A5101645127- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Renal and related cancers
- Reproductive Biology and Fertility
- Biomedical Ethics and Regulation
- 3D Printing in Biomedical Research
- Genetics, Aging, and Longevity in Model Organisms
- Neuroscience and Neural Engineering
- RNA modifications and cancer
- Advanced Fluorescence Microscopy Techniques
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Single-cell and spatial transcriptomics
- RNA Interference and Gene Delivery
- Chromosomal and Genetic Variations
- Fungal and yeast genetics research
- Tissue Engineering and Regenerative Medicine
- DNA Repair Mechanisms
- RNA Research and Splicing
- Protein Tyrosine Phosphatases
- Zebrafish Biomedical Research Applications
- Acute Myeloid Leukemia Research
University of California, Irvine
2010-2024
UC Irvine Health
2016
University of Pennsylvania
2003-2009
Johns Hopkins University
1998-2008
Johns Hopkins Medicine
1999-2008
Harvard Stem Cell Institute
2004-2006
Thomas Jefferson University
1998-2003
Sidney Kimmel Cancer Center
1999-2003
South University
2003
Scripps Research Institute
2003
Human pluripotent stem cells would be invaluable for in vitro studies of aspects human embryogenesis. With the goal establishing cell lines, gonadal ridges and mesenteries containing primordial germ (PGCs, 5–9 weeks postfertilization) were cultured on mouse STO fibroblast feeder layers presence recombinant leukemia inhibitory factor, basic growth forskolin. Initially, single PGCs culture visualized by alkaline phosphatase activity staining. Over a period 7–21 days, gave rise to large...
We describe a label-free imaging method to monitor stem-cell metabolism that discriminates different states of stem cells as they differentiate in living tissues. In this we use intrinsic fluorescence biomarkers and the phasor approach lifetime microscopy conjunction with image segmentation, which introduce concept cell phasor. live tissues are able identify fluorophores, such collagen, retinol, retinoic acid, porphyrin, flavins, free bound NADH. have exploited detect trend metabolite...
We used a panel of human and mouse fibroblasts with various abilities for supporting the prolonged growth embryonic stem cells (hESCs) to elucidate factors required hESC survival, proliferation, maintenance undifferentiated pluripotent state (self‐renewal). found that supportive feeder secrete both survival/proliferation blocking spontaneous differentiation achieve self‐renewal. The antidifferentiation soluble factor is neither leukemia inhibitory nor Wnt, based on experiments using their...
Abstract Human embryonic stem (hES) cells, derived from blastocysts, are capable of unlimited self-renewal and differentiation into all cell lineages the body. Because their pluripotent nature, hES cells valuable tools for understanding human development advancing field regenerative medicine. However, one key to harnessing therapeutic power biomedical applications begins with determining how these maintain undifferentiated state. Studies in mice have implicated three factors regulating...
There is a lack of fast and high resolution methods to measure metabolic activity single cells in their native environment. Here we develop straightforward, non-invasive sensitive method phenotype live tissue. By using NADH as optical biomarker the phasor approach Fluorescence Lifetime microscopy (FLIM) identify cellular fingerprints related different rates oxidative phosphorylation glycolysis. For first time three dimensional gradient small intestine (SI) epithelia that appears tightly...
An emerging family of kinases related to the Drosophila Aurora and budding yeast Ipl1 proteins has been implicated in chromosome segregation mitotic spindle formation a number organisms. Unlike other Aurora/Ipl1-related kinases, Caenorhabditis elegans orthologue, AIR-2, is associated with meiotic chromosomes. AIR-2 initially localized chromosomes most mature prophase I–arrested oocyte residing next spermatheca. This localization dependent on presence sperm After fertilization, remains during...
Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscular in which no mutation of pathogenic gene(s) has been identified. Instead, the disease is, most cases, genetically linked to a contraction number 3.3 kb D4Z4 repeats on chromosome 4q. How 4qter causes not understood. In addition, smaller group FSHD cases are associated with repeat (termed "phenotypic" FSHD), and their etiology remains undefined. We carried out chromatin immunoprecipitation analysis using D4Z4-specific PCR...
S. cerevisiae Ipl1, Drosophila Aurora, and the mammalian centrosomal protein IAK-1 define a new subfamily of serine/threonine kinases that regulate chromosome segregation mitotic spindle dynamics. Mutations in ipl1 aurora result generation severely aneuploid cells and, case aurora, monopolar spindles arising from failure centrosome separation. Here we show related, essential C. elegans, AIR-1 (Aurora/Ipl1 related), is localized to centrosomes. Disruption expression elegans embryos results...
Establishment of the mammalian germ line is a prerequisite for fertility adult animal but we know surprisingly little about molecular mechanisms regulating germ-line development in mammals. Signaling from c-Kit receptor tyrosine kinase essential primordial cell (PGC) growth both vivo and vitro . Many downstream effectors signaling pathway have been identified other types how these molecules control PGC survival proliferation are unknown. Determination acting PGCs has hampered by lack...
The Cdc25 family of protein phosphatases positively regulates cell division by activating cyclin-dependent kinases (CDKs).In humans and rodents, there are three members-denoted Cdc25A, Cdc25B, Cdc25C-that can be distinguished based on their subcellular compartmentalizations, abundances and/or activities throughout the cycle, CDKs that they target for activation, whether overexpressed in human cancers.In addition, murine forms exhibit distinct patterns expression development adult...
The Steel (Sl) locus is essential for the development of germ cells, hematopoietic and melanocytes encodes a growth factor (Mgf) that ligand c-kit, receptor tyrosine kinase encoded by W locus. We have identified molecular cell defects in two mutant Sl alleles, Steel-panda (Slpan) Steel-contrasted (Slcon), cause sterility only females. Unexpectedly, both alleles are shown to contain DNA rearrangements, located > 100 kb 5' Mgf-coding sequences, lead tissue-specific effects on Mgf mRNA...
We describe a novel mammalian protein kinase related to two newly identified yeast and fly kinases—Ipl1 aurora, respectively—mutations in which cause disruption of chromosome segregation. have designated this as Ipl1- aurora-related 1 (IAK1). IAK1 expression mouse fibroblasts is tightly regulated temporally spatially during the cell cycle. Transcripts first appear at G1/S boundary, are elevated M-phase, disappear rapidly after completion mitosis. The levels activity also cycle with peak...
The murine dominant White spotting (W) and Steel (Sl) loci encode the c-kit tyrosine kinase receptor its cognate ligand steel factor (SLF), respectively. Mutations at either locus produce deficiencies in same three migratory cell populations--those giving rise to pigment cells, germ blood cells. identification of gene products these two combined with plethora W Sl mutations available for molecular analysis offers a unique opportunity dissect role during development fashion not possible most...
RAD51C is a member of the RecA/RAD51 protein family, which known to play an important role in DNA repair by homologous recombination. In mice, it essential for viability. Therefore, we have generated hypomorphic allele Rad51c addition null allele. A subset mice expressing infertile. This infertility caused sexually dimorphic defects meiotic recombination, revealing its two distinct functions. Spermatocytes undergo developmental arrest during early stages prophase I, providing evidence...
Cranial irradiation remains a frontline treatment for the control of tumor growth, and individuals surviving such treatments often manifest various degrees cognitive dysfunction. Radiation-induced depletion stem/precursor cell pools in brain, particularly those residing neurogenic region hippocampus, is believed, part, to be responsible these often-unavoidable deficits. To explore possibility ameliorating radiation-induced impairment, athymic nude rats subjected head only (10 Gy) were...