Daniel L Kaufman
Professor, Molecular and Medical Pharmacology, University of California Los Angeles
dkaufman@mednet.ucla.edu
310-206-3350
Dept. Molecular & Medical Pharmacology, Center for Health Science room 23-167
David Geffen School of Medicine at UCLA
Los Angeles, CA 90095
Office Address:
23-167 Center for Health Science
Dept. of Molecular & Medical Pharmacology
David Geffen School of Medicine at UCLA
90095-1735
Los Angeles, CA 90095
Office Phone Number:
310-794-9664
Affiliations
Member, Brain Research Institute, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, Molecular Pharmacology GPB Home Area, Neuroscience GPB Home Area
Research Interests
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
- 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.
- Song M, Tian J, Middleton B, Nguyen CQ, Kaufman DL. GABA Administration Ameliorates Sjogren's Syndrome in Two Different Mouse Models.. Biomedicines, 2022.
- Kaufman DL. GABA molecules made by B cells can dampen antitumour responses.. Nature, 2021.
- Tian J, Middleton B, Kaufman DL. GABAA-Receptor Agonists Limit Pneumonitis and Death in Murine Coronavirus-Infected Mice.. Viruses, 2021.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Kaufman D, Leslie G, Marya N, Han S, Gillespie W, Holzwanger E, Leslie R, Cave D. Small Intestinal Angioectasia: Characterization, Risk Factors, and Rebleeding.. Journal of clinical gastroenterology, 2017.
- Tian J, Dang H, Middleton B, Kaufman DL. Clinically applicable GABA receptor positive allosteric modulators promote ß-cell replication.. Scientific reports, 2017.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Tian J, Yong J, Dang H, Kaufman DL. Oral GABA treatment downregulates inflammatory responses in a mouse model of rheumatoid arthritis.. Autoimmunity, 2011.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Tian J, Kaufman DL. Antigen-based therapy for the treatment of type 1 diabetes.. Diabetes, 2009.
- 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.
- Kaufman D, Banerji MA, Shorman I, Smith EL, Coplan JD, Rosenblum LA, Kral JG. Early-life stress and the development of obesity and insulin resistance in juvenile bonnet macaques.. Diabetes, 2007.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Kaufman DL. Murder mysteries in type 1 diabetes.. Nature medicine, 2003.
- Tian J, Olcott AP, Kaufman DL. Antigen-based immunotherapy drives the precocious development of autoimmunity.. Journal of immunology (Baltimore, Md. : 1950), 2002.
- 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.