Ph.D.

Associate Professor

Bioengineering

Associate Professor of Surgery & Molecular Microbiology and Immunology

School of Medicine

About Me

Research Interests

• Structure/function of antigen receptors of the adaptive immune system
• Development of novel immunotherapies based on manipulation of antigen receptors

Areas of Expertise

• Cancer Biology
• Cell Biology
• Developmental Biology
• Gene Expression
• Immune Response to Pathogens
• Innate Immunity
• Inflammation
• Intracellular trafficking
• Molecular Evolution
• Signal transduction
• Structural Biology
• Biochemistry
• Immunology
• Bioengineering
• Network Biology

Research Profile

Diana Gil Pagés, PhD, investigates how antigen recognition by T cell receptors (TCRs) turns on cell adaptive immune function. Specifically, she is focused on the TCR-associated CD3 multiprotein complex, and is the principal discoverer of the CD3 conformational change (CD3∆c), which is at the foundation of her ongoing research. Dr. Gil Pagés is studying the various levels of control exercised over CD3∆c, including structural, biochemical, developmental and physiological aspects. Her work is grounded in technical innovation and data reproducibility, with an emphasis in biochemistry and primary immune cell function. She is building on the current understanding of CD3∆c to translate knowledge into in vivo therapies for metastatic cancers. Focus areas • Fragment antigen-binding (Fab) fragments. Dr. Gil Pagés pioneered a new “mono-Fab” approach that allows scientists to provide CD3∆c in trans, to complement and strengthen T cell signals in response to physiological antigens presented by tumors. This innovation is a direct step toward exogenous CD3∆c provision for therapeutic application in people. • T cell co-potentiation. Dr. Gil Pagés developed this novel concept, which is relevant to receptor signaling, pharmacoregulation and immunotherapy. It applies when an intrinsically inert compound displays a specific latent potency: It binds a receptor, producing no functional effect on the receptor or the cell bearing it, but enhancing signaling and cellular responses when certain, specific physiological ligands (but not others) also are engaged. In combination with other immunotherapy strategies, T cell co-potentiation may produce the best anti-metastatic tumor responses and extend the lives of cancer patients. Dr. Gil Pagés and colleagues are currently working to establish whether co-potentiation is possible for human T cells, with the hope of pursuing clinical trials to test its therapeutic value. Significance to patient care Dr. Gil Pagés’ long-term goal is to exploit the knowledge generated in the lab to develop novel strategies to manipulate T cell adaptive immune function for therapeutic purposes.

Credentials

Undergraduate

1995, BS, Universidad Autonoma de Madrid

Graduate

2002, PhD, Universidad Autonoma de Madrid

Fellowship

2007, University Hospital, Basel, Switzerland

Publications

1. Goplen NP, Saxena V, Knudson KM, Schrum AG, Gil D, Daniels MA, Zamoyska R, Teixeiro E. 2016.  IL-12 Signals through the TCR To Support CD8 Innate Immune Responses.  J Immunol. 2016 Sep 15; 197(6):2434-43. doi: 10.4049/jimmunol.1600037. Epub 2016 Aug 12.  PMID: 27521342
2. Smith SE, Neier SC, Reed BK, Davis TR, Sinnwell JP, Eckel-Passow JE, Sciallis GF, Wieland CN, Torgerson RR, Gil D, Neuhauser C, Schrum AG. 2016.  Multiplex matrix network analysis of protein complexes in the human TCR signalosome.  Sci Signal. 2016 Aug 2;9(439):rs7. doi: 10.1126/scisignal.aad7279.  PMID: 27485017
3. Smith SE, Maus RL, Davis TR, Sundberg JP, Gil D, Schrum AG. 2016.  Maternal IL-6 can cause T-cell-mediated juvenile alopecia by non-scarring follicular dystrophy in mice.  Exp Dermatol. 2016 Mar;25(3):223-8. doi: 10.1111/exd.12914. Epub 2016 Feb 10.  PMID: 2666033
4. Hoffmann MM, Molina-Mendiola C, Nelson AD, Parks CA, Reyes EE, Hansen MJ, Rajagopalan G, Pease LR, Schrum AG, Gil D. 2015.  Co-potentiation of antigen recognition: A mechanism to boost weak T cell responses and provide immunotherapy in vivo.  Sci Adv. 2015 Oct 2;1(9):e1500415. doi: 10.1126/sciadv.1500415. eCollection 2015 Oct.  PMID: 26601285
5. Reed BK, Chopp LB, Malo CS, Renner DN, Van Keulen VS, Girtman MA, Nevala WN, Pavelko KD, Gil D,Schrum AG, Johnson AJ, Pease LR. 2015.  A Versatile Simple Capture Assay for Assessing the Structural Integrity of MHC Multimer Reagents.  PLoS One. 2015 Sep 21;10(9):e0137984. doi: 10.1371/journal.pone.0137984. eCollection 2015.  PMID:  26389800
6. Reed BK, Lee KA, Bell MP, Gil D, Schrum AG.  2014.  Detection of constant domain of human T cell antigen receptor alpha-chain via novel monoclonal antibody 7F18.   Monoclon Antib Immunodiagn Immunother. 2014 Dec;33(6):386-92. doi: 10.1089/mab.2013.0086.  PMID:  25545207
7. Smith SE, Nei7er SC, Davis TR, Pittelkow MR, Gil D, Schrum AG. 2014.  Signalling protein complexes isolated from primary human skin-resident T cells can be analysed by Multiplex IP-FCM.   Exp Dermatol. 2014 Apr;23(4):272-3. doi: 10.1111/exd.12362.  PMID:  24588717