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K. Mark Ansel
The laboratory's major research focus is regulation of gene expression in lymphocytes, and how changes in gene expression are orchestrated to confer new functions and cellular identities on these cells during their differentiation. We are particularly interested in the role of regulatory RNA and control of regulatory RNA expression.
Other Research in Dr. Ansel's lab:
Allergy and Asthma • Immune Regulation
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Jason Cyster
The Cyster lab studies the role of chemokines in lymphoid organ development, the differentiation events involved in Germinal Center formation and the factors involved in follicular dendritic cell (FDC) maturation and dendritic cell homeostasis.
Other Research in Dr. Cyster's Lab
Diabetes and Autoimmunity • Immune Regulation • Immune Receptors and Signaling • Immune Response to Microbial Pathogenesis
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Nigel Killeen
A major focus in the lab is the generation and use of novel genetic systems to mutate and/or mark lymphocytes as they experience specific signals, so that the fate of the cells can then be followed, and the impact of any induced mutation understood. One example of this has been our recent use of an Ox40-cre allele to mark and mutate T cells during immune responses. With Ox40-cre we have discriminated populations of memory T cells that differ from one another phenotypically and we can correlate these differences with disparate signaling experiences. We are interested in exploiting Ox40-cre and other new genetic marking systems to understand more about the mechanisms that govern the formation of different kinds of effector and memory T cells with a view to developing better approaches for treating disease with vaccines.
As part of our interest in T cell development and lineage commitment, we have also been studying specific cell surface molecules whose functions impinge on key signaling processes in particular the signaling that derives from the T cell antigen receptor. These molecules include CD5, CD6, CD166, and the Tumor Necrosis Receptor Family member known as OX40. We have identified selective roles for each of these molecules in various aspects of T cell development and immune responses, and we are continuing to determine how immune responses are made more fit because of these roles.
Other Research in Dr. Killeen's lab:
Allergy and Asthma, Diabetes and Autoimmunity, HIV and Viral Immunity, Immune Regulation, Immune Receptors and Signaling, Immune Response to Microbial Pathogens
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Richard Locksley
The laboratory uses murine models of helminth infection and allergic lung disease in various genetically modified animals to examine interactions between innate and adaptive immune cells that together mediate immunity nucleated by Th2 cells. The laboratory is closely aligned with the Sandler Basic Asthma Research Center at UCSF, with core support facilities including murine models of allergic pulmonary injury, microarray capabilities and multichannel sorting and analytic instruments.
Other Research in Dr. Locksley's lab:
Imune Regulation • Immune Response to Microbial Pathogens •
Inflammation
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Michael McManus
The McManus lab studies biological processes relating to RNA interference pathways, using the mouse as a model. This includes the study of small (18-26 nucleotide) regulatory RNAs of biological significance, such as microRNAs, and the genetic factors involved in small RNA genesis.
In the past few years several groups have published the sequences for over 1000 microRNAs from plants to humans and this number is growing. In fact, approximately 1% of all known human genes encode microRNAs, yet we know very little about their function. Our lab is interested in understanding how microRNAs contribute to the specification of cell fate, and how disregulation of microRNAs may contribute to human disease.
We have generated a mouse knockout for the gene called Dicer, which is the catalytic engine of small RNA production in cells. We are using this mouse to explore the role of small RNAs in developmental and immune biology settings. The roles of small RNAs may be much broader than anticipated, thus Dicer may be a 'master regulator' in a number of different contexts. Genetic data in C. elegans indicates that Dicer depletion results in loss of the ability to do RNA interference and developmental defects. In S. pombe, knockout of Dicer results in loss of heterochromatic silencing, suggesting a potential role for small RNAs in transcriptional gene silencing. In fact, evidence is accumulating that small RNAs may be key mediators in DNA methylation. We believe that the small regulatory RNAs that have discovered are just the 'tip of the iceberg' in a set of important biologies that we are far from understanding.
Current projects include the use of RNA expression arrays (both mRNA and microRNA), mouse transgenics (both knock-outs and knock-ins), and biochemical approaches in cell culture aimed at dissecting mechanisms of small RNA biology.
