Main Menu

Leucine rich repeats and calponin homology containing protein 4 (Lrch4) is a gene that encodes a protein predicted to have a C-terminal transmembrane domain, a calponin homology domain, and 5-8 leucine rich repeats (LRRs). We silenced Lrch4 in RAW 264.7 macrophages as well as CD14-MD2-TLR4-HEK293 cells and found that Lrch4 knockdown attenuates responsiveness of cells to LPS and other pathogen-associated molecules. These findings suggest that Lrch4 is a regulator of the innate immune response.

CAR (nuclear constitutive active receptor) is a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. It is primarily responsible for sensing foreign toxic substances and in response up regulating the expression of proteins involved in the detoxification and clearance of these substances from the body. CAR is constitutively active in the absence of a ligand but is regulated by both agonists and inverse agonists.

Tristetraprolin (TTP) is the prototype member of a small family of RNA binding proteins that bind to specific types of AU-rich elements in the 3'UTRs of target mRNAs and promote their rapid turnover. One of the targets destabilized by TTP is Tumor necrosis factor alpha (TNF). TNF has long been a target of anti-inflammatory drug development, in which recombinant protein molecules based on TNF antibodies or TNF receptors have been used to bind directly to TNF and inactivate it.

Electron Spin Resonance (ESR) is an universal, specific tool for the detection of free radicals in biological systems. Its application to the investigation of free radicals from whole animals, organs, and cells has been made possible by the spin-trapping technique. In a Spin-trapping experiment, a spin trap such as DMPO (5,5-dimetryl-1-pyrroline N-oxide) reacts specifically with one or more types of free radical to form radical-derived nitrone adducts that are much more stable than the original free radicals.

Mutations in the p53 gene are associated with 50% of all cancers and nearly 80% of the p53 mutations are missense changes. We have developed genetic assays based in yeast that can functionally categorize expressed p53 mutant proteins. The combined assays are referred to as the FIP53 system. Because human p53 cDNA can be conveniently cloned in yeast, the FIP53 system provides a rapid and sophisticated system for the functional analysis of p53 mutants. Four categories of mutations have already been identified.

Tristetraprolin (TTP) is involved in the physiological regulation of the secretion of at least two important cytokines, tumor necrosis factor alpha (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). TTP exerts its effects by directly binding to the mRNAs encoding these proteins and destabilizing them, resulting in less secretion. Conversely, TTP deficiency results in an excess of both cytokines, leading to a systemic inflammatory syndrome.

SIRT1, a NAD+-dependent protein deacetylase, is the most conserved member of the sirtuins family. Through deacetylation of a number of protein substrates that are important transcription factors or co-factors, SIRT1 regulates many vital biological processes such as metabolism, cellular stress response, stem cell pluripotency, and development.

Diabetic nephropathy (DN) is the leading cause of renal failure and is characterized by proteinuria that progresses to renal inflammation and decline in the glornerular filtration barrier (GFB). Podocytes are specialized epithelia cells in the glomerular capsule that have a role in filtration of blood and maintaining the integrity of the GFB; dysfunction of these cells plays a significant role in the pathogenesis of DN. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition has beneficial effects in inflammatory diseases.

Heterotrimeric G proteins couple signals between GPCRs (G protein coupled receptors) and effectors such as adenylyl cyclase, phospholipase C and ion channels. Among the G proteins are Go and Gi2. Go is highly expressed in the brain and some endocrine tissues while Gi2 is widely expressed throughout the body. The ß?-subunits of Go interact with ion channels, and the a subunit has been shown to inhibit adenylyl cyclase. However a physiological role of the Gi2a has not been determined in a tissue specific manner.

TRPCs (Canonical Transient Receptor Potential Channels) are a group of non-selective cation channels that allow sodium and calcium into cells. There are seven different genes in mice that code TRPCs. The in vivo roles played by TRPCs as a whole are poorly understood and very little is known about the in vivo roles played by individual TRPCs nor the role of these channels in specific tissues or cells.