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Dean Tantin

Assistant Professor of Pathology

B.S. University of California, San Diego

Ph.D. University of California, Los Angeles

Research

References

dean.tantin@path.utah.edu

Dean Tantin's Lab Page

Dean Tantin's PubMed Literature Search

Research

Our interests lie in the elucidation of mammalian transcription factor function and in understanding transcription factor circuitries. Transcription factors are used to achieve specific gene expression patterns. Because these patterns are critical for successful development and signal response, aberrations in transcription factor function frequently underlie human disorders such as cancer and immune dysfunction. Our laboratory employs biochemical, genetic and genomic approaches to determine transcription factor function in stem cells, in tumorigenesis, during lymphocyte development/function, and to elucidate specific gene regulatory circuits in normal and diseased cells. Our efforts focus on gene regulation both from the perspective of mechanisms of action and biological effects of specific transcription factors, as well as the means of coordinate and reciprocal regulation of important groups of genes.

We are investigating the properties of an unusual class of homeodomain-related transcription factors that includes the stem cell master regulator Oct4, and a group of paralogs expressed in an overlapping pattern in adult tissue. The prototypic member of this class is Oct1, which is widely expressed in adult cells. Oct2 expression is largely confined to B lymphocytes and the central nervous system. Oct1, Oct2 and Oct4 recognize the same sequences in vitro, but have overlapping and distinct targets in vivo.

We are most interested in four areas 1) how this proteins respond to signals, 2) how the regulate the expression of their targets, 3) the extent of cross-talk between them, and 4) the physiological implications. Regarding the first area, we have found that these proteins are signal integrators—coupling cellular metabolic, oxidative and genotoxic stress inputs to transcriptional output through protein phosporylation, glycosylation and ubiquitination at conserved sites. These signals result in dynamic changes in protein activity. How these multiple modifications are generated and their functions are an active area of investigation. Regarding the second area, we have found that these proteins use different mechanisms to regulate target gene expression depending on context and received signals. In many instances, Oct proteins block stable repression, rather than directly activate, their targets (gene poising). Regarding the third, we have identified heavy intercommunication between Oct1 and Oct4 in embryonic stem (ES) cells.

Physiologically, we have found that Oct1 is an upstream determinant of somatic and tumor stem cells. We have also identified significant defects in CD4 memory T cell formation in the absence of one of these proteins, Oct1. We are interested in determining whether common mechanisms underlie the memory and stem cell defects.

(A) Oct-1 deficiency inhibits the stem cell side population (boxed, +Dox vs. -Dox). (B) Oct1 deficiency impairs tumor initiating frequency (right vs left flank)

References