Rotation Programs
Sue Ackerman's laboratory studies the molecular mechanisms underlying CNS development and neurodegeneration utilizing both forward and genetic approaches. Graduate student projects include the examination of the molecular and biological mechanisms underlying the CNS dysfunction in various mouse mutant strains.
Yaki Barak’s lab studies the molecular mechanisms of action of the nuclear hormone receptors PPARgamnma and PPARdelta in placental development and fat cell differentiation. By integrating different gene knockout methodologies, stem cell cultures and differential gene expression screening paradigms, his lab has identified multiple target genes of both PPARs in the placenta and fat cell progenitors. His lab currently focuses on: (i) the in vivo functions of these genes through generation and analysis of knockout mice; (ii) the mechanisms that underlie the transcriptional regulation of target genes by PPARs. Diverse rotation and graduate projects can be chosen within these focus areas.
Joerg Bewersdorf's lab is developing and applying novel biological light microscopes with unprecedented three dimensional or temporal resolution. In particular, the lab houses the only Leica 4Pi microscope in the United States featuring 100 nm axial resolution, a factor of 6 better than conventional microscopy. Student projects available in the lab include the application of these novel techniques to a variety of biological collaborative projects, feasibility studies for new applications, and the development and test of additional optical or software-based features of the new instruments.
Judy Blake welcomes rotation students to work on questions in knowledge representation such as 'how do we represent the similarities and differences in branching morphogenesis in development of different organ systems. Students will work as part of an international collaboration that is implementing controlled vocabularies to support comparative genomic studies by analysis of shared functional annotations. Projects include both development of classifications, and analysis of integrated datasets for processes such as embryogenesis.
Carol Bult’s research group focuses on two major areas: bioinformatics and developmental genomics. In the area of bioinformatics the focus is on building information systems that can facilitate the use of the laboratory mouse as a model system for understanding normative biology and disease processes in humans. Student projects in this area will involve implementing new or improved methods for data analysis and visualization. In the area of developmental genomics, the lab focus is on using molecular genetics of normal lung development in mouse as a framework for identifying key genes and pathways in lung diseases such as cancer and pulmonary fibrosis. Student projects in this area will center on identifying patterns in genome scale data that are relevant to pulmonary disease.
Rob Burgess focuses on a fundamental question of neurobiology: what are the molecular mechanisms underlying the formation and maintenance of synaptic connections? He addresses this question in vivo using the retina and peripheral nervous system of mice as an experimental model, and in vitro using a variety of quantitative cellular assays. Students in the lab have the opportunity to learn genetics, microscopy, cell biology or molecular biology, depending on their interests. Training opportunities in the lab in addition to hands-on research include interaction with research scientists, postdoctoral fellow, and research assistants, as well as a group meeting and seminars conducted jointly with other neurobiology researchers at The Jackson Laboratory.
Bob Braun focuses on germ cells, highly differentiated cells that have the unique ability to create a new organism. This totipotent potential is acquired and maintained by several mechanisms during embryogenesis and in the postnatal gonad. Dr. Braun’s lab is interested in (1) the genetic and epigenetic mechanisms that maintain the balance between germline stem cell self-renewal and differentiation, (2) hormonal signaling between the soma and the germline, especially in regards to creating specialized niches, or compartments, that are both permissive and instructive for germ cell differentiation, and (3) molecular mechanisms of posttranscriptional regulation, especially those that involve temporal protein synthesis. We use both genetics and biochemistry to investigate biological mechanisms. Rotation projects involve working with a pre-doctoral student or post-doctoral investigator in one of these research areas. Projects are designed to introduce the rotation student to the broad biological question and to train students in experimental design, specific scientific methods, data collection and data interpretation.
Casey Fox’s lab is investigating new ways to control the growth of blood cell cancers. The focus is on understanding how mature lymphocytes are able to reversibly transit between highly proliferative and quiescent states. The ultimate goal of this research is to discover a way to reprogram transformed cells to enter and remain in a dormant state. His laboratory studies two signaling pathways that appear to be universal regulators of growth and division in most cell types. Projects available for study include investigating (from a biochemical perspective) how these two pathways cooperate to promote the growth of normal and transformed mature B and T cells and their precursors.
