Wayne William Hancock

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
Lab: (215) 900-4806
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 of Pathologists of Australasia, 1989.
Post-Graduate Training
Intern in Medicine , Alfred Hospital, Mebourne, Australia, 1977-1978.
Resident in Medicine, Alfred Hospital , Mebourne, Australia, 1978-1979.
Pathology Fellow , Prince Henry's Hospital, Melbourne, Australia, 1980-1983.
Research Fellowship, Pathology, Brigham and Women's Hospital, Boston, MA, 1984-1986.
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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

Description of Itmat Expertise

Transplantation
Autoimmunity
Tolerance
Epigenetics
Therapeutics
HDAC inhibitors
HAT inhibitors
DNMT inhibitors

Selected Publications

Cravedi P, Riella LV, Ford M, Valujskikh A, Menon MC, Kirk AD, Alegre ML, Feng S, Kehn P, Najafian N, Hancock W, Heeger PS, Maltzman J, Mannon RB, Nadig S, Odim J, Turnquist H, Shaw J, West L, Luo X, Chong A, Bromberg J, on behalf of the AST COTS MOuse MOdels in Transplantation (MOMOT) work group.: Advancing mouse models for transplantation research. American Journal of Transplantation Page: https://doi.org/10.1016/j.ajt.2024.01.006, January 2024.

Concors SJ, Hernandez PT, O’Brien C, DePaolo J, Murken DR, Aufhauser DD, Wang Z, Xiong Y, Krumeich L, Ge G, Beier UH, Bhatti TR, Kozikowski AP, Avelar L, Kurz T, Hancock WW, Levine MH. : Differential effects of HDAC6 inhibition versus knockout during hepatic ischemia reperfusion injury highlight importance of HDAC6 C-terminal zinc-finger ubiquitin-binding domain. Transplantation Page: In press, 2024.

Thomas RM, Pahl MC, Wang L, Grant SFA, Hancock WW, Wells AD.: Foxp3 depends on Ikaros for control of regulatory T cell gene expression and function. eLife Page: In press, 2024.

Patterson KC, Miller WT, Hancock WW, Akimova T.: FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis. Frontiers in Immunology 14: 1301991, December 2023.

Lax E, Do Carmo S, Enuka Y, Sapozhnikov DM, Welikovitch LA, Mahmood N, Rabbani SA, Wang L, Britt JP, Hancock WW, Yarden Y, Szyf M. : Methyl-CpG binding domain 2 (Mbd2) is an epigenetic regulator of autism-risk genes and cognition. Translational Psychiatry 13: 259, July 2023.

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.

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.

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Last updated: 03/10/2024
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