Primary Appointment:
 Environmental Medicine

GEBS Cluster Affiliations:
 Immunology, Microbiology, and Virology - IMV
 Toxicology - TOX

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 704
Rochester, New York 14642

MRBX 3-11104
Phone: (585) 275-8326
E-Mail: richard_phipps@urmc.rochester.edu

Role of prostaglandins in immunity and as anti-cancer agents: Prostaglandins (PG) are small lipid mediators that control inflammation and regulate the immune system. This laboratory studies how PG of the E and J series regulate B and T lymphocytes. PGE2 promotes allergy and antibody production to IgE, in part by inhibiting the synthesis of type-1 cytokines. PGJ2 binds to a nuclear receptor and can induce cell death in normal and malignant B and T lineage cells. PGJ2 is currently thought to have potent anti-inflammatory effects owing to its ability to dampen immune responses. These PGs have very different regulatory effects on immunity. Current efforts are focusing on the genes that PGE2 induces to skew immune responses towards antibody synthesis and allergy and on the molecular pathways where PGJ2 kills normal and malignant B and T lineage cells.

Fibroblasts as mediators of lung inflammation, wound healing and fibrosis: Injury to the lung from exposure to chemotherapeutic agents, irradiation, or occupational hazards such as mineral dusts, may lead to pulmonary fibrosis. The advanced stages of this disease are characterized by a fibroblast hyperplasia and by excessive accumulation of fibroblast-secreted connective tissue such as collagen. This laboratory is investigating the molecular pathways of fibroblast activation and their role in inflammation. We discovered that CD40 is a key activation receptor for human fibroblasts. The CD40 ligand is found on activated T cells, mast cells and eosinophils and permit fibroblast-immune cell communication and mutual activation. Current efforts are determining the signal transduction pathways of CD40 and testing preclinical models of lung disease to ascertain the importance of the CD40/CD40 ligand system.

Akbiyik F, Ray DM, Gettings KF, Blumberg N, Francis CW, Phipps RP. Human bone marrow megakaryocytes and platelets express PPAR{gamma} and PPAR{gamma} agonists blunt platelet release of CD40 ligand and thromboxanes. Blood. 2004 May 6 [Epub ahead of print]

Kaufman J, Sime PJ, Phipps RP. Expression of CD154 (CD40 ligand) by human lung fibroblasts: differential regulation by IFN-gamma and IL-13, and implications for fibrosis. J Immunol. 172:1862-71, 2004.

Phipps RP, Ryan E, Bernstein SH. Inhibition of cyclooxygenase-2: a new targeted therapy for B-cell lymphoma? Leuk Res. 28:109-11, 2004.

Koumas L, Smith TJ, Feldon S, Blumberg N, Phipps RP. Thy-1 expression in human fibroblast subsets defines myofibroblastic or lipofibroblastic phenotypes. Am J Pathol. 163:1291-300, 2003.

Blumberg N, Phipps RP, Kaufman J, Heal JM. The causes and treatment of reactions to platelet transfusions. Transfusion. 43:291-292, 2003.

Smith RS, Kelly R, Iglewski BH, Phipps RP. The Pseudomonas autoinducer N-(3-oxododecanoyl) homoserine lactone induces cyclooxygenase-2 and prostaglandin E2 production in human lung fibroblasts: implications for inflammation. J Immunol. 169:2636-42, 2002.

Koumas L, Phipps RP. Differential COX localization and PG release in Thy-1(+) and Thy-1(-) human female reproductive tract fibroblasts. Am J Physiol Cell Physiol. 283:C599-608, 2002.

Padilla J, Leung E, Phipps RP. Human B lymphocytes and B lymphomas express PPAR-gamma and are killed by PPAR-gamma agonists. Clin Immunol. 103:22-33, 2002.

Harris SG, Padilla J, Koumas L, Ray D, Phipps RP. Prostaglandins as modulators of immunity. Trends Immunol. 23:144-50, 2002. Review.

Harris SG, Phipps RP. Prostaglandin D(2), its metabolite 15-d-PGJ(2), and peroxisome proliferator activated receptor-gamma agonists induce apoptosis in transformed, but not normal, human T lineage cells. Immunology. 105:23-34, 2002.

Koumas L, Smith TJ, Phipps RP. Fibroblast subsets in the human orbit: Thy-1+ and Thy-1- subpopulations exhibit distinct phenotypes. Eur J Immunol. 32:477-85, 2002.

Harris SG, Smith RS, Phipps RP. 15-deoxy-Delta 12,14-PGJ2 induces IL-8 production in human T cells by a mitogen-activated protein kinase pathway. J Immunol. 168:1372-9, 2002.

Phipps RP, Kaufman J, Blumberg N. Platelet derived CD154 (CD40 ligand) and febrile responses to transfusion. Lancet. 357:2023-4, 2001.