping and mRNA localization.. NIDA research monograph, 1996.
  56. Atkinson MA, Bowman MA, Campbell L, Darrow BL, Kaufman DL, Maclaren NK. Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes.. The Journal of clinical investigation, 1994.
  57. Tian J, Lehmann PV, Kaufman DL. T cell cross-reactivity between coxsackievirus and glutamate decarboxylase is associated with a murine diabetes susceptibility allele.. The Journal of experimental medicine, 1994.
  58. Esclapez M, Tillakaratne NJ, Kaufman DL, Tobin AJ, Houser CR. Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 1994.
  59. Kaufman DL, Xia YR, Keith DE, Newman D, Evans CJ, Lusis AJ. Localization of the delta-opioid receptor gene to mouse chromosome 4 by linkage analysis.. Genomics, 1994.
  60. Vardi N, Kaufman DL, Sterling P. Horizontal cells in cat and monkey retina express different isoforms of glutamic acid decarboxylase.. Visual neuroscience, 1994.
  61. Kaufman DL, Clare-Salzler M, Tian J, Forsthuber T, Ting GS, Robinson P, Atkinson MA, Sercarz EE, Tobin AJ, Lehmann PV. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes.. Nature, 1993.
  62. Kaufman DL, Tobin AJ. Glutamate decarboxylases and autoimmunity in insulin-dependent diabetes.. Trends in pharmacological sciences, 1993.
  63. Atkinson MA, Kaufman DL, Newman D, Tobin AJ, Maclaren NK. Islet cell cytoplasmic autoantibody reactivity to glutamate decarboxylase in insulin-dependent diabetes.. The Journal of clinical investigation, 1993.
  64. Gottschalk ME, Schatz DA, Clare-Salzler M, Kaufman DL, Ting GS, Geffner ME. Permanent diabetes without serological evidence of autoimmunity after transient neonatal diabetes.. Diabetes care, 1992.
  65. Bu DF, Erlander MG, Hitz BC, Tillakaratne NJ, Kaufman DL, Wagner-McPherson CB, Evans GA, Tobin AJ. Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene.. Proceedings of the National Academy of Sciences of the United States of America, 1992.
  66. Atkinson MA, Kaufman DL, Campbell L, Gibbs KA, Shah SC, Bu DF, Erlander MG, Tobin AJ, Maclaren NK. Response of peripheral-blood mononuclear cells to glutamate decarboxylase in insulin-dependent diabetes.. Lancet (London, England), 1992.
  67. Tobin AJ, Brecha N, Chiang MY, Endo S, Erlander MG, Feldblum S, Houser CR, Kaufman DL, Khrestchatistky M, MacLennan AJ. Alternative forms of GAD and GABAA receptors.. Advances in biochemical psychopharmacology, 1992.
  68. Kaufman DL, Erlander MG, Clare-Salzler M, Atkinson MA, Maclaren NK, Tobin AJ. Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus.. The Journal of clinical investigation, 1992.
  69. Clare-Salzler MJ, Tobin AJ, Kaufman DL. Glutamate decarboxylase: an autoantigen in IDDM.. Diabetes care, 1992.
  70. Gonzales C, Kaufman DL, Tobin AJ, Chesselet MF. Distribution of glutamic acid decarboxylase (Mr 67,000) in the basal ganglia of the rat: an immunohistochemical study with a selective cDNA-generated polyclonal antibody.. Journal of neurocytology, 1991.
  71. Kaufman DL, Houser CR, Tobin AJ. Two forms of the gamma-aminobutyric acid synthetic enzyme glutamate decarboxylase have distinct intraneuronal distributions and cofactor interactions.. Journal of neurochemistry, 1991.
  72. Kaufman DL, Ramesh V, McClatchey AI, Menkes JH, Tobin AJ. Detection of point mutations associated with genetic diseases by an exon scanning technique.. Genomics, 1990.
  73. McClatchey AI, Kaufman DL, Berson EL, Tobin AJ, Shih VE, Gusella JF, Ramesh V. Splicing defect at the ornithine aminotransferase (OAT) locus in gyrate atrophy.. American journal of human genetics, 1990.
  74. Kaufman DL, Evans GA. Restriction endonuclease cleavage at the termini of PCR products.. BioTechniques, 1990.
  75. Kobayashi Y, Kaufman DL, Tobin AJ. Glutamic acid decarboxylase cDNA: nucleotide sequence encoding an enzymatically active fusion protein.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 1987.
  76. Sparkes RS, Klisak I, Kaufman D, Mohandas T, Tobin AJ, McGinnis JF. Assignment of the rhodopsin gene to human chromosome three, region 3q21-3q24 by in situ hybridization studies.. Current eye research, 1986.
  77. Wuenschell CW, Fisher RS, Kaufman DL, Tobin AJ. In situ hybridization to localize mRNA encoding the neurotransmitter synthetic enzyme glutamate decarboxylase in mouse cerebellum.. Proceedings of the National Academy of Sciences of the United States of America, 1986.
  78. Sparkes RS, Mohandas T, Newman SL, Heinzmann C, Kaufman D, Zollman S, Leveille PJ, Tobin AJ, McGinnis JF. Assignment of the rhodopsin gene to human chromosome 3.. Investigative ophthalmology & visual science, 1986.
  79. Kaufman DL, McGinnis JF, Krieger NR, Tobin AJ. Brain glutamate decarboxylase cloned in lambda gt-11: fusion protein produces gamma-aminobutyric acid.. Science (New York, N.Y.), 1986.
  80. Breakefield XO, Bressman SB, Kramer PL, Ozelius L, Moskowitz C, Tanzi R, Brin MF, Hobbs W, Kaufman D, Tobin A. Linkage analysis in a family with dominantly inherited torsion dystonia: exclusion of the pro-opiomelanocortin and glutamic acid decarboxylase genes and other chromosomal regions using DNA polymorphisms.. Journal of neurogenetics, 1986.