Daniel Kaufman, Ph.D.

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Work Titles
UCLA Professor, Molecular & Medical Pharmacology Member, Brain Research Institute Member, Immunity, Microbes & Molecular Pathogenesis GPB Home Area Member, Molecular Pharmacology GPB Home Area Member, Neuroscience GPB Home Area
Education:
Degrees:
Ph.D.

Contact Information:

Work Email Address:

dkaufman@mednet.ucla.edu


Website:

https://people.healthsciences.ucla.edu/institution/personnel?personnel_id=45958

Lab Number:

310-206-3350

Office Phone Number:

310-794-9664

Laboratory Address:

Laboratory
Dept. Molecular & Medical Pharmacology, Center for Health Science room 23-167
David Geffen School of Medicine at UCLA
Los Angeles, CA 90095


Office Address:

Office
23-167 Center for Health Science
Dept. of Molecular & Medical Pharmacology
David Geffen School of Medicine at UCLA
90095-1735
Los Angeles, CA 90095


Research Interest:

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. Most recently, we have 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 have shown that GABA treatment very effectively prevents severe disease and death in a mouse model of COVID-19. Our future research will continue to develop ways to help modulate dysregulated immune responses in human diseases.

Publications:

A selected list of publications:

Jide Tian, Blake Middleton, Daniel L Kaufman   GABA A-Receptor Agonists Limit Pneumonitis and Death in Murine Coronavirus-Infected Mice, Viruses, 2021; .
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Jide Tian, Blake Middleton, and Daniel L. Kaufman   GABA administration limits viral replication and pneumonitis in a mouse model of COVID-19, BioRxiv, 2021; https://www.biorxiv.org/content/10.1101/2021.02.09.430446v2: .
Kaufman Daniel L   GABA molecules made by B cells can dampen antitumour responses Nature, 2021; 599(7885): 374-376.
Tian Jide, Milddleton Blake, Kaufman Daniel L   GABA administration prevents severe illness and death following coronavirus infection in mice bioRxiv : the preprint server for biology, 2020; https://doi.org/10.1101/2020.10.04.325423: .
Tian Jide, Dang Hoa, Karashchuk Nataliya, Xu Irvin, Kaufman Daniel L   A clinically applicable positive allosteric modulator of GABA receptors promotes human ß-cell replication and survival as well as GABA’s ability to inhibit inflammatory T cells. Journal of diabetes research, 2019; 2019(1): 5783545.
Tian Jide, Dang Hoa, O'Laco Karen Anne, Song Min, Tiu Bryan-Clement, Gilles Spencer, Zakarian Christina, Kaufman Daniel L   Homotaurine treatment enhances CD4+ and CD8+ Treg responses and synergizes with low-dose anti-CD3 to enhance diabetes remission in type 1 diabetic mice ImmunoHorizons, 2019; 3(10): 498-510.
Yong Jing, Tian Jide, Dang Hoa, Wu Ting-Ting, Atkinson Mark A, Sun Ren, Kaufman Daniel L   Increased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the Avy obesity-associated gene Scientific reports, 2019; 9(1): 4269.
Tian Jide, Dang Hoa, Wallner Martin, Olsen Richard, Kaufman Daniel L   Homotaurine, a safe blood-brain barrier permeable GABAA-R-specific agonist, ameliorates disease in mouse models of multiple sclerosis Scientific Reports, 2018; 8(1): 16555.
Tian J, Dang H, Middleton B, Kaufman DL.   Clinically applicable GABA receptor positive allosteric modulators promote ß-cell replication, Scientific Reports, 2017; .
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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; .
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.
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.
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: .
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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, 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: .
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, 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: .
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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 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 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 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.
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.
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 .
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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.
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.
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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.
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: .
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, 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.
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.
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 Jide, Kaufman Daniel L   Antigen-based therapy for the treatment of type 1 diabetes Diabetes, 2009; 58(9): 1939-46.
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, 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.
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.
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.
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.
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 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.
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, 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.
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.
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.
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, et al.   GABA-A receptors mediate inhbition of T cell responses, J. Neuroimmunology, 1999; 96: 21-28.
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 Kaufman, DL   Attenuation of inducible Th2 immunity with autoimmune disease progression Journal of immunology (Baltimore, Md. : 1950) , 1998; 161(10): 5399-403.
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 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.
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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.
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.
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 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.
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 Jide, Song Min, Kaufman Daniel L   Homotaurine limits the spreading of T cell autoreactivity within the CNS and ameliorates disease in a model of multiple sclerosis Scientific reports, 2021; 11(1): 5402.
Song Min, Tian Jide, Middleton Blake, Nguyen Cuong Q, Kaufman Daniel L   GABA Administration Ameliorates Sjogren's Syndrome in Two Different Mouse Models Biomedicines, 2022; 10(1): 1001-1010.
Tian Jide, Song Min, Kaufman Daniel L   Designing Personalized Antigen-Specific Immunotherapies for Autoimmune Diseases-The Case for Using Ignored Target Cell Antigen Determinants Cells, 2022; 11(7): 31348221091951.
Tian J, Dillion B, Henley J, Comai L, Kaufman DL.   GABA-receptors are a new druggable target for limiting disease severity, lung viral load, and death in SARS-CoV-2 infected mice, BioRxiv, 2022; .
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