Biosketch / Results /

Michael Weiden

Associate Professor, Department of Medicine
Associate Professor, Department of Environmental Medicine

Assist Pog Dir (Genomics) GCRC

Contact Info

Address
462 First Avenue
New York, NY 10016

212/263-6479
Michael.Weiden@nyumc.org

Education

— Resident, Internal Medicine, Presbyterian Hospital, New York (1985-87), Residency Training
— Fellow, Pulmonary and Critical Care, Presbyterian Hospital, New York, NY (1987-90), Clinical Fellowships
— SUNY Stony Brook, New York (1984), Medical Education
— Intern, Internal Medicine, Presbyterian Hospital, New York (1984-85), Internship

Research Summary

We have investigated the mechanism for the deterioration in immune status produced by tuberculosis in AIDS patients. We have observed that tuberculosis accelerates AIDS by enhancing viral replication and mutation in the lung. Tuberculosis also alters chemokine co-receptor expression on macrophages creating a permissive environment for production of pathogenic viral phenotypes. In the absence of inflammation, alveolar macrophages do not support HIV-1 replication. This suggests that without pneumonia, cellular factors actively inhibit viral replication in the lung. We searched for transcription factors that repress the HIV-1 LTR promoter in the absence of inflammation and found that alveolar macrophages normally express dominant negative transcription factors that represses the HIV-1 LTR. Production of these transcriptional repressors is a novel interferon response. Monocytes are unable to produce the repressors and so investigation of blood monocytes did not reveal this pathway that controls HIV-1 replication in the lung. Differentiation of monocytes to macrophages is required for production of the transcriptional repressors and antiviral effect of interferon or IL-10. During tuberculosis, expression of this repressor is lost. Lymphocyte/macrophage or PMN/macrophage contact is required for loss of the dominate-negative transcription factors. Signaling through both CD40 and CD80/86 is required for de-repression; this in combination proinflammatory cytokines or reactive oxygen intermediates are necessary and sufficient for the high level of HIV-1 replication observed during tuberculosis. De-repression of macrophages mediated through co-stimulatory molecule signaling is a novel mechanism of immune activation leading to enhanced HIV replication in the innate and cellular immune response.

Research Interests

Lung infection and inflammation

Lung Function Trajectories in World Trade Center-Exposed New York City Firefighters Over 13 Years: The Roles of Smoking and Smoking Cessation
Aldrich, Thomas K; Vossbrinck, Madeline; Zeig-Owens, Rachel; Hall, Charles B; Schwartz, Theresa M; Moir, William; Webber, Mayris P; Cohen, Hillel W; Nolan, Anna; Weiden, Michael D; Christodoulou, Vasilios; Kelly, Kerry J; Prezant, David J. Lung Function Trajectories in World Trade Center-Exposed New York City Firefighters Over 13 Years: The Roles of Smoking and Smoking Cessation. Chest. 2016 Jun;149(6):1419-1427 (2143002)

Radiologic Features of World Trade Center-related Sarcoidosis in Exposed NYC Fire Department Rescue Workers
Girvin, Francis; Zeig-Owens, Rachel; Gupta, Deepti; Schwartz, Theresa; Liu, Yang; Weiden, Michael D; Prezant, David J; Naidich, David P. Radiologic Features of World Trade Center-related Sarcoidosis in Exposed NYC Fire Department Rescue Workers. Journal of thoracic imaging. 2016 Sep ;31(5):296-303 (2185572)

Blood Eosinophils and World Trade Center Exposure Predict Surgery in Chronic Rhinosinusitis: A 13.5-Year Longitudinal Study
Kwon, Sophia; Putman, Barbara; Weakley, Jessica; Hall, Charles B; Zeig-Owens, Rachel; Schwartz, Theresa; Olivieri, Brianne; Singh, Ankura; Huie, Maryann; Morrison, Debra; Webber, Mayris P; Cohen, Hillel W; Kelly, Kerry J; Aldrich, Thomas K; Nolan, Anna; Prezant, David J; Shohet, Michael R; Weiden, Michael D. Blood Eosinophils and World Trade Center Exposure Predict Surgery in Chronic Rhinosinusitis: A 13.5-Year Longitudinal Study. Annals of the American Thoracic Society. 2016 Aug ;13(8):1253-1261 (2080052)

Blood Eosinophils and World Trade Center Exposure Predict Surgery in Chronic Rhinosinusitis: A 13.5-Year Longitudinal Study
Kwon, Sophia; Putman, Barbara; Weakley, Jessica; Hall, Charles B; Zeig-Owens, Rachel; Schwartz, Theresa; Webber, Mayris P; Cohen, Hillel W; Aldrich, Thomas K; Prezant, David; Nolan, Anna; Weiden, Michael D. Blood Eosinophils and World Trade Center Exposure Predict Surgery in Chronic Rhinosinusitis: A 13.5-Year Longitudinal Study [Meeting Abstract]. American journal of respiratory & critical care medicine. 2016 ;193(Online Abstracts):?-? #A5443 (2097712)

Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype
Segal, Leopoldo N; Clemente, Jose C; Tsay, Jun-Chieh J; Koralov, Sergei B; Keller, Brian C; Wu, Benjamin G; Li, Yonghua; Shen, Nan; Ghedin, Elodie; Morris, Alison; Diaz, Phillip; Huang, Laurence; Wikoff, William R; Ubeda, Carles; Artacho, Alejandro; Rom, William N; Sterman, Daniel H; Collman, Ronald G; Blaser, Martin J; Weiden, Michael D. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nature microbiology. 2016 ;1:16031-16031 (2231952)