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Living organisms are consisted of cells containing a number of proteins expressed from a series of genes. Signal transduction is required for cells to maintain their communication among cells. This signal transduction regulates the network of proteins and the aberration of signaling may lead to a number of diseases such as cancer, diabetes, Alzheimer’s disease, and infertility.
1. Cancer and Stem Cell Biology : Ubiquitin-Proteasome System (Deubiquitinating Enzymes)
Cell growth and differentiation for human stem cells are regulated by growth factors and cytokines that induce the expression of specific target genes. Some genes directly control mitogenesis. Others regulate intracellular proteolysis, allowing a cell to rapidly switch from one physiologic state to another. Ubiquitin mediated proteolysis is an important mechanism for regulating cellular progresses in all eukaryotic cells. Polyubiquitinated proteins are recognized and degraded by the 26S proteasome, a multi-subunit protein degradation complex. They are regulated by a reverse mechanism, deubiquitination. Recently, these mechanisms have been implicated in a diverse assortment of processes, including cell cycle regulation, transcriptional activation, DNA repair, antigen presentation and so on.
People in the laboratory of Molecular Signal Transduction Laboratory are investigating the molecular mechanisms of DUB enzymes (deubiquitinating enzymes) that may regulate the protein degradation in signaling pathways and cell proliferation and differentiation for embryonic and adult stem cells of human and mouse. Recently, we isolated and characterized novel DUB genes including mHAUSP, HeLaDUB-1, USP36, USP22, USP17, and USP42, and are now investigating their functional roles. The goals of our projects are to develop ways of cell proliferation and differentiation for embryonic and adult stem cells and lymphocytes.
2. Cancer Biology: Recessive Oncogene Lethal Giant Larvae (Lgl) Family Members
In order to understand the mechanisms of cancer development and metastasis, researchers have been trying to identify and study tumor suppressor genes and proto-oncogenes in various living organisms. The lethal (2) giant larvae (l(2)gl), the first recessive oncogene found in Drosophila, has been known that homozygous mutations at this locus lead to the development of transplantable neoplasms. The l(2)gl homologues in other organisms have been identified including Saccharomyces cerevisiae, Caenorhabditis elegans, mouse mgl-l, and human hugl. Since there are conserved structure of genes, the similarity of cellular processes, and functional conservation of proto-oncogenes and tumor suppressor genes among different species, it is possible that delineating the mechanisms of cancer development and metastasis in lower animals such as mice and rats can directly contribute to the understanding of them in human.
3. Reproductive Biology: Recurrent Pregnancy Loss (RPL), Premature Ovarian Failure, and Polycystic Ovary Syndrome (PCOS)
Recurrent pregnancy loss (RPL) is defined as the occurrence of a clinically detectable pregnancy loss within 20th weeks' gestation on 3 or more occasions. However, in as many as 40-60% of these cases, the cause remains unknown. This research project will be involved in identifying and cloning the factor(s) that are less expressed or more expressed in RPL patients. The scientific and clinical benefits of this effort will ultimately enable the physician to more effectively address the uncertainty that confronts patients experiencing habitual abortion.
Premature ovarian failure (POF) is defined when a female achieves menopause before the age of 40, ultimately resulting in infertility. Since no biomarkers for POF have been identified to date, this research project is developed to investigate the biological functions of proteins differentially expressed in POF patients.
Polycystic ovary syndrome (PCOS) affects 5% of reproductive aged women and is the leading cause of anovulatory infertility. Recently, it has become clear that this syndrome is also associated with obesity, hirsutism, and insulin resistance as well as menstrual disturbance. The clinical and biochemical features of this syndrome are heterogeneous, which lead to much debate as to whether it represents a single disorder or several. This research project will be involved in identifying and cloning the factor(s) that are less expressed or more expressed in PCOS patients.
To achieve these goals for our projects, basically molecular, biochemical and immunological techniques including gene cloning, sequencing, PCR (polymerase chain reaction), RT-PCR, Southern blotting, Northern blotting, Western blotting, 2-DE, mass spectrometry, and cell culture are applied.