Dusan Bogunovic, PhD
- ASSISTANT PROFESSOR | Microbiology
- ASSISTANT PROFESSOR | Pediatrics
Research Topics:Cellular Immunity, Cytokines, Genetics, Genomics, Human Genetics and Genetic Disorders, Immune Deficiency, Immunology, Immunosuppression, Infectious Disease, Inflammation, Interferon, Lymphocytes, Viruses and Virology
Multi-Disciplinary Training AreaMicrobiology [MIC]
PhD, New York University Medical School, Sackler Institute
Postdoctoral Fellowship, The Rockefeller University
The Bogunovic lab focuses on the study of human immunogenetics. We aim to improve understanding of the human immune system by studying individuals with severe clinical presentations of infections usually causing mild or no clinical disease. To dissect these phenotypes we use genomic, genetic, molecular biology, cellular biology, immunology and clinical tools. The hypothesis of the lab is that inter-individual variability in susceptibility to infectious agents can also be explained by the immune genetic composition of the host. For example, we have recently identified null mutation in ISG15 in children who developed severe disease following an infection with usually innocuous strain of mycobacteria. As we discovered that lack of secreted ISG15 results in suboptimal production of interferon gamma, we are now interested in further dissecting the biology of secreted ISG15. Similarly, we are studying the pathogenesis of central nervous system infections with Listeria monocytogenes (neurolisteriosis), a foodborne pathogen. In immunocompetent individuals, infection with Listeria monocytogenes generally results in minor gastrointestinal problems. In rare cases, infection with Listeria monocytogenes may cause invasive infections, resulting in meningitis in this population, with significant mortality and morbidity. We aim to illuminate the elusive pathogenesis of these diseases, hoping to lay the foundation for a novel and paradigm-shifting approach to the rational design of both preventative medicine (vaccines and genetic counseling) and treatments beyond currently used antimicrobials.
Bogunovic D. Type I Interferons in Newborns-Neurotoxicity versus Antiviral Defense. mBio 2016 May; 7(3).
Speer SD, Li Z, Buta S, Payelle-Brogard B, Qian L, Vigant F, Rubino E, Gardner TJ, Wedeking T, Hermann M, Duehr J, Sanal O, Tezcan I, Mansouri N, Tabarsi P, Mansouri D, Francois-Newton V, Daussy CF, Rodriguez MR, Lenschow DJ, Freiberg AN, Tortorella D, Piehler J, Lee B, García-Sastre A, Pellegrini S, Bogunovic D. ISG15 deficiency and increased viral resistance in humans but not mice. Nature communications 2016 May; 7.
Zhang X, Bogunovic D, Payelle-Brogard B, Francois-Newton V, Speer SD, Yuan C, Volpi S, Li Z, Sanal O, Mansouri D, Tezcan I, Rice GI, Chen C, Mansouri N, Mahdaviani SA, Itan Y, Boisson B, Okada S, Zeng L, Wang X, Jiang H, Liu W, Han T, Liu D, Ma T, Wang B, Liu M, Liu JY, Wang QK, Yalnizoglu D, Radoshevich L, Uzé G, Gros P, Rozenberg F, Zhang SY, Jouanguy E, Bustamante J, García-Sastre A, Abel L, Lebon P, Notarangelo LD, Crow YJ, Boisson-Dupuis S, Casanova JL, Pellegrini S. Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation. Nature 2015 Jan; 517(7532).
Bogunovic D, Byun M, Durfee LA, Abhyankar A, Sanal O, Mansouri D, Salem S, Radovanovic I, Grant AV, Adimi P, Mansouri N, Okada S, Bryant VL, Kong XF, Kreins A, Velez MM, Boisson B, Khalilzadeh S, Ozcelik U, Darazam IA, Schoggins JW, Rice CM, Al-Muhsen S, Behr M, Vogt G, Puel A, Bustamante J, Gros P, Huibregtse JM, Abel L, Boisson-Dupuis S, Casanova JL. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science (New York, N.Y.) 2012 Sep; 337(6102).
