Dr. Steven D. Douglas has been investigating cellular immune mechanisms and monocyte-macrophages over many years. He and his group investigate the interaction between neuropeptides, monocyte-macrophages and HIV.
Dr. Douglas is the principal investigator for the Philadelphia International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Unit, which includes a clinical research Site at The Children's Hospital of Philadelphia, the Adult Unit at the Hospital of the University of Pennsylvania, the Hospital of the University of Pennsylvania and Pennsylvania Hospital.
Dr. Douglas’ laboratory is the central immunology laboratory for the IMPAACT Network, and a specialty immunology laboratory. He is the principal investigator for the Adolescent Trial Network. These networks are state-of-the-art therapeutic trials for adult and pediatric HIV/AIDS throughout the world. Dr. Douglas' ongoing program involves molecular and cellular immunologic studies of substance P in monocyte-macrophages. His laboratory has discovered the truncated from of NK1-R and demonstrated that SP antagonists block HIV through CCR5 and applied as novel HIV therapy. He has also demonstrated up-regulation of substance P by HIV.
In addition, 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 as a mitogen that stimulates lymphocytes 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 of the Society for Leukocyte Biology. He has chaired committees for the VA, FDA (Blood Products Advisory Committee) and chairs the NIH-CSR (AIDS Immunology Pathogenesis Study Section).
He was 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 of ASCI, American Academy Microbiology, Honorary Life Member Society for Leukocyte Biology, Fellow AAAS.
Dr. Douglas is developing new HIV-l therapies that utilize novel antiviral mechanisms, exert a positive immunomodulatory effect and have positive behavioral effects.
MD - Cornell University Medical College, Ithaca, NY
Medicine - Mt. Sinai School of Medicine, New York, NY
Immunology - University of California, San Francisco, San Francisco, CA
Medical Laboratory Immunology
Medical Director, Immunogenetics Laboratory
Associate Chair, Academic Affairs, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania
Interaction between immune system and stress
Alcohol and HIV
Neurokinin-1R (SP Receptor) Antagonists for HIV Therapy
Vinet-Oliphant H, Alvarez X, Buza E, Borda JT, Mohan M, Aye PP, Tuluc F, Douglas SD, Lackner AA. 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 Jul 29. [Epub ahead of print]. Read abstract
Campbell DE, Lai JP, Tustin NB, Riedel E, Tustin R 3rd, Taylor J, Murray J, Douglas SD. Analytical and biological considerations in the measurement of cell-associated CCR5 and CXCR4 mRNA and protein. Clin Vaccine Immunol. 2010 Jul;17(7):1148-54. Epub 2010 May 12. Read abstract
Meshki J, Douglas SD, Lai JP, Schwartz L, Kilpatrick LE, Tuluc F. Neurokinin 1 receptor (NK1R) mediates membrane blebbing in HEK293 cells through a Rho/ROCK-dependent mechanism. J Biol Chem. 2009;Apr 3;284(14):9280-9
Douglas SD, Lai JP, Tuluc F, Kilpatrick LE. Neurokinin 1 receptor isoforms and the control of innate immunity. Trends Immunol. 2009 Jun;30(6):271-6. Epub 2009 May 7. 2009
Chernova I, Lai J-P, Li H, Tuluc F, Korchak HM, Douglas SD, Kilpatrick LE. Substance P (SP) enhances CCL5-induced chemotaxis and intracellular signaling in human monocytes which express the truncated neurokinin 1 receptor (NK1R). J Leukoc Biol. 2008;85 154-164
Douglas SD, Lai J-P, Tuluc F, Schwartz L, Kilpatrick LE. Neurokinin-1 Receptor Expression and Function in Human Macrophages and Brain - Role in HIV Neuropathogenesis - (Perspective. Ann N Y Acad Sci. 2008;1144:90-6
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. 2008 Aug 26;105(34):12605-12610.
Lai JP, Ho WZ, Kilpatrick LE, Wang X, Tuluc F, Korchak HM, Douglas SD. Full-length and truncated neurokinin-1 receptor expression and function during monocyte/macrophage differentiation. Proceedings Of The National Academy Of Sciences Of The United States Of America. 2006 May 16;103(20):7771-7776.