Yuri Sykulev, MD, PhD
Associate Professor
Microbiology and Immunology

Contact Dr. Sykulev

233 S. 10th Street
Room 706
Philadelphia, PA 19107

(215) 503-4530

Education
Education

University Appointment
Associate Professor
Microbiology and Immunology
Thomas Jefferson University

Research and Clinical Interests
The major goal of my research program is to understand molecular mechanisms of T cell activation. I am building the program along two principal directions. The first direction is to investigate the biochemistry of T cell receptors and other immune receptors involved in antigen recognition by T cells. Having established Drosophila-based expression system to produce soluble analogs of these molecules, we systematically investigate affinity, kinetics and thermodynamics of the reactions involving these receptors. In parallel, we also study behavior of these molecules as they appear at the surface of live cells using modern visualization techniques, such as confocal microscopy and 3D microscopy. Any information derived form these experiments promises to shed light on what is now thought to be a hallmark of T cell activation, namely, formation of molecular assemblies located in distinct membrane compartments induced by productive engagement of T cell receptors with an antigen. Various recruitment patterns of the immune receptors to the membrane activating domains are thought to trigger distinct T cell responses and, thus, provide an explanation for essential flexibility in T cell responsiveness, the most intriguing feature of T cell behavior and functions.
The second direction aims to contribute to the development of new strategies of T cell vaccination. The significance of these efforts is emphasized by widely accepted believe that the induction of an effective T cell response is necessary and essential for successful host defense against viral or bacterial infection. While many new vaccination strategies are now becoming available, there are no suitable criteria to evaluate the efficacy of T cells raised in response to vaccination. Meanwhile, these criteria would help to distinguish between more or less promising vaccines during clinical trials. Speaking succinctly, it is essential to make a distinction between "good" and "bad" T cells. Quantitative analysis of molecular interactions between the immune receptors that we are studying will be useful for establishment of such criteria.
Both directions complement each other and should have both fundamental and practical implications. This research program is supported by a research grant from NIH (RO1) and W.W. Smith Charitable Trust Award.

Publications

1. Mechanisms controlling granule-mediated cytolytic activity of cytotoxic T lymphocytes
2. Quantum dots as a unique nanoscaffold to mimic membrane receptor clustering
3. Mechanisms controlling granule-mediated cytolytic activity of cytotoxic T lymphocytes
4. T cell receptor signaling kinetics takes the stage
5. Changing separating distances between immune receptors as a sensitive mechanism regulating T-cell activation
6. A novel composite immunotoxin that suppresses rabies virus production by the infected cells
7. A novel composite immunotoxin that suppresses rabies virus production by the infected cells
8. Kinetics of Early T Cell Receptor Signaling Regulate the Pathway of Lytic Granule Delivery to the Secretory Domain
9. Can oligomeric T-cell receptor be used as a tool to detect viral peptide epitopes on infected cells?
10. How a T cell receptor-like antibody recognizes major histocompatibility complex-bound peptide
11. Protein kinase C theta regulates stability of the peripheral adhesion ring junction and contributes to the sensitivity of target cell lysis by CTL.
12. Tpl2 and ERK transduce antiproliferative T cell receptor signals and inhibit transformation of chronically stimulated T cells
13. Quantum dot/peptide-MHC biosensors reveal strong CD8-dependent cooperation between self and viral antigens that augment the T cell response
14. Structural basis for degenerate recognition of natural HIV peptide variants by cytotoxic lymphocytes
15. Antagonism of HIV-specific CD4+ T cells by C-terminal truncation of a minimum epitope
16. ICAM-1 co-stimulates target cells to facilitate antigen presentation
17. Distinct role of lymphocyte function-associated antigen-1 in mediating effective cytolytic activity by cytotoxic T lymphocytes
18. Major histocompatibility complex class I-intercellular adhesion molecule-1 association on the surface of target cells: Implications for antigen presentation to cytotoxic T lymphocytes
19. Antibody specific for the peptide·major histocompatibility complex: Is it T cell receptor-like?
20. Cytotoxic T lymphocytes form an antigen-independent ring junction

(This list reflects the most recent 20 publications)