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Michael D. Weiden

Michael D. Weiden, MD

Professor, Department of Medicine

lung infection and inflammation

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.

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Assistant Program Director (Genomics) GCRC

MD from State University of New York at Stony Brook

Goldfarb, David G; Hall, Charles B; Choi, Jaeun; Zeig-Owens, Rachel; Cohen, Hillel W; Cannon, Madeline; Prezant, David J; Weiden, Michael D

Annals of the American Thoracic Society. 2023 Aug; 20(8):1136-1143

Ferastraoaru, Denisa; Zeig-Owens, Rachel; Goldfarb, David G; Mueller, Alexandra K; Hall, Charles B; Weiden, Michael D; Schwartz, Theresa; Prezant, David J; Rosenstreich, David

Annals of allergy, asthma & immunology. 2022 Dec; 129(6):769-775

Jasra, Sakshi; Giricz, Orsi; Zeig-Owens, Rachel; Pradhan, Kith; Goldfarb, David G; Barreto-Galvez, Angelica; Silver, Alexander J; Chen, Jiahao; Sahu, Srabani; Gordon-Mitchell, Shanisha; Choudhary, Gaurav S; Aluri, Srinivas; Bhagat, Tushar D; Shastri, Aditi; Bejan, Cosmin A; Stockton, Shannon S; Spaulding, Travis P; Thiruthuvanathan, Victor; Goto, Hiroki; Gerhardt, Jeannine; Haider, Syed Hissam; Veerappan, Arul; Bartenstein, Matthias; Nwankwo, George; Landgren, Ola; Weiden, Michael D; Lekostaj, Jacqueline; Bender, Ryan; Fletcher, Frederick; Greenberger, Lee; Ebert, Benjamin L; Steidl, Ulrich; Will, Britta; Nolan, Anna; Madireddy, Advaitha; Savona, Michael R; Prezant, David J; Verma, Amit

Nature medicine. 2022 Mar; 28(3):468-471

Cleven, Krystal L; Rosenzvit, Carla; Nolan, Anna; Zeig-Owens, Rachel; Kwon, Sophia; Weiden, Michael D; Skerker, Molly; Halpren, Allison; Prezant, David J

Lung. 2021 Dec; 199(6):569-578

Goldfarb, David G; Putman, Barbara; Lahousse, Lies; Zeig-Owens, Rachel; Vaeth, Brandon M; Schwartz, Theresa; Hall, Charles B; Prezant, David J; Weiden, Michael D

American journal of industrial medicine. 2021 Oct; 64(10):853-860

Weiden, Michael D; Singh, Ankura; Goldfarb, David G; Putman, Barbara; Zeig-Owens, Rachel; Schwartz, Theresa; Cohen, Hillel W; Prezant, David J

American journal of industrial medicine. 2021 Oct; 64(10):845-852

Sulaiman, Imran; Chung, Matthew; Angel, Luis; Tsay, Jun-Chieh J; Wu, Benjamin G; Yeung, Stephen T; Krolikowski, Kelsey; Li, Yonghua; Duerr, Ralf; Schluger, Rosemary; Thannickal, Sara A; Koide, Akiko; Rafeq, Samaan; Barnett, Clea; Postelnicu, Radu; Wang, Chang; Banakis, Stephanie; Pérez-Pérez, Lizzette; Shen, Guomiao; Jour, George; Meyn, Peter; Carpenito, Joseph; Liu, Xiuxiu; Ji, Kun; Collazo, Destiny; Labarbiera, Anthony; Amoroso, Nancy; Brosnahan, Shari; Mukherjee, Vikramjit; Kaufman, David; Bakker, Jan; Lubinsky, Anthony; Pradhan, Deepak; Sterman, Daniel H; Weiden, Michael; Heguy, Adriana; Evans, Laura; Uyeki, Timothy M; Clemente, Jose C; de Wit, Emmie; Schmidt, Ann Marie; Shopsin, Bo; Desvignes, Ludovic; Wang, Chan; Li, Huilin; Zhang, Bin; Forst, Christian V; Koide, Shohei; Stapleford, Kenneth A; Khanna, Kamal M; Ghedin, Elodie; Segal, Leopoldo N

Nature microbiology. 2021 Oct; 6(10):1245-1258

Sulaiman, Imran; Wu, Benjamin G; Li, Yonghua; Tsay, Jun-Chieh; Sauthoff, Maya; Scott, Adrienne S; Ji, Kun; Koralov, Sergei B; Weiden, Michael; Clemente, Jose; Jones, Drew; Huang, Yvonne J; Stringer, Kathleen A; Zhang, Lingdi; Geber, Adam; Banakis, Stephanie; Tipton, Laura; Ghedin, Elodie; Segal, Leopoldo N

European respiratory journal. 2021 Jul; 58(1):