A5055091291- Retinal Development and Disorders
- Mitochondrial Function and Pathology
- Retinal Diseases and Treatments
- Metabolism and Genetic Disorders
- RNA regulation and disease
- Orthopedic Infections and Treatments
- Retinal Imaging and Analysis
- Infectious Diseases and Tuberculosis
- Osteomyelitis and Bone Disorders Research
- CRISPR and Genetic Engineering
- ATP Synthase and ATPases Research
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Adipose Tissue and Metabolism
- Fetal and Pediatric Neurological Disorders
- Lysosomal Storage Disorders Research
- Spinal Dysraphism and Malformations
- Retinoids in leukemia and cellular processes
- Antimicrobial Resistance in Staphylococcus
- Infective Endocarditis Diagnosis and Management
- Autophagy in Disease and Therapy
- Cerebrospinal fluid and hydrocephalus
- Liver Disease Diagnosis and Treatment
- Corneal Surgery and Treatments
- Monoclonal and Polyclonal Antibodies Research
University of Rochester Medical Center
2019-2023
Bowling Green State University
2023
University of Rochester
2011-2021
Applied BioPhysics (United States)
2010
University of Georgia
2009
Mitochondria in mammals are organized into tubular networks that undergo frequent shape change. Mitochondrial fission and fusion the main components mediating mitochondrial Perturbation of fission/fusion balance is associated with many disease conditions. However, underlying mechanisms not well understood. requires dynamin-like protein DLP1/Drp1 recruited to surface, possibly through membrane-anchored Fis1 or Mff. Additional dynamin-related GTPases, mitofusin (Mfn) OPA1, outer inner...
Mitochondria produce the majority of cellular ATP through oxidative phosphorylation, and their capacity to do so is influenced by many factors. Mitochondrial morphology recently suggested as an important contributor in controlling mitochondrial bioenergetics. divide fuse continuously, which affected environmental factors, including metabolic alterations. Underscoring its bioenergetic influence, altered reported tissues patients animal models dysfunction. In this study, we found that fission...
Significance Age-related macular degeneration (AMD) and related dystrophies (MDs) are a major cause of vision loss. However, pharmacological treatments in these diseases limited due to the lack knowledge underlying disease mechanisms, partly because appropriate human models study AMD MDs lacking. Furthermore, living eye, entire retina acts as functional unit, making it difficult investigate specific contribution particular retinal cell type disease. Here, we established multiple MDs, which...
Abstract Perivascular spaces (PVS) drain brain waste metabolites, but their specific flow paths are debated. Meningeal pia mater reportedly forms the outermost boundary that confines around blood vessels. Yet, we show is perforated and permissive to PVS fluid flow. Furthermore, demonstrate comprised of vascular cerebral layers coalesce in variable patterns along leptomeningeal arteries, often merging penetrating arterioles. Heterogeneous pial architectures form sieve-like structures...
Arachnoid granulations (AG) are poorly investigated. Historical reports suggest that they regulate brain volume by passively transporting cerebrospinal fluid (CSF) into dural venous sinuses. Here, we studied the microstructure of cerebral AG in humans with aim understanding their roles physiology. We discovered marked variations size, lobation, location, content, and degree surface encapsulation. High-resolution microscopy shows consist outer capsule inner stromal core regions. The fine...
Mitochondria are the essential eukaryotic organelles that produce most cellular energy. The energy production and supply by mitochondria appear closely associated with continuous shape change of mediated fission fusion, as evidenced not only hereditary diseases caused mutations in fission/fusion genes but also aberrant mitochondrial morphologies numerous pathologic insults. However, how morphological is linked to their energy-producing activity poorly understood. In this study, we found...
Abstract Mitochondria are critical for metabolic homeostasis of the liver, and their dysfunction is a major cause liver diseases. Optic atrophy 1 (OPA1) mitochondrial fusion protein with role in cristae shaping. Disruption OPA1 causes dysfunction. However, function poorly understood. In this study, we delete fully developed male mice. Unexpectedly, knockout (LKO) mice healthy unaffected respiration, despite disrupted morphology. LKO induces stress response that establishes new homeostatic...
