A5085391295- Mitochondrial Function and Pathology
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Fungal and yeast genetics research
- Metabolism and Genetic Disorders
- Force Microscopy Techniques and Applications
- T-cell and B-cell Immunology
- Angiogenesis and VEGF in Cancer
- Monoclonal and Polyclonal Antibodies Research
- Aquaculture Nutrition and Growth
- 3D Printing in Biomedical Research
- CAR-T cell therapy research
- Chronic Kidney Disease and Diabetes
- Gene Regulatory Network Analysis
- Lysosomal Storage Disorders Research
- Viral Infectious Diseases and Gene Expression in Insects
- Photodynamic Therapy Research Studies
- Atherosclerosis and Cardiovascular Diseases
- Enzyme Structure and Function
- Fatty Acid Research and Health
- PI3K/AKT/mTOR signaling in cancer
- Immune Cell Function and Interaction
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Nanoplatforms for cancer theranostics
Central Michigan University
2024-2025
The University of Texas Health Science Center at Houston
2022-2024
The University of Texas MD Anderson Cancer Center
2023-2024
Boston Children's Hospital
2014-2018
Harvard University
2014-2018
Marine Biological Laboratory
2016-2017
Health First
2014
University of California, Irvine
2004-2012
Seoul National University
2012
Beth Israel Deaconess Medical Center
2005
Significance Integrins are adhesion receptors linking cells to their environment, which function as sensors of physical and chemical information regulate development, immune response, vascular function. How integrins receive transduce directional forces including flow or tissue tension has remained elusive. We used polarization-based microscopy techniques discover that activated αVβ3 aligned with one another in focal adhesions migrating fibroblasts. Integrin coalignment is sensitive...
Abstract Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for migration. Here, we test whether the integrin, when engaged to an extracellular ligand and cytoskeleton, adopts a specific orientation dictated by direction of actin flow on migrating cells. We insert GFP into rigid, ligand-binding head model with Rosetta its transition dipole relative integrin head, measure fluorescence polarization microscopy. Cytoskeleton ligand-bound integrins...
Abstract The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, role nature impaired ETC in kidney diseases remains poorly understood. Here, we generate diabetic mice podocyte-specific overexpression Ndufs4, an accessory subunit complex I, as model investigate integrity disease (DKD). We find that conditional male genetic Ndufs4 exhibit...
Projecting or moving up a chemical gradient is universal behavior of living organisms. We tested the ability S. cerevisiaea-cells to sense and respond spatial gradients mating pheromone alpha-factor produced in microfluidics chamber; focus was on bar1Delta strains, which do not degrade input. The yeast cells exhibited good accuracy with projection typically pointing correct direction ( approximately 80% under certain conditions), excellent sensitivity shallow gradients, broad dynamic range...
We use super-resolution interferometric photoactivation and localization microscopy (iPALM) a constrained photoactivatable fluorescent protein integrin fusion to measure the displacement of head lymphocyte function-associated 1 (LFA-1) resulting from conformational change on cell surface. demonstrate that distance LFA-1 increases substantially between basal ligand-engaged conformations, which can only be explained at molecular level by extension. further one class antagonist maintains bent...
Abstract Phenotypic plasticity allows organisms to adapt changing environments within their lifetimes. The cost of plastic adaptations may constrain the persistence over evolutionary time. One potential is possibility that phenotypic adjustment specific can cause correlated responses are not necessarily adaptive. Males in African cichlid Astatotilapia burtoni blue or yellow, and males able adjust body coloration color background, presumably increase crypsis. To test whether background...
The nuclear pore complex (NPC) comprises more than 30 nucleoporins (NUPs) and is a hallmark of eukaryotes. NUPs have been suggested to be important in regulating gene transcription 3D genome organization. However, evidence support their direct roles remains limited. Here, by Cut&Run, we find that core display broad but also cell-type-specific association with active promoters enhancers human cells. Auxin-mediated rapid depletion two demonstrates NUP93, not NUP35, directly specifically...
