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Wayne William Hancock, MB.BS, PhD, FRCPA

Wayne William Hancock, MB.BS, PhD, FRCPA

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Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
916B Abramson Research Center
3615 Civic Center Blvd.
Philadelphia, PA 19104-4318
Office: (215) 590-8709
Fax: (215) 590-7384
Education:
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

Jiao J, Han R, Hancock WW, Beier UH. : Proximity ligation assay to quantify Foxp3 acetylation in regulatory T cells. Methods in Molecular Biology 1510: 287-293, January 2017.

Woods DM, Woan K, Wang D, Sodré AL, Cheng F, Wang Z, Chen J, Powers J, Pinilla-Ibarz J, Yu Y, Weber J, Hancock WW, Seto E, Villagra A, Yu XZ, Sotomayor EM.: Histone deacetylase 11 is an epigenetic regulator of Eomes and Tbet expression in T-cells. Blood In press, 2017.

Angelin A, De Gomez LG, Dahiya S, Jiao J, Guo L, Wang L, Akimova T, Liu Y, Bhatti TR, Han R, Wang W, Laskin BL, Blair IA, Wallace DC, Hancock WW, Beier UH. : Foxp3 reprograms T cell metabolism to function in low glucose high lactate environments. Cell Metabolism In press, 2017.

Lama VN, Belperio JA, Christie JD, El-Chemaly S, Fishbein MC, Gelman AE, Hancock WW, Keshavjee S, Kreisel D, Laubach VE, Looney MR, McDyer JF, Mohanakumar T, Shilling RA, Panoskaltsis-Mortari A, Wilkes DS, Eu JP, Nicolls MR.: NHLBI Workshop Report: Animal Models of Lung Transplant Research JCI Insight In press, 2017.

Wang L, Kumar S, Dahiya S, Wang F, Wu J, Newick K, Han R, Samanta A, Beier UH, Akimova T, Bhatti TR, Nicholson B, Kodrasov MP, Agarwal S, Sterner DE, Gu W, Weinstock J, Butt TR, Albelda SM, Hancock WW.: Ubiquitin-specific Protease-7 Inhibition Impairs Tip60-dependent Foxp3+ T-regulatory Cell Function and Promotes Antitumor Immunity. EBioMedicine 13: 99-112, November 2016.

Hancock WW. : Isoform-selective HDAC inhibitor therapy for transplantation: Are we ready for HDAC6? Transplantation 100(8): 1597-98, August 2016.

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 1371: 43-78, July 2016.

Singhal S, Bhojnagarwala PS, O'Brien S, Moon EK, Garfall AL, Rao AS, Quatromoni JG, Stephen TL, Litzky L, Deshpande C, Feldman MD, Hancock WW, Conejo-Garcia JR, Albelda SM, Eruslanov EB.: Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer. Cancer Cell 30(1): 120-135, July 2016.

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 89(5): 1016-1026, May 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 126(5): 1968-1977, May 2016.

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Last updated: 08/29/2017
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