A5028054127- Acute Myeloid Leukemia Research
- Pluripotent Stem Cells Research
- Liver physiology and pathology
- Erythrocyte Function and Pathophysiology
- Lymphoma Diagnosis and Treatment
- Heme Oxygenase-1 and Carbon Monoxide
- Cell Adhesion Molecules Research
- Mesenchymal stem cell research
- Porphyrin Metabolism and Disorders
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Cerebrospinal fluid and hydrocephalus
- Cancer-related gene regulation
- Hemoglobin structure and function
- Traumatic Brain Injury and Neurovascular Disturbances
- Blood properties and coagulation
- RNA Research and Splicing
- Cellular Mechanics and Interactions
- Tissue Engineering and Regenerative Medicine
- Fibroblast Growth Factor Research
- PI3K/AKT/mTOR signaling in cancer
- Electrochemical sensors and biosensors
- Intraocular Surgery and Lenses
- Developmental Biology and Gene Regulation
- T-cell and Retrovirus Studies
Van Andel Institute
2007-2022
Biotechnology Institute
2021-2022
University of Delaware
2020-2021
Case Western Reserve University
2011
Western Michigan University
2011
Helen DeVos Children's Hospital
2006-2007
Corewell Health Blodgett Hospital
2006-2007
Spectrum Health
2004-2007
Canonical Wnt signals are transduced through a Frizzled receptor and either the LRP5 or LRP6 co-receptor; such play central roles during development in disease. We have previously shown that Lrp5 is required for ductal stem cell activity loss of delays normal mammary Wnt1-induced tumorigenesis. Here we show canonical Lrp6 co-receptor also mouse gland development. Loss compromises Wnt/beta-catenin signaling interferes with placode, fat pad, branching embryogenesis. Heterozygosity an...
Activated T cells rapidly assemble filamentous (F-) actin networks in response to ligation of the cell receptor or upon interaction with adhesive stimuli order facilitate migration and formation immune synapse. Branched filament assembly is crucial for this process dependent activation Arp2/3 complex by nucleation-promoting factor Wiskott-Aldrich Syndrome protein (WASp). Genetic disruption WAS gene has been linked hematopoietic malignancies various cytopenias. Although contributions WASp...
Abstract Rho GTPase-effector mammalian diaphanous (mDia)–related formins assemble nonbranched actin filaments as part of cellular processes, including cell division, filopodia assembly, and intracellular trafficking. Whereas recent efforts have led to thorough characterization in cytoskeletal remodeling assembly vitro, little is known about the role mDia proteins vivo. To fill this knowledge gap, Drf1 gene, which encodes canonical formin mDia1, was targeted by homologous recombination. Upon...
Abstract The hepatocyte growth factor (HGF)-MET pathway supports several hallmark cancer traits, and it is frequently activated in a broad spectrum of human cancers (http://www.vai.org/met/). With the development many drugs targeting this pathway, there need for relevant vivo model systems preclinical evaluation drug efficacy. Here, we show that production HGF ligand transgenic severe combined immunodeficient mice (hHGFtg-SCID mice) enhances MET-expressing carcinoma xenografts, including...
Bone marrow (BM) is an excellent source of mesenchymal stem cells (MSC) which can be expanded in vitro for further use. However, large volumes BM specimens are not routinely available. We hypothesized that the normally discarded collection kits might a convenient numbers MSC.Marrow were isolated from used Fenwal kits. Purified mononuclear (MNC) screened by multiparameter flow cytometry to identify MSC, later culture. Immunophenotyping and differentiation assays performed initially at...
Heme plays a critical role in catalyzing life-essential redox reactions all cells, and its synthesis must be tightly balanced with cellular requirements. eukaryotes is regulated by the mitochondrial AAA+ unfoldase CLPX (caseinolytic matrix peptidase chaperone subunit X), which promotes heme activation of δ-aminolevulinate synthase (ALAS/Hem1) yeast regulates turnover ALAS1 human cells. However, specific mechanisms are unclear. In this study, we interrogated erythroid Quantitation enzyme...
The inappropriate expression of the c-MET cell surface receptor in many human solid tumors necessitates development companion diagnostics to identify those patients who could benefit from targeted therapies. Tumor tissues are formalin fixed and paraffin embedded (FFPE) for histopathologic evaluation, making an antibody against that accurately reproducibly detects protein FFPE samples urgent need. We have developed a monoclonal (mAb), designated MET4, panel MET-avid mAbs, based on its...
