Australasia Extracellular Vesicles Conference31 January - 2 February, 2017 Lorne, Vic

Professor Philip Askenase

Dr Askenase played basketball at Brown University and then emerged as a Junior Phi Beta Kappa scholar, then on to Yale Medical School, Medicine Residency in at the Boston City Hospital Harvard unit, fellowships at the National institutes of Health in Bethesda, Maryland and then in London,England.  Returning to Yale Medical School he ecame a tenured Professor in Medicine and the Chief of Allergy and Clinical Immunology. 

During more than a 50 year career, his research uncovered the late phase inflammation component of asthma that is susceptible to steroid treatment, and discovered the essential roles of allergy mechanisms in responses to parasites and in general underlying T cell mediated immunity. In recent work he has demonstrated the power of previously unknown nano vesicle exosomes to specifically transfer gene altering RNAs between cells in allergy, immunity and treatment of injuries of the central nervous system. Clinically, he founded the AIDs clinic at Yale and participated in the discovery of Lyme Disease.

Brief Past Research Summary:

Dissection of crucial cellular and molecular interactions guiding the traffic and eventual recruitment of antigen-specific T cells, out of the blood vessels, and into the tissues, at specific sites of immune reactivity, such as allergic responses (asthma) or protective responses, expulsion of helminth worms from the GI tract, or ticks from the skin.

Determination that micro-mediators, such as serotonin and leukotrienes, released by mediator-containing cells, such as mast cells or platelets, are of crucial importance in alteration of the local vasculature to allow penetration into the tissues by antigen-specific T cells, that arrive and interact with local antigen-presenting cells that present relevant peptides of antigens, causing release of cytokines by the T cells, to mediate local inflammation and allergy, or in contrast, immune protection and resistance.

Current Research Description: 

T Cell Mediated Suppression via miRNA Intercellular Delivered Nanovesicle Exospores. Currently our laboratory is totally dedicated to study of exosomes; particularly as treatment via our discoveries that an antibody light chain coat and miRNA content can be chosen for Ag-specific targeting for transfer of particular epigenetic alterations in selected recipient targeted cells, here via transfer inhibitory of miRNA-150, and targeting by the Ag-specific suppressive exosomes to specific Ag-presenting cells  via their surface Ag peptide complexed in MHC on the surface of APC that is bound by the Ab on the surface of suppressive exosomes-derived from CD8+ T suppressor cells, to inhibit the target effector T cells by producing secondary suppressive exosomes inhibiting CS in an Ag/MHC-dependent manner and in ovalbumin-specific DTH. We recently have written the first and thus the only review on the Functions of Exosomes and Microbial Outer Membrane Vesicles in Allergy, Contact and Delayed-Type Hypersensitivity (Int Arch All and Appl Immunol, vol 171:1-26, 2016;  DOI:10.1159/000449249).

Mediation of healing of spinal cord injury (SCI) by exosomes derived from mesenchymal stem cells (MSC). Provisionally, using fluorescent labeled mesenchymal stem cell-derived exosomes for systemic therapy of traumatic spinal cord injury (SCI), we have show that the effect likely is due to very specific exosome targeting of M2-type healing macrophages.

SCI resulted in profound weakness and large vascular leakage that were reduced in MSC transplanted rats beginning 1 week post-MSC infusion.  However, i.v infused MSCs were not detected within the spinal cord at any time point, but appeared to traffic just transiently to the lungs. In contrast, MSCexos produced comparable improvements and were readily detected at sites of SCI; especially localizing to M2 macrophages (Macs) associated with healing vs. pro-inflammatory M1 Macs.

Summary: The data suggest that the therapeutic effect of MSCs on SCI likely is mediated by their secreted MSCexos that preferentially target healing M2 and not inflammatory M1 macrophages.