Mahmood Bilal

The Role of Grb2 family members in T cell Receptor (TCR)-mediated signaling events

I am interested in understanding the molecular events initiated by TCR activation. Specifically, I am focused on understanding how the Grb2 family of adaptor proteins, mediate and control signaling complexes that are crucial for signal transduction downstream of the TCR. The project is centered on studying the mechanism by which Grb2 and Grap assemble SH3 domain ligands at the LAT signaling complex. To this end, I plan to examine these events using human peripheral blood T cells and T cell lines where the expression of Grb2 or Grap have been suppressed by microRNA interference. These studies will help define the role of Grb2 family members and SH3/SH2 domain ligands in signaling pathways associated with disease, including leukemia and lymphomas.

Bilal MY, Houtman JCD. Transmission of T Cell Receptor-Mediated Signaling via the GRB2 Family of Adaptor Proteins. In: Soboloff J, Kappes DJ, editors. Signaling Mechanisms Regulating T Cell Diversity and Function. Boca Raton (FL): CRC Press/Taylor & Francis; 2018. Chapter 9. PubMed PMID: 30427631.

Bilal MY, Vacaflores A, Houtman JC. Optimization of methods for the genetic modification of human T cells. Immunol Cell Biol. 2015 Nov;93(10):896-908. doi:10.1038/icb.2015.59. PubMed PMID: 26027856; PubMed Central PMCID: PMC4659746.

Bilal MY, Houtman JC. GRB2 Nucleates T Cell Receptor-Mediated LAT Clusters That Control PLC-γ1 Activation and Cytokine Production. Front Immunol. 2015 Mar 30;6:141. doi: 10.3389/fimmu.2015.00141. eCollection 2015. PubMed PMID: 25870599; PubMed Central PMCID: PMC4378308.

Bilal MY, Zhang EY, Dinkel B, Hardy D, Yankee TM, Houtman JC. GADS is required for TCR mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells. Cell Signal. 2015 Apr;27(4):841-50. doi:10.1016/j.cellsig.2015.01.012. Epub 2015 Jan 28. PubMed PMID: 25636200; PubMed Central PMCID: PMC4339522.

Chapman NM, Yoder AN, Barbón KM, Bilal MY, Connolly SF, Houtman JC. Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells. J Leukoc Biol. 2015 Feb;97(2):285-96. doi: 10.1189/jlb.2A1013-568RRR. Epub 2014 Nov 11. PubMed PMID: 25387834; PubMed Central PMCID: PMC4304419.

Tremblay MM, Bilal MY, Houtman JC. Prior TLR5 induction in human T cells results in a transient potentiation of subsequent TCR-induced cytokine production. Mol Immunol. 2014 Feb;57(2):161-70. doi:10.1016/j.molimm.2013.09.002. Epub 2013 Oct 12. PubMed PMID: 24128895; PubMed Central PMCID: PMC3845368.

Chapman NM, Bilal MY, Cruz-Orcutt N, Knudson C, Madinaveitia S, Light J, Houtman JC. Distinct signaling pathways regulate TLR2 co-stimulatory function in human T cells. Cell Signal. 2013 Mar;25(3):639-50. doi:10.1016/j.cellsig.2012.11.026. Epub 2012 Dec 5. PubMed PMID: 23219913; PubMed Central PMCID: PMC3883577. Med PMID: 24128895; PubMed Central PMCID: PMC3845368.

Honors and Awards

  • 2010 Autumn Immunology Conference – John H. Wallace Fellowship
  • Predoctoral Training Grant in Immunology (NIH 2 T32 AI007485-16)
Associate of Pathology
HLA Laboratory Director in Training
University of Iowa
Mahmood Bilal