Steven D. Douglas, M.D.
Professor of Pediatrics and Microbiology

Gene Therapy and Vaccines Program

Address

The Children's Hospital of Philadelphia
Suite 1208 Abramson Research Building
34th and Civic Center Boulevard
Philadelphia, PA 19104-4399

Office tel.: 215 590-1978
Lab tel.: 215 590-1991
Fax: 215 590-3044
E-mail: douglas@email.chop.edu


Education

Cornell University: AB (Zoology), 1959.

Cornell University Medical School: MD, 1964.

University of California, San Francisco: Postdoctoral Fellow (Immunology), 1967-1969.

Research Interests

• Psychoneuroimmunology, interaction between immune system and stress, alcohol and HIV, Neurokinin-1R (SP Receptor) Antagonists for HIV Therapy.

Key words: Substance P, psychoneuroimmunology.

Search PubMed for articles

Description of Research

Steven D. Douglas, M.D., Chief of the Section of Immunology, Professor of Pediatrics, The Children’s Hospital of Philadelphia, has been analyzing neurokinin-1 receptors found on the surfaces of monocytes, immune cells that develop into macrophages. The neurokinin-1 receptors (NK-1R) are docking sites for substance P, a well-known neurotransmitter that plays important roles in both immune function and the nervous system. Dr. Douglas has been investigating substance P, a neurotransmitter long known to be active in the brain and nervous system. He and colleagues discovered in 1997, that immune cells produce substance P and its receptor, neurokinin-1, and later showed that incubation with substance P raised HIV levels in immune cell cultures. They subsequently found that a compound that binds to the substance P receptor in immune cells, inhibits HIV from entering its hiding place within immune cells. Dr. Douglas’ team investigated two forms of NK-1R in a human monocyte/macrophage cell line. One is the full-length receptor, and the other a shortened version with fewer amino acids with the addition of substance P to cell cultures, the cells both responded with an increase in calcium ions, but used distinct signaling pathways. New HIV-l therapies that utilize novel antiviral mechanisms and exert a positive immunomodulatory effect are needed. Neurokinin-l receptor (NK-1R) antagonists target the substance P (SP) receptor and have demonstrated antiviral and immunomodulatory effects. The NK- 1 R antagonists are a new therapeutic target with the potential to interrupt a pathway critical to HIV replication.

Dr. Douglas is a member of the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network Executive Committee, which sets the scientific agenda. He is also the Principal Investigator for the IMPAACT Clinical Trials Unit, the Director for the IMPAACT Core Immunology Laboratory, of which its major goals are to perform assays for the Pediatric ACTG clinical trials; and the Principal Investigator of the Specialty Immunology Laboratory for IMPAACT. The Immunology Laboratory performs research assays and developmental assay work in support of the IMPAACT scientific agenda related to monitoring and characterizing immune restoration in response to antiviral or immune-based therapies, including vaccines.

Recent Publications

Ho, W-Z, Lai, J-P, Zhu, X-H, Uvaydova, M., and Douglas S.D. Human monocytes and macrophages express substance P and neurokinin-1 receptor. J. Immunol. 159:5654-5660, 1997.

Lai, J-P, Ho, W-Z, Zhan, G-X, Yi, Y., Collman, R.G. and Douglas, S.D.: Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes. Proc. Natl. Acad. Sci. U. S. A. 98:3970-3975, 2001.

Ho WZ, Lai JP, Li Y, Douglas SD.; HIV enhances substance P expression in human immune cells. FASEB J 2002 Apr;16(6):616-8.

Lai, J.P., Ho, W.Z., Kilpatrick, L.E., Wang. X., Tuluc, F., Korchak, H.M., and Douglas, S.D. Full-Length and Truncated Neurokinin-1 Receptor (NK-1R) Expression and Function during Monocyte-Macrophage Differentiation. Proc. Nat. Acad. Sci. U. S. A. 130:7771-7776, 2006.

Lab

Rotation Projects

Determined on an individual basis.

Lab personnel:

Wenzhe Ho, M.D., Research Professor of Pediatrics
Jian Ping Lai, M.D., Research Associate
Florin Tuluc, M.D., Ph.D., Scientist