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Dean Tantin Lab

    Welcome to the Tantin Laboratory!

    Our research emphasis is the regulation of gene expression, and the control of immune responses and stem cells by gene expression regulators. To study this control, we use mouse genetic models and derived cells, as well as human cells, along with genomic, molecular biological and biochemical approaches. A unifying theme is sequence-specific DNA binding transcription factors, especially members of the Oct/POU transcription factor family and their cofactors. Sequence-specific DNA binding transcription factors are the most potent controllers of gene expression, as demonstrated by their central role in development, cell fate decisions and reprogramming. Because the patterns of specific gene expression established by transcription factors are critical for successful development and signal response, aberrations in transcription factor function lead to myriad human disorders such as immune dysfunction, developmental defects and cancer. Our lab studies mammalian transcription factors, their upstream regulatory signals and downstream cofactors and mechanisms, to answer fundamental questions regarding lymphocyte development and function, stem cells, pluripotency and malignancy.

    Some current major projects in the lab:
    Roles of the transcriptional cofactor OCA-B/Pou2af1/Bob.1 in T cell memory, autoimmunity and anti-tumor immunity
    Exploiting the transcription coregulator OCA-B as a drug target
    Oct1/4 interplay in pluripotent cells and their differentiated progeny
    Redox regulation of Oct4 and implications in reprogramming and peri-implantation development

     

    Dean Tantin

    Professor
    Department of Pathology
    University of Utah School of Medicine

    Contact Us

    Huntsman Cancer Institute
    2000 Circle of Hope, Research South
    Room 3707 (LL376 for courier service)
    Salt Lake City, UT 84112-5550

    Lab Phone: 801-587-3802
    Office Phone: 801-587-3035
    Email: dean.tantin@path.utah.edu

    Lab administrative contact:
    Email: Alene.Schwei@hci.utah.edu
    Phone: 801-213-8428

    Lab manager:
    Email: zuolian.shen@path.utah.edu
    Phone: 801-587-3802

    Research

    -Molecular basis of the malignant, stem cell and memory lymphocyte phenotypes

    -Mechanisms of gene regulation by Oct transcription factors

    The major long-term goal of our research is to understand the transcriptional underpinnings of immune responses, stem cell function and the malignant state. Sequence-specific DNA binding transcription factors sculpt gene expression patterns by interacting with particular DNA sequences in our genomes. We use biochemical, genetic and genomic approaches to determine mechanisms and functions of these factors.

    Control of developmentally inducible gene expression in differentiating embryonic stem cells

    The embryonic stem cell master transcription regulator Oct4 is a potent controller of pluripotency. We identified a transcriptional mechanism hat Oct4 uses uniquely at its core pluripotency targets. This mechanism involves the Jmjd1c histone demethylase and FACT histone chaperone. Another category of Oct4 targets are developmental-specific genes that are silent but held in a configuration that allows them to be readily activated, or stably repressed, later in development. We are studying the role of Oct4 paralogs (e.g., Oct1) in this process. These proteins have similar in vitro DNA binding specificity as Oct4 and recognize many of the same target genes. We have found that pluripotent cells with inducible Oct1 knockout behave normally until differentiation, where they fail to induce developmentally appropriate genes, and aberrantly express developmentally inappropriate genes. Upon ESCs differentiation, Oct1 occupies Oct4 target genes, sometimes transiently. These results support a “handoff mode”, whereby activities related to Oct4 take over gene poising and gene silencing duties from Oct4 as cells differentiate and Oct4 is lost. We are determining whether this occurs genome-wide, and identifying the cofactors used in this process.

    Upstream control of Oct1 protein stability and cellular metabolism by BRCA1

    Oct1is widely expressed, but more highly expressed in somatic and cancer stem cell compartments, where it promotes glycolytic metabolic phenotypes. Interestingly mRNA levels remain unchanged. We have found that Oct1 protein is destabilized by BRCA1/BARD1 via its N-terminal E3 ligase activity. Consistently, we have found that BRCA1 promotes oxidative metabolic profiles. In primary breast cancer specimens, Oct1 protein levels tend to increase with tumor grade while BRCA1 declines. We are studying the biochemical and metabolic circuitry of this process, the effect of BRCA1 mutants and variants in Oct1 stability, and whether Oct1 promotes breast cancer tumorigenicity through metabolic mechanisms.

