Dr. Filtz’s general research interest is in how a cell receives a signal and then transmits that signal to alter its function in response. She is more particularly interested in how signaling molecules/proteins are altered to change their activity. In collaboration with the lab of Dr. E. Woodcock in Melbourne, Australia, Dr. Filtz has explored the role of increased levels of phospholipase C-beta, a ubiquitous signaling enzyme, in the development of atrial fibrillation as a potential drug target. In collaboration with Dr. Mark Leid in the College of Pharmacy at OSU, Dr. Filtz is studying the regulation of a tumor suppressor protein, Bcl11b. Bcl11b is critical for the proper development of T cells in the immune system; loss of Bcl11b is associated with a childhood cancer, T-cell acute lymphoblastic leukemia (T-ALL). Additionally, Dr. Filtz has been involved in screening natural product compounds for direct action on heart cells. She has shown that two different plant products, an herbal extract of hawthorn tree, and the chemical berberine from various plant sources including Oregon grapes, both have a direct action on cardiomyocytes through classic receptor subtypes.
Research Interest: Cutaneous injury, repair, and regeneration, cross-talk between epidermal and mesenchymal cell, cell proliferation, migration, stem cell mobilization and cancer. The long-term goal of this lab is to elucidate the cellular and molecular mechanisms that underlie chronic wounds, inflammation, and cancer for developing novel therapeutic targets for diseases and cancer and to improve human health. Transcription factor CTIP2 plays essential roles in epidermal homeostasis, barrier formation, and cutaneous wound healing. In collaboration with Drs. Leid and Arup Indra in OSU, we are identifying Ctip2-regulated novel genes and signaling pathways in epidermis and hair follicle niches that can promote effective scar-free wound healing. Those identified factors will serve as potential therapeutic targets for pharmacological manipulation to accelerate the wound-healing process in human patients and promote efficient wound repair and tissue remodeling. We have also set up various in vitro assays using a spectrum of early-stage and metastatic cancer cell lines to screen natural compound libraries that are obtained from our OSU Colleagues Dr. Mahmud and Dr. Stevens for potential discovery of novel anti-cancer drug leads. More specifically, we will study if the identified natural compound(s) compounds are able to target the cancer stem cells. We are also studying their effects on cell proliferation, cell cycle distribution, senescence, apoptosis, angiogenesis, and inflammation and expression levels of several biomarkers by RT-qPCR western blot and ELISA assay.
The Kioussi laboratory is interested in defining the gene regulatory networks involved in muscle development and energy balance systems towards the goal of developing new strategies to treat dystrophies and metabolic syndromes. A complex transcriptional network transforms stem cells, through an organized series of embryonic cell types, into adult cell types. Genetic variation is a major cause of development, diversity and disease susceptibility. Epigenome determines the pattern of gene expression and gives the cell its distinct characteristics, function, and behavior. We use a combination of biochemical, genetic, genomic and computational approaches to dissect the roles of transcription factors involved in organ development and tissue regeneration. Our studies will serve as the foundation for the development of future strategies and pharmacological interventions that influence the maintenance and differentiation potential of cell populations in patients with disrupted metabolic fuel homeostasis and muscle atrophy.
Our laboratory is investigating the mechanisms of skin development in space and time from stem cells using genetics, biochemical, cellular and molecular approaches. In collaboration with Mark Leid, we have discovered that transcriptional regulatory proteins CTP2 and CTIP1 regulate key processes during skin formation. Their mechanisms of activation in response to external cues and roles in integrating with multiple signaling cascades are areas of active research. We have identified key factors that are essential to maintaining a balance in the skin, lack of which can lead to childhood mortality or can trigger the onset of inflammatory skin diseases such as Atopic dermatitis (AD). The mechanisms of protective skin barrier formation and contribution of skin cells in triggering immune responses are being investigated. A lipidomics approach for profiling skin lipids and predicting ADprogression is underway in collaboration with faculties at OHSU and OSU. We are studying the (a) mechanisms by which these developmental processes are deregulated in cancer, and (b) cell-cell signaling functional within a tumor nanoenvironment that contribute to cancer metastasis. We discovered that nuclear receptor (NR) signaling between skin cells contribute to the formation of malignant melanomas. The crosstalk between NR signaling and other signaling pathways to mediate metastasis and de-differentiation are being investigated. We developed multiple pre-clinical models of human diseases exhibiting skin barrier defects, atopic dermatitis, skin pigmentation disorder, and for invasive melanomas. In collaboration with faculties in medicinal chemistry (Taifo Mahmud, Fred Stevens) and Pharmaceutics, we are utilizing these models to screen for natural compounds as new drug leads and develop nano-carriers for effective therapeutic intervention.
meaningful question by applying large-scale tools to measure as many characteristics as possible without preexisting biases; then to analyze the data by a variety of methods, and to follow up with further study. In these studies, we use a top-down approach, spanning a multitude of different scales and techniques, varying from molecular/genetic analysis of human diseases to in vivo and in vitro analysis of mouse models. The laboratory uses both established and novel algorithms for analysis of large-scale biological data. Most recently we have used the concept and tools of inference of causality from observational data approaching this by network analysis.
The Leid laboratory is primarily focused on the in vivo role of the transcriptional regulatory protein known as Ctip2/Bcl11b. The laboratory discovered the protein and cloned the corresponding cDNA in 2000. The Leid group subsequently defined the molecular and cellular basis for the activity of this transcription factor and demonstrated that the protein plays key roles in the development of several organ systems. The latter studies were conducted using a mouse that was conditionally null for Ctip2/Bcl11b expression, which was created in collaboration with the group of Daniel Metzger (IGBMC, Illkirch, France). Working collaboratively with the Kioussi (OSU), Indra (OSU), Kastner (IGBMC, Illkirch, France), and Rothenberg (Caltech) laboratories, the Leid laboratory has used these mice to demonstrate a crucial role for Ctip2/Bcl11b in development of teeth, skin, and T lymphocytes.