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Wayne William Hancock

Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine

Contact information
916B Abramson Research Center
3615 Civic Center Blvd.
Philadelphia, PA 19104-4318
Office: (215) 590-8709
Fax: (215) 590-7384
Graduate Group Affiliations
M.B.B.S. (Medicine)
Monash University, Clayton, Victoria, Australia, 1977.
Ph.D. (Medicine)
Monash University, Clayton, Victoria, Australia, 1984.
F.R.C.P.A. (Pathology)
Royal College o fPathologists of Australasia, 1989.
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Description of Research Expertise

Research Interests

Transplant immunobiology, inflammation and mechanisms of disease

Research Summary

New Co-Stimulation Molecules And Their Function In Vivo
The world is currently awash with costimulation molecules. Individual labs tout this or that molecule as being key to T cell activation under specific (often ludicrously specific) conditions, but none of these "insights" have yet led to actual therapeutic agents in clinical use. This reflects several factors. Drug companies make drugs and then try and find an application for them, ideally rheumatoid arthritis, multiple sclerosis, asthma or some other widespread disease involving long-term therapy, but certainly not any of the indications subject to the "too small a market (e.g. <$200 million dollars/year)" rule. Biologics are difficult and expensive to develop. Hence, the science underlying all the costimulation hype needs to examined critically if progress is to be achieved. Rather than adding more and more costimulation molecules to the list and thinking they are all equally important such that the Immunology Today-type diagrams in peoples' minds becomes more and more complicated, some reality testing is called for, and may thereby lead to new therapeutic approaches. Transplant models provide particularly advantageous systems to test the importance of such costimulation pathways using knockouts and blocking monoclonal antibodies and fusion proteins. We are currently investigating ICOS/B&RP-1; PD-1 and its ligands, PD-L1 and PD-L2; B7-H3; BTLA and B7-H4; and several TNF/TNF-R superfamily pathways, i.e. those molecules which constitute the "next wave" on which immunologic hopes, careers and dreams typically seem to be pinned upon but which in this case, as a bonus, may also be "true".

Chemokines/chemokine receptors in allograft rejection vs. tolerance
If all the world is a stage than an organ transplant is from an immunologic perspective a gothic masterpiece wherein every component of the immune system boils and pokes its way into the limelight at some point or another and the challenge is to make sense of it all. Chemokines are small molecular weight chemotactic cytokines which bind and signal via G protein-coupled seven-transmembrane receptors expressed by most cell types. Of special interest to immunologists are those chemokine receptors which mediate T cell recirculation as well as those which mediate attraction to sites of immune stimulation, such as an organ transplant. This field has its problems, not the least of which is its dreaded new nomenclature which has only served to decrease rather than improve communication. Suffice to say that despite there being over 45 chemokines and at least 18 chemokine receptors, with countless assertions of biologic redundancy and "promiscuous" binding (which sound interesting but isn't in this case), the development and testing of knockout mice and availability of neutralizing mAbs for use in wild-type controls has provided some sense of insight into how these pathways work in vivo. Of the various pathways involved in allograft responses, the most important seems to be CXCR3, which is expressed by NK cells and activated T cells, and has 3 ligands: IP-10, Mig and I-TAC. Blockade of CXCR3 has a particularly powerful effect in reducing host alloresponses. The second most important appears to be CCR5, whose ligands are many but include MIP-1a, MIP-1b and RANTES. We continue to investigate the importance of these and additional chemokine/chemokine receptor pathways in experimental and clinical studies.

Selected Publications

Levine MH, Wang Z, Xiao H, Jiao J, Wang L, Bhatti TR, Hancock WW, Beier UH.. : Targeting Sirtuin-1 prolongs murine renal allograft survival and function. Kidney International Page: In press, 2016.

Jiao J, Han R, Hancock WW, Beier UH. : Proximity ligation assay to quantify Foxp3 acetylation in regulatory T cells. Methods in Molecular Biology Page: In press, 2016.

Aufhauser DA, Wang Z, Bhatti TR, Wang Y, Ge G, Redfield RR, Abt PL, Wang L, Thomasson A, Reese P, Hancock WW, Levine MH. : Improved renal ischemia tolerance in females influences kidney transplantation outcomes. Journal of Clinical Investigation Page: In press, 2016.

Hancock WW. : Isoform-selective HDAC inhibitor therapy for transplantation: Are we ready for HDAC6? Transplantation Page: In press, 2016.

Xiao H, Jiao J, Wang L, O'Brien S, Newick K, Wang LS, Falkensammer E, Liu Y, Han R, Kapoor V, Hansen FK, Kurz T, Hancock WW, Beier UH.: HDAC5 controls the functions of Foxp3+ T-regulatory and CD8+ T cells. Int J Cancer. Page: doi: 10.1002/ijc.29979. [Epub ahead of print] December 2015.

Segretti MCF, Vallerini GP, Brochier C, Langley B, Wang L, Hancock WW, Kozikowski AP. : Thiol-based potent and selective HDAC6 inhibitors promote tubulin acetylation and T‑regulatory cell suppressive function. ACS Medicinal Chemistry Letters 5: 1156-1161, October 2015.

Deng G, Nagai Y, Xiao Y, Li Z, Dai S, Ohtani T, Banham AH, Li B, Wu SL, Hancock W, Samanta A, Zhang H, Greene MI. : Pim-2 kinase influences T-regulatory cell function and stability by mediating Foxp3 N-terminal phosphorylation. Journal of Biological Chemistry 290: 20211-20220, August 2015.

Fouraschen SM, Wolf JH, van der Laan LJ, de Ruiter PE, Hancock WW, van Kooten JP, Verstegen MM, Olthoff KM, de Jonge J. : Mesenchymal stromal cell-derived factors promote tissue repair in a small-for-size ischemic liver model but do not protect against early effects of ischemia and reperfusion injury. Journal of Immunologic Research 2015: 202975, August 2015.

Akimova T, Levine MH, Beier UH, Hancock WW. : Standardization, evaluation and area-under-curve analysis of human and murine Treg suppressive function. Methods in Molecular Biology In press, July 2015.

Beier UH, Angelin A, Akimova T, Wang L, Liu Y, Xiao H, Koike MA, Hancock SA, Bhatti TR, Han R, Jiao J, Veasey SC, Sims CA, Baur JA, Wallace DC, Hancock WW. : Essential role of mitochondrial energy metabolism in Foxp3+ T-regulatory cell function and allograft survival. FASEB Journal In press, June 2015.

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Last updated: 02/22/2016
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