Abstract While silicone devices have vastly improved an array of medical treatments, reactions at the tissue‐substrate interface often impede their functionality. Insertion a poly(dimethyl)siloxane (PDMS) catheter into cerebral ventricles to drain excess cerebrospinal fluid (CSF) is most common treatment hydrocephalus, but shunting fails because inflammatory tissue, choroid plexus cells, and debris grow these central nervous system catheters obstruct flow. We hypothesized that plasma...
Abstract Cellular obstruction of poly(dimethyl)siloxane (PDMS) catheters is one the most prevalent causes shunt failure in treatment hydrocephalus. By modifying PDMS using short‐ and long‐chain mono‐functional polyethylene glycol (PEG604 PEG5K, respectively) N ‐acetyl‐ L ‐cysteine via adsorption covalent binding (NAC NAC/EDC/NHS, respectively), we increased surface wettability. We hypothesized that these modifications would inhibit protein decrease host macrophage astrocyte adhesion. Tested...
Myelodysplastic syndrome (MDS) is characterized by ineffective hematopoiesis and hyperplastic bone marrow. Complete loss or interstitial deletions of the long arm chromosome 5 occur frequently in MDS. One candidate tumor suppressor on 5q mammalian Diaphanous (mDia)-related formin mDia1, encoded DIAPH1 (5q31.3). mDia-family formins act as effectors for Rho-family small GTP-binding proteins including RhoB, which has also been shown to possess activity. Mice lacking Drf1 gene that encodes mDia1...
Human parthenogenetic stem cells (hpSCs) are pluripotent with enormous potential as cell sources for cell-based therapies: hpSCs may have histocompatibilty advantages over human embryonic (hESCs) and derivation of does not require viable blastocyst destruction. For translation all therapies, differentiated products that contaminated undifferentiated is a major technical roadblock. We report here novel method to derive high-purity definitive endoderm (DE) from hpSCs, based on reproducing...
Human parthenogenetic stem cells are derived from the inner cell mass of blastocysts obtained unfertilized oocytes that have been stimulated to develop without any participation male gamete. As parthenogenesis does not involve destruction a viable human embryo, derivation and use raise same ethical concerns as conventional embryonic cells. similar in their proliferation multilineage vitro differentiation capacity. The aim this study is derive multipotent neural stable passaging...
A bienzymatic electrode incorporating trehalase (Tre) and glucose oxidase (GOx) covalently bound to the surface of Pt through a functionalized thiol linker (Tre|GOx|Pt) has been designed assembled its catalytic properties examined by chemical electrochemical methods in aqueous phosphate buffer solutions (PBS, pH 7.4). Exposure Tre|GOx|Pt PBS containing trehalose (Tr) subsequent polarization at 0.6 V versus Ag/AgCl yielded after few minutes well-defined steady-state currents ascribed...
Perinatal infection with a temperature-sensitive mutant (ts-1) of Moloney murine leukemia virus (MoMuLV) results in massive splenomegaly and thymomegaly mice development lymphoma >55 % infected pups. Previous flow cytometry studies showed decrease CD4(+) cells perinatally pups, but cell population changes animals compared without has not yet been reported. In the current study, BALB/c were ts-1 through breast milk transmission observed until clinical signs symptoms and/or symptomatic...
Erythroid differentiation (ED) is a complex cellular process entailing morphologically distinct maturation stages of erythroblasts during terminal differentiation. Studies actin filament (F-actin) assembly and organization ED have revealed essential roles for the F-actin pointed-end capping proteins, tropomodulins (Tmod1 Tmod3). Tmods bind tropomyosins (Tpms), which enhance Tmod stabilization. can also nucleate assembly, independent Tpms. Tmod1 present in red blood cell (RBC) membrane...
Loss of heterozygosity and promoter hypermethylation APC is frequently observed in human endometrial cancer, which the most common gynecological cancer USA, but its carcinogenic driver status epithelium has not been confirmed. We have identified a novel population progenitor epithelial cells (EECs) mice that express lysozyme M (LysM) give rise to approximately 15% all EECs adult mice. LysM glycoside hydrolase encoded by Lyz2 functions protect from bacteria as part innate immune system. Its...
Abstract Heme is a prosthetic group that plays critical role in catalyzing life-essential redox reactions all cells, including metabolic processes. synthesis must be tightly co-regulated with cellular requirements order to maximize utilization and minimize toxicity. Terminally differentiating erythroid cells have an extremely high demand for heme hemoglobin synthesis. While the enzymatic of are well studied, mechanisms by which mitochondrial homeostatic machinery interacts regulates poorly...