Dean Tantin

Our research emphasis is stem cells and the activities that endow cells with stem-like properties such as long life, homing to specific niches, self-renewal, and the ability to rapidly induce cohorts of silent but poised genes in response to external cues. In lymphocytes, these properties are important for the formation of immunological memory, to generate cells with strong anti-tumor activity, and to generate highly pathogenic cells in situations of autoimmunity. We study how these processes are controlled by sequence-specific DNA-binding transcription factors, as well as their upstream regulators and downstream effectors. Transcription factors are by far the most dominant controllers of cell fate. They do this through their ability to bind to specific DNA sequences within chromatin and in conjunction with other DNA-bound factors. For this reason, transcription factors play central roles in development, cell fate decisions and cellular reprogramming. Aberrations in transcription factor function result in immune dysfunction, developmental defects, and cancer. Our research merges molecular biological and in vivo experiments to determine the function and physiological impact of transcription factor activity. One guiding principle is that, as enabling technologies allow for future drug development to focus on transcription factors and their cofactors, direct pharmaceutical targeting of gene expression will become increasingly prevalent

Some current major projects in the lab:

1. Interplay between transcription factors Oct1 and Oct4 in pluripotent cells and their differentiated progeny.
2. Spatiospecific Oct4 cofactors.
3. Oct4 redox regulation in reprogramming and peri-implantation development.
4. Topological interactions between linked T cell effector gene loci in naïve, activated, resting and restimulated T cells.
5. Roles of the transcriptional cofactor OCA-B/Pou2af1/Bob.1 in T cell memory, autoimmunity and anti-tumor immunity.
6. Exploiting OCA-B as a possible drug target.
7. Testing Oct1’s ability to improve human blood cell differentiation.

1. Effect of T-cell specific OCA-B knockout using a relapsing/remitting (NOD) model of multiple sclerosis. Mouse clinical disease scores were followed during initial presentation, 1^st remission and 1^st relapse, after which they become asynchronous. Differences were only significant upon relapse, where OCA-B knockout conferred strong protection.
2. Gene expression in key CNS T cell clusters based on single-cell RNA-seq of NOD.EAE mice at remission is shown.