Roland K. Strong
Ph.D., Harvard University, Biophysics, 1990.
B.S., University of Michigan, Biophysics, 1984.
Structural molecular immunology and vaccinology
We use the tools of structural molecular immunology (including biophysical methods such as x-ray crystallography, surface plasmon resonance interaction analysis (Biacore), small angle x-ray scattering, fluorescence and circular dichroism spectroscopy, and analytical ultracentrifugation) to study receptor/ligand interactions mediating immunity; current projects focus on: (1) immunorecognition of siderophores in infections and cancer, (2) AIDS vaccine development and (3) engineering novel immunotherapeutics.
(1) The mammalian protein Siderocalin (Scn, Lipocalin 2), found in neutrophil granules and secreted from a variety of cell types upon induction, specifically recognizes and binds to two families of ferric siderophores: catecholate siderophores, including those from enteric bacteria, and the soluble, mixed-type carboxymycobactins from mycobacteria. [Siderophores are small-molecule, ferric-specific chelators that facilitate microbial iron acquisition.] The best characterized function of Scn is to complement the general anti-bacterial iron-depletion strategy of the innate immune system by sequestering iron, as siderophore complexes, away from invading pathogens. We continue to search for Scn orthologs and strive to fully understand the complex relationship between Scn, bacterial siderophore variation and virulence. Scn has also been implicated in cellular processes unrelated to antibacterial activities, including apoptosis, differentiation and tumorigenesis. We are exploring possible mechanisms and receptor interactions that mediate these pleiotropic activities.
(2) An AIDS vaccine is desperately needed but, in general, the state-of-the-art in vaccine development has not yet achieved the ability to design vaccine immunogens that are capable of eliciting precisely targeted antibody specificities and functionalities, needed for an efficacious AIDS vaccine. We have pioneered the use of a new approach, ‘reverse vaccinology’ to design an AIDS vaccine, targeting several broadly-neutralizing antibody specificities (4E10, b12), but our efforts highlight the need to fully understand the evolution of antibodies during immune responses, including vaccination, and the precise molecular basis of neutralization. We are pursuing experiments to both understand how to make improved AIDS vaccine immunogens, by taking antibody evolution into account, and use our existing immunogens to better understand the process of antibody evolution. Novel approaches include using large-scale peptide arrays to assay autoreactivity and polyspecificity.
(3) Allogeneic hematopoietic cell transplantation (HCT) is an effective therapy for life-threatening, non-malignant disorders of the hematopoietic and immune systems. However, major limitations of allogeneic HCT in patients with nonmalignant disorders have been host-versus-graft reactions (graft rejection) and immune reactions of donor lymphocytes against host antigens, also called graft-versus-host disease (GVHD), both of which can be fatal. HCT recipients are generally treated with long term immunosuppressive regimens which weakens host immune responses to pathogens, thereby increasing the risk of serious infections – and is not uniformly successful in controlling GVHD. CD28 and CTLA-4 are leukocyte cell-surface costimulatory receptors that profoundly influence the course of immune responses: CD28 magnifies the effects of TCR signaling and enhances both cell cycle progression and T cell survival; CTLA-4 (CD152) provides opposing inhibitory signals. CD28 and CTLA-4 bind the shared, related ligands B7.1 (CD80) and B7.2 (CD86). The long-term goal of this project is to develop computationally-redesigned B7-based antagonists and agonists specific for CD28 or CTLA-4 for use as short-term immunotherapeutics in various clinical contexts, initially focusing on the control of host-versus-graft reactions and GVHD following allogeneic HCT. Other targets include therapeutically regulating iron metabolism in various disease contexts by reengineering Scn, related proteins and receptors and developing various antibodies as useful therapeutics or novel research tools.
American Association of Immunologists
NIH College of CSR Reviewers
Honors and Awards
2003, Morley Science Medal, Western Reserve Academy
1992-1994, Postdoctoral Fellowship, American Cancer Society
1990-1994, Postdoctoral Fellow, California Institute of Technology