    Gene regulatory basis of CD4 T cell memory

    Oct1 controls target gene expression through related mechanisms that enforce either a repressed transcription state, or a silent but "poised" state. Poised gene expression states are indicative not only of stem cells, but also of memory lymphocytes. Interestingly, Oct1 controls CD4 T memory lymphocyte formation and activity. Oct1 is widely expressed but one of its cofactors, OCA-B, is induced in CD4 T cells upon activation. We found that T cell-specific OCA-B loss confers the same phenotype. We are studying whether OCA-B expression can be used to prospectively identify CD4 memory cells during ongoing immune responses, the ability of membrane-soluble peptide inhibitors to block this process, the role of these activities in CD8 T cells, and the ability of these proteins to coordinately regulate distant target genes by spatially localizing them together.

    Contribution of Oct1 to tissue regeneration and malignancy

    Oct protein is elevated in multiple tumor types. It promotes oncogenic transformation and its loss protects mice in several tumor models. In normal cells Oct1 is a somatic and cancer stem cell determinant. It promotes these functions through multiple pathways including control of cellular metabolism. We have found that Oct1 is dispensable for reconstitution of the blood system by hematopoietic stem cells, but is required in the case of serial or competitive transplants. In the gut, we have found that Oct1 is dispensable for normal homeostasis but required for regeneration. We are working to understand the molecular basis of these phenomena, and determining the role of Oct1 and cofactors in mouse models of leukemia and colon cancer.

