- ASSOCIATE PROFESSOR Genetics and Genomic Sciences
- Antigen Presentation
- Cell Biology
- Cellular Immunity
- Dendritic Cells
- Gene Discovery
- Gene Expressions
- Gene Regulation
- Gene Therapy
- Immunological Tolerance
- Infectious Disease
- Molecular Biology
- RNA Splicing & Processing
- T Cells
- Transcriptional Activation and Repression
- Transgenic Mice
- Dr. Brian Brown was featured in Inside Mount Sinai. He was recently awarded the Diabetes Pathfinder Award, a new, five-year federal grant that supports creative new investigators who present innovative research projects focused on type 1 diabetes.
For a number of years, Dr. Brian Brown has been active developing strategies for promoting immunological tolerance. His involvement began with his doctoral studies in Canada and his work with virologist Dr. Frank Graham and hematologist Dr. David Lillicrap to establish ways to overcome the immune response hindering hemophilia gene therapy. He subsequently did his postdoctoral studies in Italy under the supervision of Drs. Luigi Naldini and Maria Grazia Roncarolo, leaders in molecular medicine and immunology. There, he helped develop a new platform for controlling gene expression, which has led to improvements in experimental treatments for hemophilia, cancer, and viral infection. Now, Dr. Brown and his laboratory are applying this strategy to develop ways to prevent type I diabetes.
Visit the Brown Lab homepage at:
ResearchSpecific Clinical/Research Interests:
Immunology; Immunological Tolerance; Infectious Disease; Inflammation; Antigen Presentation; Dendritic Cells; Autoimmunity; Diabetes; Molecular Biology; Gene Discovery; Gene Expressions; Gene Regulation; RNA; RNA Regulation; microRNA; Regulation of the Innate Immune System
Summary of Research Studies:
We are studying the role of microRNA regulation in antigen presenting cells of the innate immune system. microRNA are a class of small non-coding RNAs, which play a major role in regulating gene expression. Little is known about the role of microRNAs in antigen presenting cells. Through the use of novel technologies we are investigating how microRNAs influence the development and function of dendritic cells, macrophages, and other APCs. Questions we are trying to address include, understanding how microRNAs influence the response of these cells to external stimuli, such as viral and bacterial components, and disease conditions, and how microRNAs regulate the antigen presenting capacity of these cells.
Autoimmune diseases, such as type I diabetes and multiple sclerosis, affect more then 23 million Americans, and are one of the leading causes of death in children. Our laboratory is developing ways to prevent autoimmune disease by studying ways to induce antigen-specific immunological tolerance. To do this we are employing a novel approach to target antigens to tolerogenic cell types by exploiting the microRNA regulatory network of these cells. This targeting strategy will help us to identify cell types and cell states that can direct T cells to become regulatory T cells. We will also apply this approach to prevent the development of type I diabetes in a diabetes-prone mouse model.
Postdoctoral and graduate projects are available involving: (i) the study of microRNA regulation in antigen presenting cells, (ii) the discovery of novel gene expression networks, in the immune system and (iii) the development of strategies to prevent type I diabetes.
Israelow B, Mullokandov G, Agudo J, Sourisseau M, Bashir A, Maldonado AY, Dar AC, Brown BD, Evans MJ. Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors. Nature communications 2014; 5.
Agudo J, Ruzo A, Tung N, Salmon H, Leboeuf M, Hashimoto D, Becker C, Garrett-Sinha LA, Baccarini A, Merad M, Brown BD. The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids. Nature Immunology 2013 Nov;.
Miller JC, Brown BD, Shay T, Gautier EL, Jojic V, Cohain A, Pandey G, Leboeuf M, Elpek KG, Helft J, Hashimoto D, Chow A, Price J, Greter M, Bogunovic M, Bellemare-Pelletier A, Frenette PS, Randolph GJ, Turley SJ, Merad M. Deciphering the transcriptional network of the dendritic cell lineage. Nature Immunology 2012 Sep; 13(9).
Mullokandov G, Baccarini A, Ruzo A, Jayaprakash AD, Tung N, Israelow B, Evans MJ, Sachidanandam R, Brown BD. High-throughput assessment of microRNA activity and function using microRNA sensor and decoy libraries. Nature Methods 2012 Aug; 9(8).
Baccarini A, Chauhan H, Gardner TJ, Jayaprakash AD, Sachidanandam R, Brown BD. Kinetic analysis reveals the fate of a microRNA following target regulation in mammalian cells. Current Biology 2011 Mar; 21(5).
Chow A, Brown BD, Merad M. Studying the mononuclear phagocyte system in the molecular age. Nature Reviews Immunology 2011 Nov; 11(11).
Brown BD, Naldini L. Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nature Reviews Genetics 2009 Aug; 10(8).
Gentner B, Schira G, Giustacchini A, Amendola M, Brown BD, Ponzoni M, Naldini L. Stable knockdown of microRNA in vivo by lentiviral vectors. Nature Methods 2009 Jan; 6(1): 63-66.
Brown BD, Gentner B, Cantore A, Colleoni S, Amendola M, Zingale A, Baccarini A, Lazzari G, Galli C, Naldini L. Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state. Nature Biotechnology 2007 Dec; 25(12): 1457-1467.
Brown BD, Cantore A, Annoni A, Sergi LS, Lombardo A, Della Valle P, D'Angelo A, Naldini L, Galli C, Naldini L. A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice. Blood 2007 Aug; 110(13): 4144-4152.
Brown BD, Sitia G, Annoni A, Hauben E, Sergi LS, Zingale A, Roncarolo MG, Guidotti L, Naldini L. In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance. Blood 2007 April; 109(7): 2797-2805.
Brown BD, Venneri MA, Zingale A, Sergi Sergi L, Naldini L. Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer. Nature Medicine 2006 May; 12(5): 585-591.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Brown did not report having any of the following types of financial relationships with industry during 2014 and/or 2015: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
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