Yeast cells polarize by projecting up mating pheromone gradients, a classic cell polarity behavior. However, these chemical gradients may shift direction. We examine how yeast sense and respond to 180 o switch in the direction of microfluidically generated gradients. identify two behaviors: at low concentrations α-factor, initial projection grows bending, whereas high concentrations, form second toward new source. Mutations that increase heterotrimeric G-protein activity expand...
Polarized cell morphogenesis requires actin cytoskeleton rearrangement for polarized transport of proteins, organelles and secretory vesicles, which fundamentally underlies differentiation behavior. During yeast mating, Saccharomyces cerevisiae responds to extracellular pheromone gradients by extending projections, are likely maintained through vesicle (exocytosis) from (endocytosis) the membrane. We experimentally demonstrate that projection morphology is concentration‐dependent, propose...
The mitochondrial permeability transition pore (mPTP) is a supramolecular channel that regulates exchange of solutes across cristae membranes, with executive roles in function and cell death. contribution the mPTP to normal physiology remains debated, although evidence implicates inner membrane remodeling differentiating progenitor cells. Here, we demonstrate strict control over conductance shapes metabolic machinery as cells transit toward hematopoietic identity. Cells undergoing...
Social stress can increase reactive oxygen species and derail antioxidant function in the brain, which may contribute to onset progression of mental health disorders. In hierarchical species, repeated social defeat raise oxidative brain. However, how balance brain is regulated across different levels a hierarchy unknown. Here, we study effect status on patterns several divisions highly cichlid fish,
Phosphoinositide 3-kinase (PI3K) is a ubiquitously expressed signaling enzyme that plays an integral role in development and activation of B cells. cell receptor (BCR)-driven proliferation completely blocked either cells lacking the p85alpha regulatory isoform PI3K or wild-type treated with pharmacological inhibitors. However, contribution to early events has not been fully investigated. Here we show have impairments are both quantitatively qualitatively different from those Loss results...
Integrins are transmembrane receptors that, upon activation, bind extracellular matrix (ECM) or cell surface ligands and link them to the actin cytoskeleton mediate adhesion migration 1,2 . One model for structural transitions mediating integrin activation termed “the cytoskeletal force hypothesis” posits that transmitted from ligand-bound integrins acts as an allosteric stabilizer of extended-open, high-affinity state 3 Since forces in migrating cells generated by centripetal “retrograde...
Abstract The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, role nature impaired ETC in kidney diseases remains poorly understood. Here, we generated diabetic mice podocyte-specific overexpression Ndufs4, an accessory subunit complex I, as model investigate integrity disease (DKD). We find that these conditional exhibit significant...
Abstract Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for migration. Here, we test whether the integrin head, known from crystal structures, adopts a specific orientation dictated by direction of actin flow on migrating cells. We insert GFP into rigid head full integrin, model with Rosetta and its transition dipole relative to measure fluorescence polarization microscopy. Dependent coupling cytoskeleton, integrins orient in same as...
SUMMARY Rates of lactate production and consumption reflect the metabolic state many cell types, including neurons. Here, we investigate effects nutrient deprivation on dynamics in Drosophila glutamatergic neurons by leveraging limiting diffusion barrier surrounding cells culture. We found that constitutively consume when availability trehalose, glucose disaccharide preferred insects, is limited barrier. Acute mechanical disruption reduced this reliance lactate. Through kinetic modeling...
Hematopoietic stem cells (HSCs) replenish the blood and immune systems throughout life. Transplantation of HSCs is standard-of-care for patients with bone marrow failure hematological malignancy, yet two-thirds all needing a cell transplant have no suitable donor. This substantial unmet need has driven enterprising efforts to understand manipulate cues that shape HSC specification self-renewal such alternative sources can be generated in dish. The present study was designed contribution...
Abstract Mucopolysaccharidoses (MPS) are lysosomal storage diseases caused by defects in catabolism of glycosaminoglycans. MPS I, II, III and VII associated with accumulation heparan sulphate manifest neurological deterioration. Most these currently lack effective treatments. Here, we report that, compared to controls, neuraminidase 1 (NEU1) activity is drastically reduced brain tissues patients mouse models IIIA, IIIB IIIC, but not other disorders presenting storage. We further show that...