NIH VideoCast - Law of STAT fives, root orchestrators of lymphocyte homeostasis and function

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Law of STAT fives, root orchestrators of lymphocyte homeostasis and function

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Air date:	Wednesday, June 28, 2017, 4:15:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 360 (38 Live, 322 On-demand)
Category:	Immunology
Runtime:	01:07:33
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	Immunology Interest Group Seminar Series The transcription factor STAT5 is fundamental to the mammalian immune system. Operating downstream of cytokines and growth factors, it impacts all aspects of lymphocyte biology, from general cellular processes like proliferation and apoptosis, to specialized immunological programs like effector and regulatory T cell differentiation. Genetic studies in humans underscore its widespread influence as mutations of STAT5 or upstream activators manifest varied Alejandro Villarino, NIAMS, NIHimmunological phenotypes including immunodeficiency, autoimmunity and hematological malignancies. Mouse models of STAT5 deficiency have affirmed these findings and have been instrumental in defining its broad homeostatic and metabolic functions, as well as lineage-restricted pro- and anti-inflammatory capabilities. Coupled to high-throughput sequencing technologies, they have also enabled genome-wide discovery of STAT5-dependent gene networks in both innate and adaptive lymphocytes, and have yielded valuable mechanistic insights on how it instructs gene transcription. Ongoing research will further clarify how STAT5 works at cellular, molecular and genomic levels with the overarching goal of informing the development of therapeutic agents to target STAT5 and/or relevant downstream targets. Alejandro Villarino is a post-doctoral research fellow in the laboratory of John O’Shea in NIAMS. His interest in cytokines began as a graduate student in Chris Hunter’s laboratory at the University of Pennsylvania when he first encountered the double-edged nature of infection-induced cytokine responses. That dichotomy was the theme of his dissertation on interleukin-27, a cytokine that was initially classified as pro-inflammatory but which he discovered has critical anti-inflammatory properties that have since been observed in numerous disease settings. Following a string of highly cited publications, he transitioned to postdoctoral research in Abul Abbas’ lab at the University of California San Francisco where he studied cell intrinsic mechanisms regulating lymphocyte cytokine production in the context of autoimmune disease. This was also a prolific period, both in terms of scientific growth and publication output, that afforded him the opportunity to mentor several junior lab members, among them a research assistant whose work culminated in a peer reviewed article where he is credited as senior author. Since joining the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Alejandro have embraced next-generation sequencing as a means of interrogating cytokine signaling. His work here has focused on cytokines operating via STAT5, a central transcription factor in lymphocyte biology and increasingly relevant drug target for autoimmune and metastatic disease. Using a combination of genetic and genomic approaches, he has addressed the long-standing question of whether STAT5A and STAT5B, the two mammalian STAT5 paralogs, are redundant or functionally distinct. He has also defined cellular and molecular functions for STAT5 across innate and adaptive lymphocyte lineages, identified important STAT5-containing transcription factor networks, and uncovered a key role for STAT5 in metabolic programming of immune cells. This work has yielded valuable insights on how STAT5 impacts lymphocyte biology, many of which are relevant for other STATs and transcription factors, and has empowered him with the skill sets necessary to design, execute and analyze genome- and transcriptome-level experiments involving small numbers of primary immune cells and multiple variables (i.e. different genotypes, cell populations, cytokine treatments).

NLM Title:	Law of STAT fives, root orchestrators of lymphocyte homeostasis and function / Alejandro Villarino.
Author:	Villarino, Alejandro. National Institutes of Health (U.S.),
Publisher:
Abstract:	(CIT): Immunology Interest Group Seminar Series The transcription factor STAT5 is fundamental to the mammalian immune system. Operating downstream of cytokines and growth factors, it impacts all aspects of lymphocyte biology, from general cellular processes like proliferation and apoptosis, to specialized immunological programs like effector and regulatory T cell differentiation. Genetic studies in humans underscore its widespread influence as mutations of STAT5 or upstream activators manifest varied Alejandro Villarino, NIAMS, NIHimmunological phenotypes including immunodeficiency, autoimmunity and hematological malignancies. Mouse models of STAT5 deficiency have affirmed these findings and have been instrumental in defining its broad homeostatic and metabolic functions, as well as lineage-restricted pro- and anti-inflammatory capabilities. Coupled to high-throughput sequencing technologies, they have also enabled genome-wide discovery of STAT5-dependent gene networks in both innate and adaptive lymphocytes, and have yielded valuable mechanistic insights on how it instructs gene transcription. Ongoing research will further clarify how STAT5 works at cellular, molecular and genomic levels with the overarching goal of informing the development of therapeutic agents to target STAT5 and/or relevant downstream targets. Alejandro Villarino is a post-doctoral research fellow in the laboratory of John O"Shea in NIAMS. His interest in cytokines began as a graduate student in Chris Hunter"s laboratory at the University of Pennsylvania when he first encountered the double-edged nature of infection-induced cytokine responses. That dichotomy was the theme of his dissertation on interleukin-27, a cytokine that was initially classified as pro-inflammatory but which he discovered has critical anti-inflammatory properties that have since been observed in numerous disease settings. Following a string of highly cited publications, he transitioned to postdoctoral research in Abul Abbas" lab at the University of California San Francisco where he studied cell intrinsic mechanisms regulating lymphocyte cytokine production in the context of autoimmune disease. This was also a prolific period, both in terms of scientific growth and publication output, that afforded him the opportunity to mentor several junior lab members, among them a research assistant whose work culminated in a peer reviewed article where he is credited as senior author. Since joining the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Alejandro have embraced next-generation sequencing as a means of interrogating cytokine signaling. His work here has focused on cytokines operating via STAT5, a central transcription factor in lymphocyte biology and increasingly relevant drug target for autoimmune and metastatic disease. Using a combination of genetic and genomic approaches, he has addressed the long-standing question of whether STAT5A and STAT5B, the two mammalian STAT5 paralogs, are redundant or functionally distinct. He has also defined cellular and molecular functions for STAT5 across innate and adaptive lymphocyte lineages, identified important STAT5-containing transcription factor networks, and uncovered a key role for STAT5 in metabolic programming of immune cells. This work has yielded valuable insights on how STAT5 impacts lymphocyte biology, many of which are relevant for other STATs and transcription factors, and has empowered him with the skill sets necessary to design, execute and analyze genome- and transcriptome-level experiments involving small numbers of primary immune cells and multiple variables (i.e. different genotypes, cell populations, cytokine treatments).
Subjects:	Adaptive Immunity Homeostasis--immunology Immunity, Innate Lymphocytes--immunology STAT5 Transcription Factor--deficiency STAT5 Transcription Factor--immunology
Publication Types:	Lecture Webcast

NLM Classification:	QW 568
NLM ID:	101710189
CIT Live ID:	18604
Permanent link:	https://videocast.nih.gov/watch=18604

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