    Select Publications

    • Baessler A, Novis CL, Shen Z, Perovanovic J, Wadsworth M, Thiede KA, Sircy LM, Harrison-Chau M, Nguyen NX, Varley KE, Tantin D, Hale JS. (2022) Tet2 coordinates with Foxo1 and Runx1 to balance T follicular helper cell and T helper 1 cell differentiation. Sci Adv. (in press) PMID: 35704571
    • Lin Y, Perovanovic J, Kong Y, Igyarto BZ, Zurawski S, Tantin D, Zurawski G, Bettini M, Bettini ML. (2022) Antibody-Mediated Targeting of a Hybrid-Insulin-Peptide Towards Neonatal Thymic Langerin+ Cells Enhances T Cell Central Tolerance and Delays Autoimmune Diabetes. Diabetes (in press) PMID: 35622068
    • Sun W, Guo J, McClellan D, Poeschla A, Bareyan D, Casey MJ, Cairns BR, Tantin D*, Engel ME* (2022). GFI1 Cooperates with IKZF1/IKAROS to Activate Gene Expression in T Cell Acute Lymphoblastic Leukemia. Mol Cancer Res 20:501. PMID: 34980595 *co-corresponding authors
    • Sun W, Jia X, Liesa M, Tantin D*, Ward DM* (2022). ABCB10 Loss Reduces CD4+ T Cell Activation and Memory Formation. J Immunol 208:328. PMID: 34893527 *co-corresponding authors
    • Kim H, Perovanovic J, Shakya A, Shen Z, German CN, Ibarra A, Jafek JL, Lin NP, Evavold BD, Chou DH, Jensen PE, He X, Tantin D (2021). Targeting transcriptional coregulator OCA-B/Pou2af1 blocks activated autoreactive T cells in the pancreas and type 1 diabetes. J Exp Med 218:e20200533. PMID: 33295943
    • Bensard CL, Wisidagama DR, Olson KA, Berg JA, Krah NM, Schell JC, Nowinski SM, Fogarty S, Bott AJ, Wei P, Dove KK, Tanner JM, Panic V, Cluntun A, Lettlova S, Earl CS, Namnath DF, Vzquez-Arregun K, Villanueva CJ, Tantin D, Murtaugh LC, Evason KJ, Ducker GS, Thummel CS, Rutter J (2020). Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier. Cell Metab 31:284. PMID: 31813825
    • McDonough JE, Ahangari F, Li Q, Jain S, Verleden SE, Herazo-Maya J, Vukmirovic M, DeIuliis G, Tzouvelekis A, Tanabe N, Chu F, Yan X, Verschakelen J, Homer RJ, Manatakis DV, Zhang J, Ding J, Maes K, De Sadeleer L, Vos R, Neyrinck A, Benos PV, Bar-Joseph Z, Tantin D, Hogg JC, Vanaudenaerde BM, Wuyts WA, Kaminski N (2019). Transcriptional regulatory model of fibrosis progression in the human lung. JCI Insight 4:e131597. PMID: 31600171
    • Jafek JL, Shakya A, Tai PY, Ibarra A, Kim H, Maddox J, Chumley J, Spangrude GJ, Miles RR, Kelley TW, Tantin D (2019). Transcription factor Oct1 protects against hematopoietic stress and promotes acute myeloid leukemia. Exp Hematol 76:38. PMID: 31295506
    • Kim H, Dickey L, Stone C, Jafek JL, Lane TE, Tantin D (2019). T cell-selective deletion of Oct1 protects animals from autoimmune neuroinflammation while maintaining neurotropic pathogen response. J Neuroinflamm 16:133. PMID: 31266507
    • Vzquez-Arregun K, Bensard C, Schell JC, Swanson E, Chen X, Rutter J, Tantin D (2019). Oct1/Pou2f1 is selectively required for colon regeneration and regulates colon malignancy. PLoS Genet 15:e1007687. PMID: 31059499
    • Shen Z, Formosa T, Tantin D (2018). FACT Inhibition Blocks Induction But Not Maintenance of Pluripotency. Stem Cells Dev 27:1693. PMID: 30319048
    • Vazquez-Arreguin K, Maddox J, Kang J, Park D, Cano RR, Factor RE, Ludwig T, Tantin D (2018). BRCA1 through Its E3 Ligase Activity Regulates the Transcription Factor Oct1 and Carbohydrate Metabolism. Mol Cancer Res 16:439. PMID: 29330289
    • Shen Z, Kang J, Shakya A, Tabaka M, Jarboe EA, Regev A, Tantin D (2017). Enforcement of developmental lineage specificity by transcription factor Oct1. Elife 6:e20937. PMID: 28537559
    • Kikani CK, Wu X, Paul L, Sabic H, Shen Z, Shakya A, Keefe A, Villanueva C, Kardon G, Graves B, Tantin D, Rutter J (2016). Pask integrates hormonal signaling with histone modification via Wdr5 phosphorylation to drive myogenesis. Elife 5:e17985. PMID: 27661449
    • Vazquez-Arreguin K, Tantin D (2016). The Oct1 transcription factor and epithelial malignancies: Old protein learns new tricks. Biochim Biophys Acta 1859:792. PMID: 26877236
    • Shakya A, Goren A, Shalek A, German CN, Snook J, Kuchroo VK, Yosef N, Chan RC, Regev A, Williams MA, Tantin D (2015). Oct1 and OCA-B are selectively required for CD4 memory T cell function. J Exp Med 212:2115. PMID: 26481684
    • Shakya A, Callister C, Goren A, Yosef N, Garg N, Khoddami V, Nix D, Regev A, Tantin D (2015). Pluripotency transcription factor Oct4 mediates stepwise nucleosome demethylation and depletion. Mol Cell Biol 35:1014. PMID: 25582194
    • Tantin D (2013). Oct transcription factors in development and stem cells: insights and mechanisms. Development 140:2857. PMID: 23821033
    • Kang J, Shen Z, Lim JM, Handa H, Wells L, Tantin D (2013). Regulation of Oct1/Pou2f1 transcription activity by O-GlcNAcylation. FASEB J 27:2807. PMID: 23580612
    • Yosef N, Shalek AK, Gaublomme JT, Jin H, Lee Y, Awasthi A, Wu C, Karwacz K, Xiao S, Jorgolli M, Gennert D, Satija R, Shakya A, Lu DY, Trombetta JJ, Pillai MR, Ratcliffe PJ, Coleman ML, Bix M, Tantin D, Park H, Kuchroo VK, Regev A (2013). Dynamic regulatory network controlling TH17 cell differentiation. Nature 496:461. PMID: 2347089
    • Manning J, Mitchell B, Appadurai DA, Shakya A, Pierce LJ, Wang H, Nganga V, Swanson PC, May JM, Tantin D, Spangrude GJ (2013). Vitamin C promotes maturation of T-cells. Antioxid Redox Signal 19:2054. PMID: 23249337
    • Maddox, J, Tantin, D (2013). Oct4, Oct1 and Cancer Stem Cells. In Cancer Stem Cells. Hoboken, NJ, U.S.A.: Wiley & Sons.
    • Maddox J, Shakya A, South S, Shelton D, Andersen JN, Chidester S, Kang J, Gligorich KM, Jones DA, Spangrude GJ, Welm BE, Tantin D (2012). Transcription factor Oct1 is a somatic and cancer stem cell determinant. PLoS Genet 8:e1003048. PMID: 23144633
    • Li Q, Shakya A, Guo X, Zhang H, Tantin D, Jensen PE, Chen X (2012). Constitutive nuclear localization of NFAT in Foxp3+ regulatory T cells independent of calcineurin activity. J Immunol 188:4268. PMID: 22490438
    • Ferraris L, Stewart AP, Kang J, DeSimone AM, Gemberling M, Tantin D, Fairbrother WG (2011). Combinatorial binding of transcription factors in the pluripotency control regions of the genome. Genome Res 21:1055. PMID: 21527551
    • Shakya A, Kang J, Chumley J, Williams MA, Tantin D (2011). Oct1 is a switchable, bipotential stabilizer of repressed and inducible transcriptional states. J Biol Chem 286:450. PMID: 21051540
    • Kiesler P, Shakya A, Tantin D, Vercelli D (2009). An allergy-associated polymorphism in a novel regulatory element enhances IL13 expression. Hum Mol Genet 18:4513. PMID: 19706623
    • Kang J, Shakya A, Tantin D (2009). Stem cells, stress, metabolism and cancer: a drama in two Octs. Trends Biochem Sci 34:491. PMID: 19733480
    • Shakya A, Cooksey R, Cox JE, Wang V, McClain DA, Tantin D (2009). Oct1 loss of function induces a coordinate metabolic shift that opposes tumorigenicity. Nat Cell Biol 11:320. PMID: 19219035
    • Kang J, Gemberling M, Nakamura M, Whitby FG, Handa H, Fairbrother WG, Tantin D (2009). A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress. Genes Dev 23:208. PMID: 19171782

