Our research focuses on delineating the role of the MAP kinase pathways in controlling microglial cell production of inflammatory mediators, and how hypoxia and hypoxia and reperfusion injury modulate the activity of purinergic P2 receptors for extracellular ATP and their signaling pathways. Selective alterations in the activity of purinergic receptors may provide a novel therapeutic target that can be exploited to minimize damage to the brain following ischemic injury.

Other goals of our research center on delineating the anti-inflammatory effects of estrogen on microglial cell activation at the molecular level, by dissecting the signal transduction pathways and receptors that are modulated by estrogen in activated microglial cells. Defining the molecular mechanisms involved in the estrogen modulation of microglial cell activation and their production of inflammatory mediators, may lVisad to the identification of novel therapeutic targets that can be exploited to minimize the brain damage ensuing from neurodegenerative diseases and other brain disorders, to which women are predisposed.
Visit the Watters Lab website: http://www.vetmed.wisc.edu/cbs/watters2/index.htm

Dr. Judd Aiken is a faculty trainer in the CMB Program. Read the full news article at http://www.news.wisc.edu/1391

Aiken Lab Research Description

We have two major projects in my laboratory: i) the involvement of mitochondria in the aging process and ii) the molecular characterization of the scrapie agent. We are testing the hypothesis that mitochondrial DNA is a "weak link" in the aging process. We are examining two animal species, the mouse and the rhesus monkey for the presence of age-associated mtDNA abnormalities. We have identified age-associated mtDNA deletions in both species. These age-associated deletions appear to be most pronounced in nerve and muscle and hold great promise for explaining the major diseases and disorders old age brings to these tissues. Our current efforts involve quantification of deletion abundance and correlation of deletions with changes in cellular morphology. Transmissible spongiform encephalopathies (TSEs) are fatal neurologic disorders that are characterized by extended incubation periods, of months to years, followed by rapid progression of clinical symptoms. TSEs affect a wide range of animal hosts with scrapie, in sheep and goats, being the most common natural TSE.

Read the full research arcticle at http://www.news.wisc.edu/13995

Dr. Paul Ahlquist is a faculty trainer in the CMB Program.

Ahlquist Lab Research Description: We are studying the novel, RNA-based pathways and virus-host interactions underlying replication, gene expression and evolution by positive-strand RNA viruses, the largest class of viruses. Positive strand RNA viruses include many important human pathogens such as hepatitis C virus, which chronically infects nearly 3% of the world population, causing progressive liver damage and liver cancer, and the new SARS coronavirus. We are also studying selected replication processes of a reverse-transcribing virus, hepatitis B virus, which is also a major human tumor virus. Our studies integrate molecular genetics, genomics, biochemistry and cell biology to address fundamental questions in virus replication and virus-cell interactions. See more at the Ahlquist Lab website

Dr. Robert Striker is a faculty trainer in the CMB Program. Read the full research article at http://www.news.wisc.edu/13928

Striker Lab Research Interests

RNA viruses have high mutation rates and robust replication so they evolve rapidly to adapt to the exact cellular conditions of the host. Therefore RNA viruses are a challenge to the human immune system, as well as drug and vaccine development. We study the molecular details of what portions of the viruses are susceptible to evolutionary pressure.

When Hepatitis C Virus (HCV) infected patients require a liver transplant, the new liver also becomes infected and represents a unique “fast-action, real world camera” on evolutionary change in viruses. The input virus can be characterized, and monitored as it adapts to an immune system blocked by immunosuppressants, and a new liver. We have identified some of the genetic barriers the virus must overcome and how they are overcome in the lab.

The central question our lab intends to answer is how functionally diversified neuronal and glial subtypes are born in the human nervous system. We approach this question by the use of (primate and rodent) embryonic stem (ES) cells that are derived from the inner cell mass of a pre-implantation embryo. We have developed model systems in which ES cells differentiate to multipotential early neuroectodermal cells and then region-specific and subtype-specific neural progenitors in a chemically defined environment, which recapitulates the early phase of neural development in temporal course, morphological transformation, and gene expression patterns. This suggests that some of the intrinsic program of neural differentiation is preserved in our culture model system. Using these model systems, we are dissecting molecular mechanisms underlying the process of neuroectoderm induction and neuronal subtype specification.
Zhang Lab website http://www.waisman.wisc.edu/scrp/zhang.html

Our laboratory studies microbial biochemistry with an emphasis on understanding the molecular mechanisms that give rise to phenotypes in bacteria. Although our current understanding of the complexity of a bacterium is still emerging, it is becoming clear that the genetic and biochemical mechanisms that govern cellular homeostasis are far more sophisticated than we had imagined. Our approach to the study of bacteria is driven by the development of new capabilities for studying single cells or small groups of cells and the application of these techniques to dissect the molecular choreography within the cell. This research is interdisciplinary and is based on a fusion of techniques from biology, physics, engineering, and chemistry.

The top-level goal of our research is to understand how the behavior and physiology of bacteria is encoded at the molecular level. The results of these projects drive the application phase of our research, which is aimed at using bacterial cells to produce new materials. We summarize several areas we are working on below.

Weibel Lab website: http://www.biochem.wisc.edu/faculty/weibel/

 

 

My lab studies regulation of gene expression by the EGR (early growth response) transcriptional activators. Several groups have identified human EGR2 mutations that cause myelination disorders of the peripheral nervous system such as Congenital Hypomyelinating Neuropathy (CHN), Charcot-Marie-Tooth Disease (CMT), and Dejerine-Sottas Syndrome (DSS). Association of EGR2 mutations with such myelination disorders is consistent with the phenotype of EGR2/Krox20 knockout mice which also exhibit a profound myelination defect. However, an unexpected result was that most of the EGR2 mutants in the human diseases appear to exert a dominant negative effect, and we are currently characterizing the molecular interactions that are responsible for this phenomenon. EGR2 has been identified as a master regulator of a diverse array of myelin-associated genes, and we have recently been able to use chromatin immunoprecipitation (ChIP) to localize EGR2 binding sites in myelinating peripheral nerve in vivo, and we are using this technique to explore interactions with other transcription factors and histone modifications in myelin genes.

 

Cell division is required for the propagation of all living things. A critical phase of cell division occurs just after segregation of the duplicated genome, when the chromosomes, cytoplasm and organelles are partitioned to two daughter cells in a process termed cytokinesis. In animal cells, cytokinesis is driven by a cortical contraction that hysically pinches the cell in two, and requires coordination of the mitotic spindle, actin cytoskeleton and plasma membrane. Failures in cytokinesis can cause cell death and age-related disorders, or lead to genome amplification characteristic of many cancers. Although cytokinesis has been studied for over 125 years, little is known about the molecular factors and mechanisms involved.

My laboratory integrated multiple approaches in both mammalian tissue culture cells and C. elegans systems to identify and characterize conserved factors, taking advantage of proteomics, functional genomics, genetics, cell biology and video-microscopy techniques.

Skop Lab Website: http://skop.genetics.wisc.edu/