The long term goals of Greg Cox’ research program are to identify molecular pathways necessary for the normal function and survival of motor neurons and their skeletal muscle targets. Muscular dystrophies and motor neuron diseases collectively have a high impact on health, affecting tens of thousands of people in the United States alone. The diseases are characterized by weakness and progressive wasting of muscles eventually leading to paralysis and death. We have chosen to focus on the resources available at The Jackson Laboratory in the form of spontaneous and induced models of neuromuscular disease as our starting point for gene discovery and functional analysis. This phenotype-driven approach ensures that the mutant genes we identify are critical for the normal development and/or maintenance of motor neurons and skeletal muscles.
Wayne Frankel's lab is focused on the molecular basis of epilepsy, by studying mouse strains and mutants that have different forms of this disease. One current interest is in genetic variants that cause and modify the function of the corticothalamic network, leading to absence (a.k.a. petit-mal) epilepsy, including mutants such as stargazer, tottering and absence-prone mouse strains such as C3H/HeJ. The laboratory is also interested in molecules that regulate gene expression in the brain, whose disruption consequently leads to seizure disorders, and in understanding the role of brain development in seizures that occur in adults.
Joel Graber's lab uses a variety of computational approaches to investigate gene regulation and gene interaction networks. Working in the context of the Center for Genome Dynamics, his group is integrating large-scale datasets regarding the interactions between different regions of the mouse genome, and trying to understand the role that optimization of the interaction network has played in organization of the genome. In addition, his group has several efforts to characterize and model post-transcriptional regulatory signals and interactions. These studies span multiple model organisms, with current efforts focused on mouse, zebrafish, fission yeast, and nematode. Rotation projects are available in any of these areas, and can be tailored to expose the students to a variety of computational approaches and tools.
Tom Gridley’s laboratory studies evolutionarily-conserved signaling mechanisms, and their roles in embryonic development, disease and cancer. His laboratory creates and analyzes genetically engineered mouse models to understand the essential functions of individual components of these signaling pathways. Rotation projects include analyses of these models using techniques such as histopathology, in situ hybridization and immunohistochemistry.
David Harrison’s research in gerontology tests hypotheses about the causes of aging in mice. The hypothesis that Insulin and IGF-1 each have specific contributions to aging is tested by combining mutations that reduce function of both pathways in specific tissues. His group determines the genes and mechanisms responsible for greatly increased female reproductive life spans in Pohn x B6 F2 populations, and the genes and mechanisms responsible for greatly increased total life spans in WSB x SKIEVE F2 mice. His group is also part of a consortium testing interventions that may retard aging. His research in hematology focuses on cellular and molecular mechanisms that regulate differentiation, self-renewal, and aging in stem cells. His group tests whether defects with age in BALB but not B6 marrow hematopoietic stem cell (HSC) functions are intrinsic within the stem cells, and whether they occur due to genomic instability, proliferative exhaustion or retarded apoptosis. Similar experiments test how diet restriction greatly improves hematopoietic stem cell functions in old BALB mice, while also reducing cancer. Students on rotation projects will learn to do and interpret original experiments in these areas.
Simon John's group determines mechanisms that induce neurodegeneration. The major focus is on glaucoma, a common blinding disease that kills retinal ganglion cells and affects 70 million people. Glaucoma is often associated with a harmfully elevated pressure in the eye (intraocular pressure, IOP). Both the mechanisms of IOP elevation and retinal ganglion cell death are poorly understood. Different projects are available that include the characterization of new mutants with high IOP and the study of neurodegenerative mechanisms. Projects are also available to understand a potent neuroprotection induced by a radiation treatment and to assess various drug therapies.
Shaoguang Li's lab is focused on understanding molecular basis of leukemia induced by the BCR-ABL oncogene that is responsible for induction of human PH+ leukemia. His lab has identified some key signaling molecules involved in leukemogenesis, some of which are potential targets for leukemia therapy. Dr. Li's lab has taken new approaches to study the biology of leukemic stem cells, aiming to develop novel therapy by targeting these stem cells.
Kevin Mills’ lab is studying mechanisms and control of genome stability as they pertain to tumor suppression or tumor development. His work focuses primarily on genome stability defects in lymphoid cells, using two major genome instability models: mice that lack factors involved in the nonhomologous end joining pathway of DNA repair; and mice that contain mutations in the homologous recombination gene Xrcc2. Currently there are a number of projects in the lab organized around these themes. Possible rotation projects include:
1. Measuring hematopoietic stem cell or mesenchymal stem cell populations in mice with engineered defiencies in DNA double strand break repair.
2. Generating and testing constructs for genetically tagging chromatin proteins with photoactivatable fluorescent tags, to be used for in vivo studies of DNA damage response and genome instability
3. Conducting molecular and cytogenetic characterization of cancer-derived cell lines to evaluate the possible role of the homologoux recombination factor Xrcc2 in oncogenic genome instability.