    Lab Members

    Dean Tantin, PhD

    Dean Tantin is a Professor in the Department of Pathology at the University of Utah and a member of the Nuclear Control of Cell Growth and Differentiation Program at Huntsman Cancer Institute.    Tantin studies the regulation of gene expression and its relationship to immune and stem cell function, and malignancy. He focuses on a class ... Read More

    Research Interests: Development and Regulation of Immune Responses, Gene Regulation, Stem Cells, Transcriptional Control of Malignant State

    Phone: 801-587-3035

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    Zuolian Shen, PhD

    Postdoctoral Fellow

    Zuolian graduated from China Agricultural University. She is working on the Oct1 regulation in embryonic stem cell development and differentiation and Oct4 roles in induced pluripotent stem cells.

    Email

    Erik Hughes, BS

    Graduate Student

    Erik Hughes graduated from Westminster College with a BS in Biological Sciences. After his undergraduate, he worked in the life science industry for several years developing iPSC based tools and technologies. Erik joined the Molecular Biology Ph.D. program in 2018. In 2019, Erik joined the Tantin Lab where he is researching the transcriptional cofactor OCA-B and its impact on autoimmune diseases such as multiple sclerosis and type 1 diabetes. He is grateful for the opportunity to work with all the amazing researchers here at the University of Utah.

