Heads of Laboratories
Laurie and Peter Grauer Assistant Professor
Laboratory of Lymphocyte Dynamics
Victora studies germinal centers, structures within lymphoid organs where antibodies mutate and improve their targeting capabilities. This process, called affinity maturation, allows the immune system to produce antibodies that are precisely targeted at invaders, resulting in faster and more robust responses upon subsequent exposures.
When a pathogen invades the human body, the immune system responds by producing proteins called antibodies that are precisely targeted at the invader. Antibody production creates an immunological memory that allows for a faster and more robust response to the invader upon subsequent exposures. It is also the basis for vaccination.
Antibodies are tuned to efficiently recognize a specific invader through affinity maturation, in which a small region of the antibody undergoes random hypermutation followed by the proliferation of mutants with high affinity to the pathogen. This process occurs in anatomical structures within lymphoid organs known as germinal centers (GCs), where B cells—the cells that produce antibodies—multiply and mutate. The Victora lab is currently investigating the mechanistic details of this process. His research could lead to more effective vaccines against pathogens such as influenza or HIV, and could help explain how affinity maturation can malfunction in diseases such as allergies.
In previous work, Victora developed techniques to label and observe cells within the lymph nodes of live mice, and was able to shed light on how B cells with high-affinity antibodies are selected and amplified. In addition to defining the types of B cells in GCs and their migration patterns, the research identified another major component of the immune system, T cells, as the regulators of this process. His work also showed that, unlike B cells, T cells are not physically restricted to individual GCs and can help maintain diversity in the antibody response.
To gain a deeper understanding of how high-affinity antibodies are generated and evolve during this complex process, the Victora lab is now exploring three complementary perspectives: those of molecules, cells, and whole organs. On the molecular scale, research is underway to identify the key genes involved in how B cells choose between two fates—to remain within the GC or to differentiate into another cell type. At the cellular level, the lab is exploring how a cell’s history of interactions with other cells contributes to affinity maturation and GC development. Finally, Victora and colleagues are investigating how different GCs within the same lymphoid organ may vary in terms of the antibodies they carry, and how these antibodies change over time to produce an effective antibody response.
By applying a broad scope in their work—from individual genes to the dynamics within the spleen and lymph nodes—the Victora lab hopes to gain insight into the critical evolutionary processes by which the immune system refines its response to an infection or vaccine.
B.M. in piano, 1998
M.M. in piano, 2000
Mannes College of Music
M.Sci. in immunology, 2006
University of São Paulo
Ph.D. in immunology, 2011
New York University
Whitehead Fellow, 2012–2016
Whitehead Institute for Biomedical Research
Assistant Professor, 2016–
The Rockefeller University
NIH Director’s Early Independence Award, 2012
SciLifeLab Prize for Young Scientists, 2013
Searle Scholar, 2017
MacArthur Fellowship, 2017
Pasqual, G. et al. Monitoring T cell-dendritic cell interactions in vivo by intercellular enzymatic labelling. Nature 553, 496–500 (2018).
Ersching, J. et al. Germinal center selection and affinity maturation require dynamic regulation of mTORC1 kinase. Immunity 46, 1045–1058 (2017).
Tas, J.M. et al. Visualizing antibody affinity maturation in germinal centers. Science 351, 1048–1054 (2016).
Shulman, Z. et al. T follicular helper cell dynamics in germinal centers. Science 341, 673–677 (2013).
Victora G.D. et al. Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143, 592–605 (2010).