primary immune deficiency
Dr. Douglas is developing new HIV-l therapies that utilize novel antiviral mechanisms, exert a positive immunomodulatory effect and have positive behavioral effects.
Interaction between immune system and brain and HIV, Neurokinin-1R (SP Receptor) Antagonists for HIV Therapy, HIV and NK1-R immune activation and suppression in psychiatric disease.
Key words: Substance P, Neurokinin-1 Receptor
Description of Research
Dr. Steven D. Douglas has been investigating cellular immune mechanisms and monocyte-macrophages. His laboratory is funded by a longstanding R01,Tachykinins Mononuclear Phagocytes and HIV-1 Infection. He is the PI for a U01, Anti-HIV Neuroimmunomodulatory Therapy with Neurokinin-1 Antagonists (NIMH) (through 2014), which encompasses three Projects (including a clinical trial) and two Cores (including Pharmacology and Biostatistics). He and his group investigate the interaction between neuropeptides, monocyte-macrophages and HIV. He is the Principal Investigator for the Philadelphia International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Unit, which includes a Clinical Research Site at CHOP, Clinical Research Site at the Adult Unit at the Hospital of the University of Pennsylvania, and two Satellites (Hospital of the University of Pennsylvania and Pennsylvania Hospital)(NIAID). Douglas? laboratory is the central immunology laboratory for the IMPAACT Network, and a specialty immunology laboratory. He is also the PI for the Adolescent Trial Network (NICHD). These networks are state-of-the-art therapeutic trials for adult and pediatric HIV/AIDS throughout the world. The Douglas laboratory does basic, translational, and clinical research.
Dr. Douglas' ongoing research program involves molecular and cellular immunologic studies of substance P and its receptor, Neurokinin-1 in monocyte-macrophages. He discovered the truncated from of NK1-R in human cells and demonstrated that SP antagonists block HIV through CCR5 and he has applied as NK1R antagonists novel HIV therapy. He has also demonstrated up-regulation of substance P by HIV. His laboratory is actively involved in research in cellular immunology and its relationship to the immunopathogenesis of HIV. Dr. Douglas has extensive experience in cellular and humoral immunologic studies, including studies of AIDS infection and of primary immunodeficiencies. He has recently instigated studies involving psychosocial and psychiatric interactions with the immune and nervous systems. Ongoing studies have demonstrated associations between substance P, impaired natural killer cell activity and depression in HIV-infected individuals.
Early in his career, Dr. Douglas discovered pokeweed mitogen as a lymphocyte stimulator and developed tests to diagnose immune deficiency diseases. He developed methods for isolation-differentiation of blood monocytes into macrophages and showed the role of macrophages in HIV. He detected SP-preferring receptor, neurokinin-1 (NK1R), in monocytes, and that SP antagonists inhibit HIV. He is testing NK1R antagonists as therapy for HIV patients.
Dr. Douglas has been President, Society for Leukocyte Biology. He has chaired committees for the VA, FDA (Blood Products Advisory Committee); and Chair NIH-CSR (AIDS Immunology Pathogenesis Study Section). He is the Founding Editor-in-Chief of Clinical and Diagnostic Laboratory Immunology, American Society Microbiology. He was the Recipient of Abbott Immunology, Neter, Conason, and Redway Awards. He is a Member ASCI, American Academy Microbiology, Honorary Life Member Society for Leukocyte Biology, Fellow AAAS.
Determined on an individual basis.
Mohammad Khan, MBBS, PhD, Senior Research Associate
John Meshki, PhD, Research Associate
Serguei Spitsin, Ph.D., Senior Research Associate
Florin Tuluc, M.D., Ph.D., Research Assistant Professor
Monaco-Shawver, L., Schwartz, L., Tuluc, F., Guo, CJ., Lai, JP, Gunnam, SM., Kilpatrick, LE, Banerjee, PP, Douglas, SD, Orange. Substance P inhibits natural killer cell cytotoxicity through the neurokinin-1 receptor. J Leukoc Biol. 2011 Jan;89(1):113-25.
Blume, J., Douglas, S.D., Evans, D.L.. Immune Suppression and Immune Activation in Depression. Review. Brain Behav Immun. 2011 Feb;25(2):221-9. Epub 2010 Oct 16
Manak M, Moshkoff M, Nguyen L, Meshki J, Tebas P, Tuluc F, and Douglas SDD. Anti-HIV Activity of the Neurokinin-1 Receptor Antagonist Aprepitant and Synergistic Interactions with other Antiretrovirals
AIDS. 2010 Nov 27;24(18):2789-96.
Douglas, S.D., Leeman, S.E. Neurokinin-1 Receptor: Functional Significance in the Immune System in Reference to Selected Infections and Inflammation. Ann N Y Acad Sci. 2010 Nov 22. doi: 10.1111/j.1749-
Vinet-Oliphant H, Alvarez X, Buza E, Borda J, Mohan M, Aye P, Tuluc F, Douglas SD, and Lackner A. Neurokinin-1 Receptor (NK1-R) Expression in the Brains of SIV-Infected Rhesus Macaques: Implications for Substance P in NK1-R Immune Cell Trafficking into the CNS. Am J. Pathol 2010 Sep;177(3):1286-97. Epub 2010 Jul 29.
Tuluc, F, Douglas, S.D., Lai, J.P., Kilpatrick, L.E.. : Neurokinin 1 receptor isoforms and the control of innate immunity. Trends Immunol. 2009 Jun;30(6):271-6. Epub 2009 May 7. 2009.
Douglas, S.D., Cnaan, A., Lynch, K.R., Benton, T., Zhao, H., Gettes, D.R., and Evans, D.L. Elevated Substance P Levels in HIV-Infected Women. Short Communication in AIDS Res. Human Retroviruses 24:3 375-378, 2008
Lai, JP, Lai, S, Tuluc, F, Tansky, MF, Kilpatrick, LE, Leeman, SE, Douglas, SD: Differences in the length of the carboxyl terminus mediate functional properties of neurokinin-1 receptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 105(34): 12605-12610, AUG 26 2008.
Evans, DL, Lynch, KG, Benton, T, Dube, B, Gettes, DR, Tustin, NB, Lai, JP, Metzger, D, Douglas, SD: Selective serotonin reuptake inhibitor and substance P antagonist enhancement of natural killer cell innate immunity in human immunodeficiency virus/acquired immunodeficiency syndrome. Biological Psychiatry 63(9): 899-905, MAY 1 2008.
Chernova, I., Lai, J-P, Li, H., Tuluc, F., Korchak, H.M., Douglas, S.D., and Kilpatrick, L.E. Substance P (SP) enhances CCL5-induced chemotaxis and intracellular signaling in human monocytes which express
the truncated neurokinin 1 receptor (NK1R). J Leukoc Biol 2009;85 154-164. PMCID: PMC2626768
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. USA 98:3970-3975, 2001.
- Professor of Microbiology at University of Pennsylvania School of Medicine (1980 – 1994)
- Professor of Pediatrics at University of Pennsylvania School of Medicine (1980– present)
- M.D., Immunology, Cornell University Medical College (1963)
- A.B., Cornell University (1959)