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    Yifan Wu, MS

    Graduate Student

    Yifan obtained her undergraduate degree from South China University of Technology and the University of Edinburgh, and her master’s degree from the University of Southern California. She joined the Molecular Biology Ph.D. program in 2019 and joined the Tantin Lab in the next year. She currently focuses on the role of Oct1 in embryonic stem cell development and Oct1-mediated interchromosomal interactions in immune cells. She is very excited about the ongoing research and looking forward to making more progress in the Ph.D. at the University of Utah.

    Email

    Asit Manna, PhD

    Postdoctoral Fellow

    I obtained my PhD in Biochemistry from the University of Calcutta, India. Then I moved to NIH for my postdoctoral research, where I worked on a signal transducing protein known as LAT. More specifically, I studied the ability of LAT to act as a multi-protein complex involved in T cell activation using chemical biology, biophysics and structural biology tools. In Dr. Tantin’s lab, I am working on OCT4 and OCT1 protein interactions with their partners involved in transcriptional regulation.

    Email

    Junhong Du, MS

    Graduate Student

    Junhong graduated from South China Normal University with a bachelor’s degree in Biotechnology. He conducted Cancer Biology research at the University of Pennsylvania and obtained a master’s degree in Biotechnology. He joined the Molecular Biology Ph.D. program in 2021 and the Tantin Lab in 2022. In the lab, his research focuses on tumor immunity and autoimmunity. He enjoys working in the lab and wants to make progress in cancer immunotherapy.

    Email

    Tantin Lab Alumni

    Jelena Perovanovic, PhD

    Scientist II, Computational Biology
    Recursion Pharmaceuticals

    Wenxiang Sun, PhD

     

    Research Scientist
    Sumitomo Biosciences

    Catherine Callister, MD

    Medical Resident, Geriatrics
    Johns Hopkins University School of Medicine

    Reuben Ryan Cano

     

    MD/PhD Candidate
    MSTP program
    Duke University
    Durham, NC

    Cody N. German, MS

    Pathology Technician
    Intermountain Healthcare Central Laboratory

    Jenny Hong-Gonzalez

    Associate Director, Intellectual Property
    CytomX Therapeutics, Inc.
    151 Oyster Point Blvd. #400
    South San Francisco, CA 94080

    Jinsuk Kang, PhD

     

    Principal Research Scientist
    Discovery Research I
    C&C Research Laboratories

    Heejoo Kim, PhD

     

    Postdoctoral Fellow
    Johnson & Johnson Research and Development
    San Diego, CA

    Jessica Maddox, MD/PhD

    Pediatrics Specialist
    Saint Alphonsus Hospital
    Boise, ID

    Arvind Shakya, PhD/DVM

    Senior Scientist, Pharmacology
    Cellgene, Inc
    San Diego, CA

    Samuel South, MD

     

    Fellow, General Surgery Specialist
    University of Utah School of Medicine

    Karina Vázquez-Arreguín, PhD

    Postdoctoral Fellow
    Balveen Kaur laboratory
    Department of Neurosurgery
    UTHealth
    Houston, TX

    Protocols

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    Q&A

    2020:
    Where are you from?
    TANTIN: California’s own beautiful San Fernando Valley

    Why did you decide to focus on research?
    TANTIN: https://www.the-scientist.com/news-opinion/opinion-star-trek-medicine-36460

    What is your approach to embarking on new research projects?
    TANTIN: This is a complex calculation. It has to do with interest in the subject, capacity to carry out experiments in a reasonable time, where we are relative to the rest of the biomedical community, monetary resources and future grant funding. Because of competition built in to the NIH grant funding system, our ability to conduct research is contingent on 4-5 year renewal cycles. So we have to keep these incremental timeframes in mind when embarking on something new and long-term.

