RESEARCH ABSTRACT
Immune cells play a critical role in combating infections and cancers but can also be harmful in autoimmunity and immunopathologic states. Our laboratory combines efforts in both basic research and clinical investigation to advance the understanding of cancer immunology and to develop novel immunotherapies for cancer and autoimmune disorders.
Current projects in our laboratory are to understand how the modulation of immune cells receptor signals can be used to alter immune cell functions, and the interest of developing therapeutic strategies for immune cells mediated diseases.
Several projects are under investigation
- Investigating the impact of manipulating TCR signal transduction pathways in normal and disease models. More specifically, we are interested to study the role of adaptor molecule SLP-76 in hematological malignancies and bone marrow transplantation. We are also investigating the role of Tec family tyrosine kinases (ITK) that regulate lymphocyte development, activation, and differentiation. Itk is a Tec family tyrosine kinase that is activated upon TCR signaling and is required for full TCR-induced activation of PLC-γ, Ca2+ mobilization, and ERK activation. We are specifically investigating the role on ITK in cytokine production, T cells migration, and T cells effector function and chemokine receptor expression in both normal and disease models.
- T cells play critical roles in host defense against viruses, intra cellular microbe, and cancers. What is not clear is how the key transcription factors, T-box transcription factors, T-bet and Eomesodermin (Eomes) function as effector molecule in T cells during infection and immunopathologic states. We are also examining the role of the Wnt signal pathway, and T cell factor-1 (TCF1) signaling pathway, which is necessary for Eomes expression in naïve and memory CD8+ T cells during immunopathologic states.
- We are examining the role of NKG2D signaling and surface expression in graph verses tumor (GVT) response after allogeneic bone marrow transplantation. More specifically we are investigating the association between NKG2D expression and GVT responses, both clinically and in vitro in a cohort of HSCT recipients with acute myeloid leukemia (AML).
Rotation Projects are available in all areas
Lab personnel:
Principle Investigator Mobin Karimi
Selected manuscripts
- Mammadli, M., R. Harris, S. Mahmudlu, A. Verma, A. May, R. Dhawan, A. T. Waickman, J. M. Sen, A. August, and M. Karimi. "Human Wnt/Beta-Catenin Regulates Alloimmune Signaling During Allogeneic Transplantation." Cancers (Basel) 13, no. 15 (Jul 28 2021). https://dx.doi.org/10.3390/cancers13153798.
- Mammadli, M., R. Harris, L. Suo, A. May, T. Gentile, A. T. Waickman, A. Bah, A. August, E. Nurmemmedov, and M. Karimi. "Interleukin-2-Inducible T-Cell Kinase (Itk) Signaling Regulates Potent Noncanonical Regulatory T Cells." Clin Transl Med 11, no. 12 (Dec 2021): e625. https://dx.doi.org/10.1002/ctm2.625.
- Mammadli, M., W. Huang, R. Harris, A. Sultana, Y. Cheng, W. Tong, J. Pu, T. Gentile, S. Dsouza, Q. Yang, A. Bah, A. August, and M. Karimi. "Targeting Interleukin-2-Inducible T-Cell Kinase (Itk) Differentiates Gvl and Gvhd in Allo-Hsct." Front Immunol 11 (2020): 593863. https://dx.doi.org/10.3389/fimmu.2020.593863.
- Mammadli, Mahinbanu, Weishan Huang, Rebecca Harris, Hui Xiong, Samuel Weeks, Adriana May, Teresa Gentile, Jessica Henty-Ridilla, Adam T. Waickman, Avery August, Alaji Bah, and Mobin Karimi. "Targeting Slp76:Itk Interaction Separates Gvhd from Gvl in Allo-Hsct." iScience 24, no. 4 (2021/04/23/ 2021): 102286. https://www.frontiersin.org/articles/10.3389/fimmu.2020.593863/full.
- Weeks, S., R. Harris, and M. Karimi. "Targeting Itk Signaling for T Cell-Mediated Diseases." iScience 24, no. 8 (Aug 20 2021): 102842. https://dx.doi.org/10.1016/j.isci.2021.102842.
- Roy, N. H., M. Mammadli, J. K. Burkhardt, and M. Karimi. "Crkl Is Required for Donor T Cell Migration to Gvhd Target Organs." Oncotarget 11, no. 17 (Apr 28 2020): 1505-14. https://www.frontiersin.org/articles/10.3389/fimmu.2020.593863/full.
- Karimi, M. A., O. Aguilar, B. Zou, M. H. Bachmann, J. R. Carlyle, C. L. Baldwin, and T. Kambayashi. "A Truncated Human Nkg2d Splice Isoform Negatively Regulates Nkg2d-Mediated Function." J Immunol 193, no. 6 (Sep 15 2014): 2764-71. https://dx.doi.org/10.4049/jimmunol.1400920.
- Karimi, M. A., J. L. Bryson, L. P. Richman, A. D. Fesnak, T. M. Leichner, A. Satake, R. H. Vonderheide, D. H. Raulet, R. Reshef, and T. Kambayashi. "Nkg2d Expression by Cd8+ T Cells Contributes to Gvhd and Gvt Effects in a Murine Model of Allogeneic Hsct." Blood 125, no. 23 (Jun 4 2015): 3655-63. https://dx.doi.org/10.1182/blood-2015-02-629006.
- Karimi, M. A., E. Lee, M. H. Bachmann, A. M. Salicioni, E. M. Behrens, T. Kambayashi, and C. L. Baldwin. "Measuring Cytotoxicity by Bioluminescence Imaging Outperforms the Standard Chromium-51 Release Assay." PLoS One 9, no. 2 (2014): e89357. https://dx.doi.org/10.1371/journal.pone.0089357.
- Karimi, M., T. M. Cao, J. A. Baker, M. R. Verneris, L. Soares, and R. S. Negrin. "Silencing Human Nkg2d, Dap10, and Dap12 Reduces Cytotoxicity of Activated Cd8+ T Cells and Nk Cells." J Immunol 175, no. 12 (Dec 15 2005): 7819-28. https://dx.doi.org/10.4049/jimmunol.175.12.7819.
