Before you can repair a car, you have to know what each part is, what it does and how it fits together with other parts to power the vehicle. The body’s immune system is a powerful vehicle for fighting disease, and it is comprised of many parts with intricate and specific functions that make the system run. But the system can easily go off course, leading to cancer or autoimmune disease where the body attacks itself.
The immune system is extremely complex and influenced by many factors, including genetics and the environment. Scientists are still trying to understand how each independent part works so they can unlock ways to repair the immune system when it malfunctions.
In my lab, we study how the immune system develops normally. In particular, we focus on T cells and how they function within the immune system. T cells are formed in the thymus and help protect the body against infection and disease. For the immune system to function properly, T cells must recognize you but not react against you or your tissues. So, the thymus serves as a sort of university where T cells learn how they should function in the body.
Using a mouse model, we modify the T cells and observe what molecules and proteins are important in the immune system’s function. By blocking the development of T cells or altering other factors associated with them, we can make changes in the way the cells respond to one another. From what we observe, we hope to learn how T cells control the immune response and develop new methods for dealing with disease.
During T-cell development, a pool of precursor immature thymocytes undergoes a complex process of differentiation that results in the generation of two main lineages of mature T cells; CD4 T cells, which act as the orchestrators of the adaptive immune response, and CD8 T cells, which are programmed to elicit cytotoxic functions. The correct undertaking of this process plays a central role in the homeostasis of the immune system and in its ability to successfully control infections while maintaining self-tolerance. I use a genetic approach to understand the molecular events that regulate these differentiation processes.
The mechanisms that regulate CD4/CD8 lineage commitment have been the object of intense study during the last decade. Two main models, stochastic and instructional, were proposed to explain how MHC specificity and co-receptor expression are linked during development. The instructional model proposes that recognition and co-engagement of TCR/CD8 by class I MHC or of TCR/CD4 by class II MHC will instruct the cells to follow a CD8 or a CD4 developmental pathway, respectively. IT has been proposed that the distinct instructional signal would be delivered through the co-receptor. My experiments indentified the tyrosine kinase, Lck, as the critical component in this process. Subsequent experiments in my laboratory showed that the transcription factor, GATA-3, is also a central component of the program that directs development of CD4 T cells in the thymus.
The main focus of my laboratory at the moment is to understand how GATA-3 controls this lineage decision. To that intent, we are trying to a) determine the signal transduction elements that regulate GATA-3 expression during CD4/CD8 lineage commitment, connecting it to the Lck signals at this state; b)analyze the mechanism of action of GATA-3 using structure-function analysis; c) identify GATA-3 targets during CD4 lineage differentiation in the thymus; and d) understand the interactions between GATA-3 and TH-POK, a zinc-finger transcription factor recently identified as a central player in the development of the CD4 lineage.
M.D., University of Valencia (Spain), 1987
Ph.D., University Central, Barcelona (Spain), 1992
Honors and Awards
1988 Medical Degree’s “Extraordinary Award”, University of Valencia
1991 Visiting research fellow (EMBO short term fellowship) at the Lymphocyte Activation Laboratory (Dr. D.A. Cantrell), Imperial Cancer Research Fund, January to April
1992 Ph. Degree’s “Extraordinary Award”, University of Barcelona
1996-1997 Leukemia Society of America Senior Fellow. University of Washington
1998-2002 Pew Scholar
2000-2004 Cancer Research Institute Special Fellow
Associate Editor, Immunologia, PLoS ONE
American Association of Immunologists
Sociedad Española De Immunologia
Joined OMRF Scientific Staff in 2005
Simmons A, Alberola-Ila J. Retroviral transduction of T cells and T cell precursors. Methods Mol Biol 1323:99-108, 2016. [Abstract]
Iida R, Welner RS, Zhao W, Alberola-Ila J, Medina KL, Zhao ZJ, Kincade PW. Stem and Progenitor Cell Subsets Are Affected by JAK2 Signaling and Can Be Monitored by Flow Cytometry. PLoS One 9:e93643, 2014. [Abstract]
Fenutria R, Martinez VG, Simoes I, Postigo J, Gil V, Martinez-Florensa M, Sintes J, Naves R, Cashman KS, Alberola-Ila J, Ramos-Casals M, Soldevila G, Raman C, Merino J, Merino R, Engel P, Lozano F. Transgenic Expression of Soluble Human CD5 Enhances Experimentally-Induced Autoimmune and Anti-Tumoral Immune Responses. PLoS One 9:e84895, 2014. [Abstract]
Hu T, Wang H, Simmons A, Bajaña S, Zhao Y, Kovats S, Sun XH, Alberola-Ila J. Increased level of E protein activity during invariant NKT development promotes differentiation of invariant NKT2 and invariant NKT17 subsets. J Immunol. 2013 Nov 15;191(10):5065-73. [Abstract]
Shimazu T, Iida R, Zhang Q, Welner RS, Medina KL, Alberola-Ila J, Kincade PW. CD86 is expressed on murine hematopoietic stem cells and denotes lymphopoietic potential. Blood. 2012 May 24;119(21):4889-97. [Abstract]
Hu T, Simmons A, Yuan J, Bender TP, Alberola-Ila J. The transcription factor c-Myb primes CD4(+)CD8(+) immature thymocytes for selection into the iNKT lineage. Nat Immunol 11:435-441, 2010. [Abstract]
Hu T, Gimferrer I, Simmons A, Wiest D, Alberola-Ila J. The Ras/MAPK pathway is required for generation of iNKT cells. PLoS One. 2011 May 10;6(5):e19890. [Abstract]
Gimferrer I, Hu T, Simmons A, Wang C, Souabni A, Busslinger M, Bender TP, Hernandez-Hoyos G, Alberola-Ila J. Regulation of GATA-3 expression during CD4 lineage differentiation. J Immunol. 2011 Apr 1;186(7):3892-8. [Abstract]
Hu T, Simmons A, Yuan J, Bender TP, Alberola-Ila J. The transcription factor c-Myb primes CD4+CD8+ immature thymocytes for selection into the iNKT lineage. Nat Immunol. 2010 May;11(5):435-41. [Abstract]
Immunobiology and Cancer Research Program, MS 17
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-2025
Fax: (405) 271-8237