Development & Differentiation

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 AsthmaImmune Regulation

 

Jason Cyster 

Our group studies the role of chemokines and lipids guidance cues (lysophospholipids and oxysterols) 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 and function.

Other Research in Dr. Cyster's Lab:

Diabetes and AutoimmunityImmune RegulationImmune Receptors and SignalingImmune Response to Microbial Pathogenesis 

  

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 RegulationImmune Response to Microbial PathogensInflammation 

 

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 

 

Emmanuelle Passegué

During steady-state hematopoiesis, the self-renewing blood-forming hematopoietic stem cells (HSCs) give rise to non self-renewing multipotent progenitors (MPPs), which produce balanced levels of lineage-committed lymphoid and myeloid progenitors and homeostatic levels of all mature blood cells. However, this “classical” pathway of HSC differentiation fails to fully explain the massive myeloid expansion observed in a broad range of myeloid disorders, which usually occurs without an accompanying increase in lymphopoiesis. We are interested in investigating alternative pathways of myeloid differentiation to understand how changes in early lineage specification from HSCs contribute to the development of myeloid disorders. 

Other Research in Dr. Passegué's Lab:

Immune RegulationInfammation 

 

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 AutoimmunityImmune Receptors and Signaling  

 

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 

 

Jeoung-Sook Shin 

Regulatory T cells play important role in immune homeostasis and tolerance. The Shin lab studies how dendritic cells contribute to regulatory T cell development and function.

Other Research in Dr. Shin's Lab:

Allergy and Asthma • Immune Receptors and Signaling 

 

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 SignalingInflammation  

 

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 AutoimmunityImmune Receptors and Signaling  

 

Zena Werb 

The Werb lab is interested in the role of the innate  and adaptive immune systems (macrophages, mast cells, T-cells, dendritic cells) in mammary gland development and in lung repair of injury. The discovery of a normal developmental role for the adaptive immune response during tissue development opens a new research area that has implications for autoimmunity.

Other Research in Dr. Werb's Lab:

InflammationTumor Immunology 

 

Julie Zikherman

 

Our laboratory is interested in understanding how the normal repertoire of B cell antigen receptors is established during B cell development and how this process is disrupted in autoimmune disease. To do so, we are taking advantage of novel reporter mice in which autoreactive B cells are fluorescently marked. We are combining these reporters with receptor cloning, transcriptome profiling, biochemical analysis of signal transduction, and genetic mouse models in order to dissect how autoreactivity is selected and counterselected in the mature B cell repertoire.

 

Other Research in Dr. Zikherman's Lab:

Diabetes and AutoimmunityImmune Receptors and Signaling