Other Research in Dr. McManus's Lab
Tumor Immunology
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Jennifer Puck
Jennifer Puck, MD, came to UCSF in 2006 as Professor of Pediatrics in the Division of Immunology and Rheumatology and Associate Program Director for Pediatrics in the CTSI Clinical Research Center. Dr. Puck¹s research is in human primary immunodeficiencies. Her scientific contributions include mapping and identification of the genes for X-linked severe combined immunodeficiency (XSCID) and autoimmune lymphoproliferative syndrome (ALPS); a clinical trial of retroviral gene therapy for patients with XSCID who failed bone marrow transplantation; and definition of the disease and gene defects in STAT3 in hyper-IgE syndrome, or Job's syndrome, a multisystem disorder. On the translational side, she has developed a test to screen all newborns for severe lymphocyte disorders and is planning a large pilot trial. Dr. Puck also uses mouse models to probe lymphocyte development and is investigating a new gene identified by her lab that when knocked out results in arrest of T cell development from common lymphoid presursors.
Other Research in Dr. Puck's Lab
Diabetes and Autoimmunity • Immune Receptors and Signaling
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Jeroen Roose
Our lab studies how lymphocytes make "yes versus no" decisions (immune responses) and how the controlled nature of this process can be lost (autoimmune disease or leukemia/lymphoma). We study these processes at the level of Ras activation, which is a sensitive signaling switch that is strongly triggered after antigen receptor stimulation. In addition, we investigate how Ras activation in the basal state regulates gene expression programs.
We strive to unravel the details of regulated and deregulated Ras activation using cell lines, mathematical models, mouse models, and patient samples.
Other Research in Dr. Roose's Lab
Immune Receptors and Signaling
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Steve Rosen
Dr. Rosen’s lab is studying two extracellular sulfatases (Sulf1 and Sulf2) which act on heparan sulfate proteoglycans. These enzymes appear to be involved in regulating the Wnt signaling pathway. Dr. Rosen’s lab is studying the role of these enzymes in multiple myeloma and other cancers where the Wnt signaling pathway is dysregulated.
Other Research in Dr. Rosen's lab:
Immune Receptors and Signaling • Inflammation • Tumor Immunology
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Matthias Wabl
Gene-targeted mice with a simplified immune system
Clonal selection demands that individual B cells be monospecific. Allelic and isotypic exclusion ensure that there is but one functional heavy (H) chain and one functional light (L) chain gene. While there is general agreement that allelic and isotypic exclusion of L chain is accomplished by turning off the enzymes that assemble the genes from gene segments, various competing theories have been proposed to explain allelic exclusion at the H-chain locus. The goal of our experiments is to assess the contributions of the stochastic, genetic regulation, and cellular regulation models to the understanding of allelic exclusion at the immunoglobulin H-chain locus.
We test the various hypotheses in the monoclonal B-cell mouse generated by nuclear transfer from a B lymphocyte. In these experiments, the H and L alleles from the original B lymphocyte is shuffled and combined with germ line or nonfunctional alleles. The aim is to create mice that represent various pre-B- and B-cell genotypes, and to investigate the effect of the various preformed alleles on the germ line or rearranged allele(s) and on B-cell development as it relates to allelic exclusion.
Other Research in Dr. Wabl's lab:
Immune Receptors and Signaling • Inflammation
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Arthur Weiss
Null mutants in Src and Syk tyrosine kinases as well a transmembrane tyrosine phosphatases have taught us that these molecules play key roles in developmental checkpoints and in regulating immune responses. However, we don’t really understand how they are controlled during development and during an evolving immune response. Projects are aimed at understanding the specific and redundant roles of molecules of these families.
Other Research in Dr. Weiss's Lab
Diabetes and Autoimmunity • Immune Receptors and Signaling
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Zena Werb
The Werb lab is interested in the role of the innate immune suystem (macrophages, mast cells) in mammary gland development and involution.
Other Research in Dr. Werb's lab
Immune Response to Microbial Pathogens • Inflammation • Tumor Immunology
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