Wayne William Hancock, MB.BS, PhD, FRCPA

faculty photo
Professor of Pathology and Laboratory Medicine
Investigator, Biesecker Pediatric Liver Center, The Children's Hospital of Philadelphia
Member, Penn Diabetes Center, U Penn
Member, Abramson Cancer Center, U Penn
Chief, Division of Transplantation Immunology, Children's Hospital of Philadelphia
Member, Penn Center for Clinical Immunology, U Penn
Member, Penn Cardiovascular Center, U Penn
Member, Institute for Translational Medicine and Therapeutics, U Penn
Member, Rheumatic Diseases Core Center, U Penn/CHOP
Member, Institute for Immunology, U Penn
Member, Penn Program in Epigenetics
Member, Penn-CHOP Lung Biology Institute
Member, Institute for RNA Innovation, University of Pennsylvania
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
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 of Pathologists of Australasia, 1989.
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Description of Research Expertise

Research Interests

Transplant immunobiology, inflammation and mechanisms of disease, Treg cells, cancer immunology, therapeutics

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.

See: http://www.hancocklab.net

Selected Publications

Hernandez P, O’Brien C, Concors SJ, Wang Z, Ge G, Hancock WW, Levine MH. : The selective estrogen receptor modulator, Raloxifene, is protective against renal ischemia reperfusion injury. Transplantation 106: 2166-2171, November 2022.

Graham ML, Ramachandran S, Singh A, Moore MEG, Flanagan EB, Azimzadeh A, Burlak C, Mueller KR, Martins K, Anazawa T, Balamurugan AN, Bansal-Pakala P, Murtaugh MP, O’Brien TD, Papas KK, Spizzo T, Schuurman HJ, Hancock WW, Hering BJ.: Clinically available immunosuppression with tacrolimus combined with basiliximab, rapamycin and CTLA4Ig averts rejection but not systemic inflammation after porcine islet xenotransplant in cynomolgus macaques. American Journal of Transplantation 22: 745-760, March 2022.

Siska PJ, Jiao J, Matos C, Singer K, Dettmer K, Oefner PJ, Cully MD, Wang Z, Oliff KN, Wilkins BJ, Christensen LM, Wang L, Hancock WW, Baur JA, Levine MH, Ugele I, Mayr R, Renner K, Zhou L, Kreutz M, Beier UH.: Kynurenine induces T cell fat catabolism and has limited suppressive effects in vivo. EBioMedicine 74: 103734, December 2021.

Akimova T, Zhang T, Christensen LM, Wang Z, Han R, Negorev D, Samanta A, Sasson IE, Gaddapara T, Jiao J, Wang L, Bhatti TR, Levine MH, Diamond JM, Beier UH, Simmons RA, Cantu E, Wilkes DS, Lederer DJ, Anderson M, Christie JD, Hancock WW.: Obesity-related IL-18 impairs Treg function and promotes lung ischemia-reperfusion injury. American Journal of Respiratory and Critical Care Medicine 204: 1060-1074, November 2021.

Di Giorgio E, Wang L, Xiong Y, Christensen LM, Akimova T, Han R, Samanta A, Trevisanut M, Brancolini C, Beier UH, Hancock WW.: A biological circuit involving Mef2c, Mef2d and Hdac9 controls the immunosuppressive functions of CD4+Foxp3+ T-regulatory cells. Frontiers in Immunology 12: 703632, July 2021.

Aufhauser DD, Wang Z, Murken DR, Samanta A, Concors SJ, Bhatti TR, Wang Y, Ge G, Wang L, Cheraghlou S, Wagner FH, Holson EB, Kalin JH, Cole PA, Hancock WW, Levine MH.: HDAC2 targeting stabilizes the CoREST complex in renal tubular cells and protects against renal ischemia/reperfusion injury. Scientific Reports 11: 9018, April 2021.

Di Giorgio E, Wang L, Xiong Y, Akimova T, Christensen LM, Han R, Samanta A, Trevisanut M, Bhatti TR, Beier UH, Hancock WW.: MEF2D sustains activation of effector Foxp3+ Tregs during transplant survival and anticancer immunity. Journal of Clinical Investigation 130: 6242-6260, December 2020.

Quinn WJ 3rd, Jiao J, TeSlaa T, Stadanlick J, Wang Z, Wang L, Akimova T, Angelin A, Schäfer PM, Cully MD, Perry C, Kopinski PK, Guo L, Blair IA, Ghanem LR, Leibowitz MS, Hancock WW, Moon EK, Levine MH, Eruslanov EB, Wallace DC, Baur JA, Beier UH.: Lactate Limits T Cell Proliferation via the NAD(H) Redox State. Cell Reports 33: 108500, December 2020.

Mittal P, Wang L, Akimova T, Leach CA, Clemente JC, Sender MR, Chen Y, Turunen BJ, Hancock WW.: The CCR2/MCP-1 Chemokine Pathway and Lung Adenocarcinoma. Cancers 12: 3723, December 2020.

Xu H, Steinberger Z, Wang L, Han R, Zhang Y, Hancock WW, Levin LS.: Limited efficacy of rapamycin monotherapy in vascularized composite allotransplantation. Transplant Immunology 61, August 2020.

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Last updated: 03/22/2023
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