Daniel Jane-Wit, MD/PhD, RPVI

Assistant Professor

Research Departments & Organizations

Internal Medicine: Cardiovascular Medicine

Human and Translational Immunology Program

Vascular Biology and Therapeutics Program

Research Interests

Endothelium, Vascular; Heart Transplantation; Transplantation Immunology

Research Summary

Using sera from transplant patients to study the effects of complement, a set of circulating pro-inflammatory immune proteins involved in transplant rejection, we have identified a novel complement-mediated effector pathway, non-canonical NF-kB in endothelial cells (EC). This pathway activated a broad range of inflammatory molecules in EC and potentiated the ability of EC to activate alloimmune CD4+ T cells. Non-canonical NF-kB activation was detected in cultured human EC, in human coronary artery xenografts implanted in immunodeficient mice, and in biopsy specimens from five different patient cohorts with systemic complement activation. As such, inhibition of this pathway may have clinical implications for a broad number of complement-mediated conditions including transplant rejection and connective tissue disorders like lupus and rheumatoid arthritis.

Using a genome-wide siRNA screen, we have found that non-canonical NF-kB activation by complement occurs entirely intracellularly on Rab5+ vesicles which, following complement treatment, become a signaling platform that recruits signaling components that are entirely distinct from those in described pathways of non-canonical NF-kB activation via ligand:receptor interactions.

Our current areas of research include: 1) determining endosome-associated signaling components(s) required for complement to activate non-canonical NF-kB, 2) identifying how non-canonical NF-kB initiates downstream pro-inflammatory pathway(s) including inflammasome assembly, and 3) understanding how complement-treated endothelial cells potentiate alloimmune CD4+ T cell activation. We have a number of ongoing translational projects in each of these areas that are very exciting. Please do not hesitate to contact me to speak if you have an interest in any of the above.

Selected Publications

See list of PubMed publications

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