RESEARCH PROGRAMS AND AFFILIATIONS
- Immunoreceptor signaling during development, homeostasis, and effector function of T cells and NK cells.
- T lymphocytes for adoptive cell therapy against hematological cancer.
- The role of the transcriptional regulator in alternative signal pathways to assess’ T cells cytotoxic function of hematological cancer cells
- The role of adaptor molecule SLP-76 in hematological malignancies and bone marrow transplantation
- The role of Tec family tyrosine kinases (ITK) and the activation of PLC-γ, Ca2+ mobilization, and ERK activation
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
1. 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, Ca 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.
2. 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.
3. 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
Principle Investigator Mobin Karimi
1. Karimi MA, Bryson JL, Richman LP, Fesnak AD, Leichner TM, Satake A, Vonderheide RH, Raulet DH, Reshef R, Kambayashi T. 2015. NKG2D expression by CD8+ T cells contributes to GVHD and GVT effects in a murine model of allogeneic HSCT. Blood 125: 3655-63
2. Huang Y, Clarke F, Karimi M, Roy NH, Williamson EK, Okumura M, Mochizuki K, Chen EJ, Park TJ, Debes GF, Zhang Y, Curran T, Kambayashi T, Burkhardt JK. 2015. CRK proteins selectively regulate T cell migration into inflamed tissues. J Clin Invest 125: 1019-32
3. Karimi MA, Aguilar OA, Zou B, Bachmann MH, Carlyle JR, Baldwin CL, Kambayashi T. 2014. A truncated human NKG2D splice isoform negatively regulates NKG2D-mediated function. J Immunol 193: 2764-71
4. Karimi MA, Lee E, Bachmann MH, Salicioni AM, Behrens EM, Kambayashi T, Baldwin CL. 2014. Measuring cytotoxicity by bioluminescence imaging outperforms the standard chromium-51 release assay. PLoS One 9: e89357
5. Abrahamsson AE, Geron I, Gotlib J, Dao KH, Barroga CF, Newton IG, Giles FJ, Durocher J, Creusot RS, Karimi M, Jones C, Zehnder JL, Keating A, Negrin RS, Weissman IL, Jamieson CH. 2009. Glycogen synthase kinase 3beta missplicing contributes to leukemia stem cell generation. Proc Natl Acad Sci U S A 106: 3925-9
6. Nishimura R, Baker J, Beilhack A, Zeiser R, Olson JA, Sega EI, Karimi M, Negrin RS. 2008. In vivo trafficking and survival of cytokine-induced killer cells resulting in minimal GVHD with retention of antitumor activity. Blood 112: 2563-74
7. E. M. Anderson, , , , , , , . Bispecific Antibody-Redirected Immunotherapy of Her2/neu-expressing Uterine Cancer. jim.bmj.com/content/54/1/S104.1
8. Peter C, Kielstein JT, Clarke-Katzenberg R, Adams MC, Pitsiouni M, Kambham N, Karimi MA, Kengatharan KM, Cooke JP. 2007. A novel bioluminescent tumor model of human renal cancer cell lines: an in vitro and in vivo characterization. J Urol 177: 2342-6
9. Duda J, Karimi M, Negrin RS, Contag CH. 2007. Methods for imaging cell fates in hematopoiesis. Methods Mol Med 134: 17-34
10. Chan JK, Hamilton CA, Cheung MK, Karimi M, Baker J, Gall JM, Schulz S, Thorne SH, Teng NN, Contag CH, Lum LG, Negrin RS. 2006. Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: a preclinical study. Clin Cancer Res 12: 1859-67
11. Verneris MR, Arshi A, Edinger M, Kornacker M, Natkunam Y, Karimi M, Cao YA, Marina N, Contag CH, Negrin RS. 2005. Low levels of Her2/neu expressed by Ewing's family tumor cell lines can redirect cytokine-induced killer cells. Clin Cancer Res 11: 4561-70
12. Karimi M, Cao TM, Baker JA, Verneris MR, Soares L, Negrin RS. 2005. Silencing human NKG2D, DAP10, and DAP12 reduces cytotoxicity of activated CD8+ T cells and NK cells. J Immunol 175: 7819-28
13. Verneris MR, Karimi M, Baker J, Jayaswal A, Negrin RS. 2004. Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cells. Blood 103: 3065-72
14. McCaffrey AP, Meuse L, Karimi M, Contag CH, Kay MA. 2003. A potent and specific morpholino antisense inhibitor of hepatitis C translation in mice. Hepatology 38: 503-8