Humoral immunity is an essential component to clear infections and robust, long-lasting B cell-mediated memory is a correlate of protection for many vaccines. However, numerous factors related to both host and pathogen can influence the quality of humoral memory upon infection and vaccination. Studying the origin, maturation and evolutionary barriers of functionally active B cell clones provides valuable information on the natural history of effective and abherrant B cell reponses and a platform for the rational selection of immunogen designs.

The mission of the Translational Immunobiology Unit is to extend the basic understanding of B cell selection, clonal expansion and maturation into memory responses; to gather information from the natural evolution of B cell responses to inform effective immunogen designs, and to identify prophylactic and therapeutic antibody-based countermeasures. Studies will encompass primarily human and non-human primate specimens, as well as murine models, and will use multiple virus models, including HIV, flaviviruses, influenza virus, herpesviruses and betacoronaviruses.

Dr. Bonsignori received his M.D. and M.S. in clinical microbiology and virology from the University of Insubria Medical School in Varese, Italy. He conducted postdoctoral research in the Department of Immunology at St. Jude Children’s Research Hospital in Memphis, Tennessee before being appointed research associate at the Duke Human Vaccine Institute, Duke University School of Medicine in Durham, North Carolina, where his activity focused primarily on HIV vaccine development. In 2009, he established the Laboratory of B-cell Repertoire Analysis and ultimately attained the position of associate professor of medicine. In the HIV field, Dr. Bonsignori isolated multiple broadly neutralizing antibody B cell lineages from chronically HIV-1 infected individuals and characterized antibody/virus co-evolution to rationally select immunogen candidates for sequential vaccination schemes. Dr. Bonsignori developed a high-throughput memory B cell culture system for the functional screening of memory B cells at the single-cell level and conceptualized a novel framework for steering the immune response through immunogen design based on the probability of individual mutations and their effect on antibody effector functions. He later applied some of the technologies and workflows to study B cell responses to P. falciparum and Zika virus. Before NIAID, Dr. Bonsignori supported the Duke University student COVID-19 surveillance program by establishing a high-throughput workflow for the rapid accessioning, pooling and storage of nasal swab samples that sustained the screening of up to 20,000 samples per week.  Dr. Bonsignori joined the Laboratory of Infectious Diseases in March 2021.

SM, Zhang R, Montefiori DC, Henderson R, Nie X, Kelsoe G, Moody MA, Chen X, Joyce MG, Kwong PD, Connors M, Mascola JR, McGuire AT, Stamatatos L, Medina-Ramírez M, Sanders RW, Saunders KO, Kepler TB, Haynes BF. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity. 2018 Dec;49(6):1162-1174.e8.

Bonsignori M, Kreider EF, Fera D, Meyerhoff RR, Bradley T, Wiehe K, Alam SM, Aussedat B, Walkowicz WE, Hwang KK, Saunders KO, Zhang R, Gladden MA, Monroe A, Kumar A, Xia SM, Cooper M, Louder MK, McKee K, Bailer RT, Pier BW, Jette CA, Kelsoe G, Williams WB, Morris L, Kappes J, Wagh K, Kamanga G, Cohen MS, Hraber PT, Montefiori DC, Trama A, Liao HX, Kepler TB, Moody MA, Gao F, Danishefsky SJ, Mascola JR, Shaw GM, Hahn BH, Harrison SC, Korber BT, Haynes BF. Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies. Sci Transl Med. 2017 Mar;9(381):eaai7514.

Bonsignori M, Zhou T, Sheng Z, Chen L, Gao F, Joyce MG, Ozorowski G, Chuang GY, Schramm CA, Wiehe K, Alam SM, Bradley T, Gladden MA, Hwang KK, Iyengar S, Kumar A, Lu X, Luo K, Mangiapani MC, Parks RJ, Song H, Acharya P, Bailer RT, Cao A, Druz A, Georgiev IS, Kwon YD, Louder MK, Zhang B, Zheng A, Hill BJ, Kong R, Soto C; NISC Comparative Sequencing Program, Mullikin JC, Douek DC, Montefiori DC, Moody MA, Shaw GM, Hahn BH, Kelsoe G, Hraber PT, Korber BT, Boyd SD, Fire AZ, Kepler TB, Shapiro L, Ward AB, Mascola JR, Liao HX, Kwong PD, Haynes BF. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell. 2016 Apr;165(2):449-63.

Gao F, Bonsignori M, Liao HX, Kumar A, Xia SM, Lu X, Cai F, Hwang KK, Song H, Zhou T, Lynch RM, Alam SM, Moody MA, Ferrari G, Berrong M, Kelsoe G, Shaw GM, Hahn BH, Montefiori DC, Kamanga G, Cohen MS, Hraber P, Kwong PD, Korber BT, Mascola JR, Kepler TB, Haynes BF. Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies. Cell. 2014 Jul;158(3):481-91.

