Dr. Murphy Research Lab
Professor and Acting Chair
Department of Dermatology
Department of Internal Medicine
Division of Hematology/Oncology
Research Interests: Cancer Immunotherapy
and graft vs host disease.
UC Davis Department of Dermatology
2921 Stockton Blvd.
Sacramento, CA 95716
Dr. Murphy spent his postdoctoral years and early career at the National Cancer Institute (NCI) in Frederick, Maryland. After 12 years, and becoming Director of Basic Research at NCI-Frederick in Maryland, he joined the faculty at the University of Nevada, Reno (UNR). Dr. Murphy later became the Chair of Microbiology and Immunology at UNR, School of Medicine. In 2008, Dr. Murphy moved his laboratory to UC Davis, accepting a position as Professor and Vice Chair of Research in the Department of Dermatology and Internal Medicine, Division of Hematology Oncology.
The immune system can both fight cancer and promote it during chronic inflammatory conditions. Understanding the complex immunology of cancer will lead to better means of preventing and treating it.
Dr. Murphy’s laboratory studies various aspects within cancer immunology and immunotherapy for melanoma. Current projects within the lab are exploring how to increase the success of these engraftments as well as to make them safer for patients by decreasing the period in which the patient is immune-compromised. Another focus within Dr. Murphy’s laboratory is studying how the immune system becomes activated after the systemic administration of immunotherapies. His laboratory has several NIH R01 grants and is also funded by CIRM, looking at stem cell engraftment.
Dr. Murphy has over 200 publications in cancer immunology over his 25 year career and is active on multiple NIH Study Sections.
Undergraduate Education: Rutgers University, New Brunswick, New Jersey, B.S. 1984
Graduate Education: University of Texas, Southwestern Medical School, Dallas, Texas, Ph.D. 1989
Left to right (standing):
Catherine Le, GSR
Jacob Mathai, Student
Steven Grossenbacher, GSR
Ian Sturgill, Junior Specialist
Jane (Qian) Chen, SRA
Ethan Aguilar, GSR
Dr. William Murphy, Professor
Sita Withers, DVM (Visiting PhD Student)
Monja Metcalf, SRA Supervisor
Lam Khuat, GSR
Christine Mall Minnar, PhD
Left to right (sitting):
Cordelia Dunai, GSR
Stefani (Ziming) Wang, GSR
Weihong Ma, SRA
Bone marrow transplantation (BMT) is currently used for the treatment of a variety of disease states ranging from aplastic anemia to cancer. However, significant obstacles limit the efficacy of this procedure. These include: marrow graft failure, graft-versus-host disease (GVHD), immune deficiency following the transplant, and when used for the treatment of cancer, relapse of the tumor. Using both in vivo and in vitro model systems, our laboratory has been examining the immunobiology underlying these obstacles.
Natural killer (NK) cells have been demonstrated to be responsible for mediating the specific rejection of bone marrow cell (BMC) allografts in lethally irradiated mice. However, little is known concerning the nature of these cells and BMC rejection which leads to marrow graft failure. We have found that NK cell subsets exist that are responsible for mediating the specific rejection of BMC from mice bearing the appropriate MHC molecules. In addition, these NK subsets also play an important role in the normal homeostasis of hematopoiesis suggesting that it is one of their normal physiologic functions. We are currently examining the differentiation of these various subsets. We are also using activated NK cells as a means of providing additional antitumor effects when BMT is used with tumor bearing mice. We found that adoptive transfer of NK cells can provide significant antitumor effects while at the same time promoting hematopoietic engraftment and preventing GVHD in mice. We are currently examining the mechanism(s) by underlying these effects.
Our laboratory has also been examining means to accelerate immune and hematopoietic reconstitution following BMT. This would also be of use in other instances where immune recovery is desirable such as in AIDS. We have been focusing on the use of neuroendocrine hormones such as growth hormone (GH) and prolactin. They are attractive since they are relatively nontoxic when given systemically and can exert pleiotropic effects. We have found that GH can exert significant hematopoietic growth-promoting effects after in vivo administration. GH can also accelerate immune and hematopoietic reconstitution after BMT in mice. Using a human/mouse chimera model we have found that these hormones can improve human T-cell trafficking and function in vivo. We are also examining physiological role of these neuroimmune interactions.
Another problem with BMT is an EBV-induced B-cell lymphoma that can arise in immunodeficient individuals. We have found that stimulation of CD40, a molecule present on B cells critical for their development and function, can promote B-cell recovery after BMT. Using a human/mouse chimera model, we have also found that CD40 stimulation can prevent the occurrence of this EBV-induced B-cell lymphoma in vivo. Thus, CD40 stimulation after BMT may accelerate immune recovery and prevent lymphoma generation. We are currently examining the role of CD40 in hematopoiesis.
- Alderson KL, Murphy WJ. 2009. Effects of cancer immunotherapy regimens on primary vs. secondary immune responses and the potential impact on long-term antitumor responses. Adv Exp Med Biol: Crossroads Between Innate and Adaptive Immunity II, ed. 633: 81-89.
- Ames E, Hallett WD, Murphy WJ. 2009. Sensitization of human breast cancer cells to natural killer cell-mediated cytotoxicity by proteasome inhibition. Clin Exper Immunol 155: 504-13.
- O'Shaughnessy MJ, Vogtenhuber C, Sun K, Sitcheran R, Baldwin AS, Murphy WJ., Dang L, Jaffee B, Palmer E, Serody JS, Blazar BR. 2009. Ex vivo inhibition of NK-kappaB signaling in alloreactive T-cells prevents graft-versus-host disease. Am J Transplant 9: 452-62.
- Taylor PA, Ehrhardt MJ, Lees CJ, Panoskaltsis-Mortari A, Krieg AM, Sharpe AH, Murphy WJ., Serody JS, Hemmi H, Akira S, Levy RB, Blazar BR. 2008. TLR agonists regulate alloresponses and uncover a critical role for donor APCs in allogeneic bone marrow rejection. Blood 112:3508-16.
- Sun K, Li M, Sayers TJ, Welniak LA, Murphy WJ.. 2008. Differential effects of donor T cell cytokines on outcome with continuous bortezomib administration following allogeneic bone marrow transplantation. Blood 112: 1522-9.
- Shanker A, Brooks AD, Tristan CA, Wine JW, Elliott PJ, Yagita H, Takeda K, Smyth MJ, Murphy WJ, Sayers TJ. 2008. Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody. J Natl Cancer Inst 100: 649-62.
- Redelman D, Welniak LA, Taub D, Murphy WJ. 2008. Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network. Cell Immunol 252: 111-21.
- Puliaev R, Puliaeva I, Welniak LA, Ryan AE, Haas M, Murphy WJ, Via CS. 2008. CTL-Promoting Effects of CD40 Stimulation Outweigh B Cell-Stimulatory Effects Resulting in B Cell Elimination and Disease Improvement in a Murine Model of Lupus. J Immunol 181: 47-61.
- Murphy WJ. 2008. Raising the specta of T-cell profiling. Blood 112: 3008-9.
- Motarjemi M, Hallett WHD, Li M, Murphy WJ. 2008. Proteasome Inhibition: Potential for Sensitization of Immune Effector Mechanisms in Cancer. In Sensitization of Cancer Cells for Chemo/immuno/Radio-therapy., ed. B Bonavida, pp. 51-60. Totowa, NJ: Humana Press