Lawrence Pfeffer, Ph.D., Professor and Acting Chair
Department of Pathology

IFNs are multifunctional proteins that also regulate cell proliferation, cell differentiation, apoptosis (programmed cell death) and activities of the immune system. IFNs are clinically useful in diseases of diverse pathogenesis and manifestations- hairy cell leukemia, Kaposi's sarcoma, laryngeal and genital papillomas, chronic viral hepatitis, and multiple sclerosis. Understanding the molecular basis of IFN action is an important goal when one considers IFN’s therapeutic potential in cancer, viral hepatitis, and multiple sclerosis, as well as its role as a model for understanding cytokine signal transduction.

In a series of studies over the last few years, Dr. Pfeffer's laboratory has made the important finding that STAT3 plays a critical role in IFNa signal transduction and induction of biological actions. STAT3, the transcription factor for acute phase response genes, is activated by a wide variety of cytokines suggesting that it may integrate diverse signals into common transcriptional responses. By microarray analysis Dr. Pfeffer has identified several “new” IFN-induced genes, whose pathways of regulation we will examine in the future. Some of these IFN-regulated genes play important roles in cell cycle control and cell survival. While others will provide exciting new avenues of investigation for IFN signaling and action. For example, IFN has anti-angiogenic activity and we have found that expression of angiopoietin-2 (an angiogenic gene) is down-regulated by IFN, while thrombospondin-1 (an anti-angiogenic gene) expression is upregulated by IFN

Recent Publications

Polyamine depletion induces rapid NF-kappa B activation in IEC-6 cells. Pfeffer LM, Yang CH, Murti A, McCormack SA, Viar MJ, Ray RM, Johnson LR. J Biol Chem 276(49):45909-13, 2001.

Interferon alpha /beta promotes cell survival by activating nuclear factor kappa B through phosphatidylinositol 3-kinase and Akt. Yang CH, Murti A, Pfeffer SR, Kim JG, Donner DB, Pfeffer LM. J Biol Chem 276(17):13756-61, 2001.

IFNalpha/beta promotes cell survival by activating NF-kappa B. Yang CH, Murti A, Pfeffer SR, Basu L, Kim JG, Pfeffer LM. Proc Natl Acad Sci 97(25):13631-6, 2000.

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