Bonsignori M, Wiehe K, Grimm SK, Lynch R, Yang G, Kozink DM, Perrin F, Cooper AJ, Hwang KK, Chen X, Liu M, McKee K, Parks RJ, Eudailey J, Wang M, Clowse M, Criscione-Schreiber LG, Moody MA, Ackerman ME, Boyd SD, Gao F, Kelsoe G, Verkoczy L, Tomaras GD, Liao HX, Kepler TB, Montefiori DC, Mascola JR, Haynes BF. An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1. J Clin Invest. 2014 Apr;124(4):1835-43.

Bonsignori M, Hwang KK, Chen X, Tsao CY, Morris L, Gray E, Marshall DJ, Crump JA, Kapiga SH, Sam NE, Sinangil F, Pancera M, Yongping Y, Zhang B, Zhu J, Kwong PD, O'Dell S, Mascola JR, Wu L, Nabel GJ, Phogat S, Seaman MS, Whitesides JF, Moody MA, Kelsoe G, Yang X, Sodroski J, Shaw GM, Montefiori DC, Kepler TB, Tomaras GD, Alam SM, Liao HX, Haynes BF. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J Virol. 2011 Oct;85(19):9998-10009.

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The Quantitative Virology and Evolution Unit focuses on understanding the dynamic and heterogenous processes of RNA virus infection and evolution. Using experimental tools, including high-resolution sequencing and live-cell microscopy, along with computational phylogenetic and bioinformatic tools, we characterize virus evolution and host-virus interactions across spatial and temporal scales. Projects in the lab include single-cell and single-genome sequencing of within-host virus evolution and host responses, phylogenetic reconstruction and evolutionary biochemistry in emerging RNA viruses, and design and analysis of mutational and functional genetic screens.

Patrick T. Dolan, Ph.D., is an experimental virologist and computational biologist whose work focuses primarily on the evolution and host-virus interactions of positive-sense RNA viruses. Patrick earned his B.S. degree in microbiology and molecular genetics from Michigan State University, where he worked in the laboratory of professor Yong-Hui Zheng on the antiviral function of APOBEC3 cytidine deaminases in HIV-1. Patrick earned his Ph.D. in biological sciences in 2014 from Purdue University, where he studied the form and function of the hepatitis C virus-host protein interaction network under the supervision of professor Douglas J. LaCount and co-advisor professor Michael Gribskov. Patrick then pursued postdoctoral studies at Stanford University and University of California, San Francisco, in the laboratories of professors Raul Andino and Judith Frydman where he developed methods to understand the evolutionary dynamics of enteroviruses and flaviviruses in alternative host environments. In the fall of 2021, Patrick began as unit chief of the Quantitative Virology and Evolution Unit at NIAID in Bethesda, MD, where he will continue to study the forces that shape the long- and short-term evolution of RNA virus populations. 

Dolan PT, Taguwa S, Rangel MA, Acevedo A, Hagai T, Andino R, Frydman J. Principles of dengue virus evolvability derived from genotype-fitness maps in human and mosquito cells. Elife. 2021 Jan;10:e61921. 

Dolan PT, Whitfield ZJ, Andino R. Mapping the Evolutionary Potential of RNA Viruses. Cell Host Microbe. 2018 Apr;23(4):435-446. 

Xiao Y, Dolan PT, Goldstein EF, Li M, Farkov M, Brodsky L, Andino R. Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses. Nat Commun. 2017 Aug;8(1):375. 

Dolan PT, Roth AP, Xue B, Sun R, Dunker AK, Uversky VN, LaCount DJ. Intrinsic disorder mediates hepatitis C virus core-host cell protein interactions. Protein Sci. 2015 Feb;24(2):221-35.

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The Transplant Infectious Diseases Consult Service is composed of experienced transplant infectious diseases physicians. In collaboration with the Blood and Immune Deficiency Cellular Therapy Program (BID-CTP), a clinical initiative that spans across four institutes within NIH, and with the Experimental Transplantation and Immunology Branch (ETIB), the consult service provides direct patient care, educational support and develops institutional guidelines for the prevention and management of infections for patients undergoing hematopoietic stem cell transplant, gene or cellular therapies at the NIH clinical center.

Dr. Cuellar Rodriguez received her medical degree from the Universidad Autónoma de Guadalajara (Guadalajara, Mexico) in 1999 and her Diploma in Tropical Medicine and Hygiene from the London School of Hygiene and Tropical Medicine (London, UK) in 2003. She completed an Internal Medicine residency and Infectious Diseases fellowship at the at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) in Mexico City, followed by a Clinical Fellowship in Transplant Infectious Diseases at the Cleveland Clinic in Cleveland, OH. In 2009, she joined NIAID as a clinical fellow (visiting program) where she completed an advanced infectious diseases fellowship (academic/research track) in infections in immunocompromised host. She was later promoted to staff clinician in 2011. In 2014, Dr. Cuellar Rodriguez returned to the INCMNSZ to serve as head of the Transplant Infectious Diseases Section, within the Department of Infectious Disease, where she remained until 2019. She then returned to NIAID in the Division of Intramural Research and is now the director of the Transplant Infectious Diseases Consult Service.

Juan Gea-Banacloche, M.D., Staff Clinician
Mark Parta, M.D., MPHTM, Physician III

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NIAID Infectious Diseases Fellowship Program