    What is your approach to mentoring?
    TANTIN: I set up regular weekly meetings with trainees and go to find them when I’m curious about something. For people coming to me, I have an open-door policy. If I’m here anyone can drop by at any time. This is especially important with newer trainees who should feel they can talk to me any time.

    2018:
    Talk about Salt Lake City and Utah. What do you and lab members do for fun?
    TANTIN: Salt Lake is a big reason I came here. If you like the outdoors as I do, it’s a real paradise. I visited a couple National Parks a year since arriving. Some of Utah’s State Parks and BLM land would certainly qualify as National Parks if they were located elsewhere. It’s just our abundance of riches. In addition, destinations in Wyoming, Idaho, Nevada, Colorado, Montana and California are within a day’s drive. Skiing, hiking and other outdoor sports are everywhere. There is also a robust cultural scene.

    How does your lab fit within the greater University?
    TANTIN: It’s an outstanding place to do science. In particular with our lab, we have our fingers in a lot of different pots. We participate in efforts with the Department of Pathology and Division of Microbiology&Immunology, the Huntsman Cancer Institute as well as the Immunology, Inflammation & Infectious Disease Initiative here, among others. We are physically situated within the cancer center. We collaborate with people spanning the entire Health Sciences Center, which comprises hundreds of labs with every conceivable type of expertise. It’s also a world-class center of clinical expertise, allowing us to conduct translational studies. It’s a scientist’s playground.

    Can you summarize what your lab does in three words or less?
    TANTIN: “Applied gene regulation”

     

    2014:
    What does your lab study?
    TANTIN:
     The unifying theme is gene regulation by sequence-specific DNA binding transcription factors. We seek to understand how transcription factors receive signals, how they regulate their downstream targets, and the biological consequences. Because some of the transcription factors we are studying are multifaceted, we wind up studying an array of different biological systems and disease states, for example lymphocyte development and function, early embryonic development, stem cells, and cancer - both solid and hematological tumors.

    Would you classify your lab research as basic or translational?
    TANTIN: I would classify it as basic research. Even if an activity we are studying controls a disease state, for example the transcription factor Oct1 and the maintenance of a leukemia phenotype, our goal is to understand the basic molecular mechanisms that underlie control of that phenotype. As our research progresses and these projects reach a threshold of understanding, we start thinking about application and clinical translation. For example, we now know that Oct1 is overexpressed at the protein level (but not message level) in several forms of “cancer stem cells”. That information raises the question of whether or not Oct1 could be used as a prognostic marker in certain forms of malignancy.

    Why is basic research still important and why do you conduct basic research?
    TANTIN: This is an important question. As I said above, we only start thinking about translation when our basic projects have reached a certain advanced stage of maturity. Not doing so would result in a train wreck. Translation is inefficient enough. Conducting it without basic understanding makes the odds of return on that investment unfavorable. You can think of it like a pyramid with basic research as the base. You would never invest most of the resources in building the top of the pyramid without supporting the base. Doing so would result in an “upside-down pyramid” and any 4 year-old can tell you what happens to a structure like that. Now as far as your second question goes, I just enjoy the discovery component, by which I mean finding out how things work at a basic molecular level.

    When did you first start your present line of experimentation?
    TANTIN: That is a hard one to pin down. I began work on the family of transcription factors we still study in 1998, as a postdoc in Phil Sharp’s lab at MIT. Since then I have studied different members, but the focus on that transcription factor family is still there. In 2004 I discovered that loss of one the factors I mentioned before, Oct1, did not have the effects we were expecting. Cells grew normally, they looked normal in a light microscope, but they were sensitive to different forms of stress like ionizing radiation for example. I like to highlight that date as a point of departure, as well as 2009, when my lab showed that Oct1 did not really activate target genes very well, but instead was very good at insulating them from repression. Subsequently in 2011 we identified the mechanism. A lot of our current efforts are devoted to understanding the biological implications and whether other members of this family use similar mechanisms.