23-167 Center for Health Sciences

Research Description:

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.

  • PhD, UCLA
  • Postdoc, Salk Institute

Tian J, Milddleton B, Kaufman DL. GABA administration prevents severe illness and death following coronavirus infection in mice. bioRxiv. 2020. Epub 2020/10/08. doi: 10.1101/2020.10.04.325423. PubMed PMID: 33024975; PMCID: PMC7536896.

Tian, J., Dang, H., O’Laco, KA, Song, M., Tiu, B-C, Gilles, S., Zakarian, C., Kaufman, DL. Homotaurine treatment enhances CD4+and CD8+Treg responses and synergizes with low-dose anti-CD3 to enhance diabetes remission in type 1 diabetic mice. ImmuoHorizons, 2019 Oct 21;3(10):498-510. doi: 10.4049/immunohorizons.1900019. PMID: 31636084

Tian, J., Dang, H., Karashchuk, N., Xu, I., Kaufman, DL. 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. J. Diab. Res., 2019 Feb 26;2019:5783545. doi: 10.1155/2019/5783545, 2019. PMID: 30937314

Yong, J., Tian, J., Dang, H., Wu, T-T., Atkinson, MA., Sun, R., Kaufman, DL. Increased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the Avyobesity-associated gene. Scientific Reports.Mar 12;9(1):4269. doi: 10.1038/s41598-019-38905-z, 2019. PMID: 30862859

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. Scientific ReportsNov 8;8(1):16555. doi: 10.1038/s41598-018-32733-3, 2018, PMID: 30410049