Bogunovic D, Manches O, Godefroy E, Yewdall A, Gallois A, Salazar AM, Marie I, Levy DE, Bhardwaj N. TLR4 engagement during TLR3-induced proinflammatory signaling in dendritic cells promotes IL-10-mediated suppression of antitumor immunity. Cancer research 2011 Aug; 71(16).
Bogunovic D, O'Neill DW, Belitskaya-Levy I, Vacic V, Yu YL, Adams S, Darvishian F, Berman R, Shapiro R, Pavlick AC, Lonardi S, Zavadil J, Osman I, Bhardwaj N. Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival. Proceedings of the National Academy of Sciences of the United States of America 2009 Dec; 106(48).
Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, Abhyankar A, Israël L, Trevejo-Nunez G, Bogunovic D, Cepika AM, MacDuff D, Chrabieh M, Hubeau M, Bajolle F, Debré M, Mazzolari E, Vairo D, Agou F, Virgin HW, Bossuyt X, Rambaud C, Facchetti F, Bonnet D, Quartier P, Fournet JC, Pascual V, Chaussabel D, Notarangelo LD, Puel A, Israël A, Casanova JL, Picard C. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nature immunology 2012 Dec; 13(12).
Bogunovic D, Boisson-Dupuis S, Casanova JL. ISG15: leading a double life as a secreted molecule [review]. Experimental & molecular medicine 2013; 45.
Minkis K, Kavanagh DG, Alter G, Bogunovic D, O'Neill D, Adams S, Pavlick A, Walker BD, Brockman MA, Gandhi RT, Bhardwaj N. Type 2 Bias of T cells expanded from the blood of melanoma patients switched to type 1 by IL-12p70 mRNA-transfected dendritic cells. Cancer research 2008 Nov; 68(22).
Kong XF, Ciancanelli M, Al-Hajjar S, Alsina L, Zumwalt T, Bustamante J, Feinberg J, Audry M, Prando C, Bryant V, Kreins A, Bogunovic D, Halwani R, Zhang XX, Abel L, Chaussabel D, Al-Muhsen S, Casanova JL, Boisson-Dupuis S. A novel form of human STAT1 deficiency impairing early but not late responses to interferons. Blood 2010 Dec; 116(26).
Feig JE, Pineda-Torra I, Sanson M, Bradley MN, Vengrenyuk Y, Bogunovic D, Gautier EL, Rubinstein D, Hong C, Liu J, Wu C, van Rooijen N, Bhardwaj N, Garabedian M, Tontonoz P, Fisher EA. LXR promotes the maximal egress of monocyte-derived cells from mouse aortic plaques during atherosclerosis regression. The Journal of clinical investigation 2010 Dec; 120(12).
Segura MF, Hanniford D, Menendez S, Reavie L, Zou X, Alvarez-Diaz S, Zakrzewski J, Blochin E, Rose A, Bogunovic D, Polsky D, Wei J, Lee P, Belitskaya-Levy I, Bhardwaj N, Osman I, Hernando E. Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proceedings of the National Academy of Sciences of the United States of America 2009 Feb; 106(6).
Kong XF, Vogt G, Itan Y, Macura-Biegun A, Szaflarska A, Kowalczyk D, Chapgier A, Abhyankar A, Furthner D, Djambas Khayat C, Okada S, Bryant VL, Bogunovic D, Kreins A, Moncada-Vélez M, Migaud M, Al-Ajaji S, Al-Muhsen S, Holland SM, Abel L, Picard C, Chaussabel D, Bustamante J, Casanova JL, Boisson-Dupuis S. Haploinsufficiency at the human IFNGR2 locus contributes to mycobacterial disease. Human molecular genetics 2013 Feb; 22(4).
Ott PA, Henry T, Baranda SJ, Frleta D, Manches O, Bogunovic D, Bhardwaj N. Inhibition of both BRAF and MEK in BRAF(V600E) mutant melanoma restores compromised dendritic cell (DC) function while having differential direct effects on DC properties. Cancer immunology, immunotherapy : CII 2013 Apr; 62(4).