Staphylococcus aureus infection of bone is challenging to treat because it colonizes the osteocyte lacuno-canalicular network (OLCN) cortical bone. To elucidate factors involved in OLCN invasion and identify novel drug targets, we completed a hypothesis-driven screen 24 S. transposon insertion mutant strains for their ability propagate through 0.5 μm-sized pores Microfluidic Silicon Membrane Canalicular Arrays (μSiM-CA), developed model OLCN. This identified uncanonical transpeptidase,...
Recombinant mammalian proteins expressed in E. coli can be difficult to purify high yield a soluble and functional form. Various techniques have been described prevent proteolysis of and/or their sequestering as insoluble aggregates within inclusion bodies. We report conditions for expressing recombinant from that significantly enhanced the protein. demonstrate high-yield recovery native, high-molecular-weight RNA binding protein without aid fusion sequence. The principle factor increased...
In typical cultured animal cells, mitochondria exist in shapes ranging from long interconnected tubules, often clustered the perinuclear region of cell, to small spherical forms cell periphery. However, mitochondrial appearance at any given moment time is only a snapshot dynamic
Staphylococcus aureus invasion of the osteocyte lacuno-canalicular network (OLCN) is a novel mechanism bacterial persistence and immune evasion in chronic osteomyelitis. Previous work highlighted S. cell wall transpeptidase, penicillin binding protein 4 (PBP4), surface adhesin, C (SasC), as critical factors for deformation propagation through nanopores vitro , representative confined canaliculi vivo . Given these findings, we hypothesized that synthesis machinery adhesins enable durotaxis-...
Abstract Mutations in CLN3 lead to photoreceptor cell loss disease, a lysosomal storage disorder characterized by childhood-onset vision loss, neurological impairment, and premature death. However, how mutations cause death is not known. Here, we show that required for phagocytosis of outer segment (POS) retinal pigment epithelium (RPE) cells, cellular process essential survival. Specifically, proportion human, mouse, iPSC-RPE cells localized RPE microvilli, the site POS phagocytosis....
We have previously reported a positive correlation between the expression of BHMT (betaine–homocysteine S-methyltransferase) and ApoB (apolipoprotein B) in rat hepatoma McA (McArdle RH-7777) cells [Sowden, Collins, Smith, Garrow, Sparks (1999) Biochem. J. 341, 639–645]. To examine whether similar relationship occurs vivo, hepatic was induced by feeding rats Met (L-methionine)-restricted betaine-containing diet, parameters metabolism were evaluated. There no generalized metabolic...
Purpose: RPE cell transplantation as a potential treatment for AMD has been extensively investigated; however, in AMD, ultrastructural damage affects both the and its underlying matrix support, Bruch's membrane (BrM). An monolayer supported by surrogate scaffold could thus provide more effective approach to cell-based therapy AMD. Toward this goal, we aimed establish functional human induced pluripotent stem cell–derived (hiPSC)-RPE on Bombyx mori silk fibroin (BMSF) scaffold. Methods:...
Retinal pigment epithelium (RPE) cell dysfunction is central to the pathogenesis of age-related macular degeneration (AMD), a leading cause adult blindness. Aging, single biggest risk factor for AMD development, favors increase in RPE autofluorescent material due accumulation POS-digestion by-products through lysosomal and impaired POS degradation. Apart from aging, environmental agents affect function multiple model systems are implicated AMD. Iron (Fe) overload cigarette smoke exposure two...
Abstract Osteomyelitis is a devastating complication of orthopaedic surgery and commonly caused by Staphylococcus aureus ( S. ) Group B Streptococcus (GBS, agalactiae ). Clinically, osteomyelitis associated with local inflammation, abscesses, aggressive osteolysis, septic implant loosening. In contrast, infections generally involve soft tissue, acute life‐threatening vascular spread. While preclinical models that recapitulate the clinical features bone infection have proven useful for...
S. aureus infection of bone is difficult to eradicate due its ability colonize the osteocyte-lacuno-canalicular network (OLCN), rendering it resistant standard-of-care (SOC) antibiotics. To overcome this, we proposed two bone-targeted bisphosphonate-conjugated antibiotics (BCA): sitafloxacin (BCS) and hydroxybisphosphonate-conjugate (HBCS). Initial studies demonstrated that BCA kills in vitro . Here demonstrate vivo efficacy BCS HBCS versus bisphosphonate, sitafloxacin, vancomycin mice with...