Patsy Nishina's lab is focused on identifying molecules important in the development, function and maintenance of the neuroretina. Currently, her laboratory has assembled a group of mutants with eye phenotypes similar to that observed in humans in a chemical mutagenesis screening program. The identification of the underlying mutations in these models as well as the discovery of the function of the mutant proteins and the mechanisms leading to the pathological changes observed are projects available for study in her laboratory.
Luanne Peter's lab is focused on identifying genes critical in hematopoiesis, the process of blood formation. Specifically, Dr. Peters' group focuses on inherited red cell defects causing hemolytic anemia (e.g., hereditary spherocytosis, sickle cell disease, iron deficiency) and on inherited platelet function deficits that cause abnormal bleeding syndromes such as Hermansky-Pudlak syndrome. The group identifies single gene defects that adversely impact red cell and platelet formation. In addition, Dr Peters studies hematopoiesis as a complex trait in order to identify genetic modifiers of baseline blood counts, which are significant risk factors for cardiovascular disease and stroke.
Derry Roopenian’s lab is interested in understanding the genetic and cellular basis of autoimmune diseases, including lupus, arthritis, and transplant rejection. We use a combination of forward and reverse genetic approaches to identify and characterize the key genes that contribute to these diseases. We then use genetically engineered mice to help us to develop therapies to treat the diseased mice. Project opportunities include: (1) the role of the mutation, Yaa, in lupus; (2) the role of the novel cytokine, Interleukin 21, in lupus and other autoimmune diseases; (3) the mechanism by which the Fc receptor, FcRn, controls antibodies.
The focus of Dave Serreze’s laboratory is to dissect the genetic basis for aberrations in immunological tolerance that underlie the development of autoreactive T cell responses causing type 1 diabetes (T1D) in the NOD mouse model. One of our investigations is to determine why some common major histocompatibility complex class I molecules, also present in many strains lacking autoimmune proclivity, when expressed in NOD mice aberrantly lose the ability to mediate processes that would normally eliminate T1D inducing T cells. We are also studying the basis for defects in various classes of antigen presenting cells in NOD mice that impairs their ability to normally induce immunological tolerance. Graduate student rotation projects are available in either of these areas.
Lindsay Shopland’s lab has several projects available for prospective students. We study chromosome 3D structure and nuclear organization. Students can test the roles of gene activity and epigenetic state on chromosome structure. In addition, the contributions of nuclear filament proteins on chromosome structure can be examined using cells from mice carrying mutations in these genes. Finally, students can choose to work on high resolution imaging of the nucleus using the new 4Pi microscope.
Len Shultz. Advances in our understanding of the development and regulation of the immune system in normal and pathologic states rely heavily on studies of mice with genetically determined immunodeficiency and autoimmunity. Research in our laboratory encompasses (1) basic studies focused on elucidating the mechanisms underlying immunodeficiency, autoimmunity, and hematological diseases; and (2) applied studies focused on the development of effective immunodeficient mouse models that support heightened engraftment with human hematopoietic stem cells. These "humanized SCID mice" will facilitate studies of human immunity, regenerative medicine, and neoplasia.
John Sundberg’s lab group focuses on genetically based skin diseases including autoimmune diseases (alopecia areata), psoriasis-like diseases, and blistering diseases (epidermolysis bullosa) and on the genetics of diseases of aging. We carefully define spontaneous and genetically engineered mouse models with specific human diseases, identify the genes involved, define the pathogenesis, then develop these models as preclinical tools for screening existing drugs predicted to work based on our molecular studies.
Kyuson Yun’s laboratory is interested in identifying molecules and mechanisms that regulate normal neural stem cells and cancer stem cells. There are several rotation projects in the lab including: 1) characterization of mouse mutants that have a defective neural stem cell compartment; 2) validation of putative novel biomarkers for cancer stem cells; 3) generation/characterization of novel antibodies against cancer stem cells; 4) defining cellular and molecular characteristics of cancer stem cells during tumor progression; 5) determining the role of Notch signaling in maintenance of neural stem cells.
Zhong-wei Zhang's lab interested in the maturation and plasticity of neuronal connections during development. The two major areas of research are: 1) molecular mechanisms underlying the elimination and consolidation of synapses in the brain, and 2) synaptic mechanisms underlying developmental brain disorders. We use a combination of electrophysiology, anatomy, molecular biology, and mouse genetics.
