A5034315770- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Nerve injury and regeneration
- Wound Healing and Treatments
- Axon Guidance and Neuronal Signaling
- Planarian Biology and Electrostimulation
- Cellular Mechanics and Interactions
- Autophagy in Disease and Therapy
- Adipose Tissue and Metabolism
- Inflammatory Myopathies and Dermatomyositis
- Redox biology and oxidative stress
- Connexins and lens biology
- Urologic and reproductive health conditions
- Glycosylation and Glycoproteins Research
- ATP Synthase and ATPases Research
- Pancreatic and Hepatic Oncology Research
- Burn Injury Management and Outcomes
- Photoreceptor and optogenetics research
- Cellular transport and secretion
- Marine Invertebrate Physiology and Ecology
- Galectins and Cancer Biology
- Cancer Immunotherapy and Biomarkers
- Nuclear Structure and Function
- Biochemical effects in animals
- Extracellular vesicles in disease
University of Wisconsin–Madison
2023-2025
Children's National
2016-2020
George Washington University
2017-2019
University of Nebraska Medical Center
2012-2014
Mitochondria transduce the cytosolic Ca 2+ increase caused by plasma membrane injury into a ROS-dependent repair response.
Dystrophin deficiency is the genetic basis for Duchenne muscular dystrophy (DMD), but cellular of progressive myofiber death in DMD not fully understood. Using two dystrophin-deficient mdx mouse models, we find that mitochondrial dysfunction among earliest deficits muscles. Mitochondria dystrophic myofibers also respond poorly to sarcolemmal injury. These reduce ability muscle cell membranes repair and are associated with a compensatory increase dysferlin-mediated membrane proteins....
Muscle function is regulated by Ca2+, which mediates excitation-contraction coupling, energy metabolism, adaptation to exercise, and sarcolemmal repair. Several of these actions rely on Ca2+ delivery the mitochondrial matrix via uniporter, pore formed calcium uniporter (MCU). MCU's gatekeeping cooperative activation are controlled MICU1. Loss-of-protein mutation in MICU1 causes a neuromuscular disease. To determine mechanisms underlying muscle impairments, we used patient cells skeletal...
Plasma membrane injury can cause lethal influx of calcium, but cells survive by mounting a polarized repair response targeted to the wound site. Mitochondrial signaling within seconds after enables this response. However, as mitochondria are distributed throughout cell in an interconnected network, it is unclear how they generate spatially restricted signal plasma wound. Here we show that calcium and Drp1-mediated, rapid mitochondrial fission at site help polarize Fission injury-proximal...
Amoeboid cells like leukocytes can enter and migrate in diverse tissues, even though tissues vary widely their chemical mechanical composition. Here, we imaged motile T as they colonized peripheral during zebrafish development to ask if tailor migration strategy local tissue environment. We found that most sites migrated with F-actin-rich leading-edge pseudopods, matching how vitro. notably deviated from this the epidermis, where instead using a rearward concentration of F-actin stable...
Abstract Leukocytes forge paths through interstitial spaces by exerting forces to overcome confining mechanical pressures provided surrounding cells. While such cues regulate leukocyte motility, engineering an in vitro system that models the deformable cellular environment encountered vivo has been challenging. Here, microchannels are constructed with a liquid‐liquid interface exerts similar cells tissues, and thus, is cell‐generated forces. Consequently, balance between migratory...
ABSTRACT Secondary fungal infections represent a major complication following thermal injuries. However, the mechanisms of colonization burn tissue and how host subsequently responds to fungi within this niche remain unclear. We have previously reported zebrafish model injury that recapitulates many features human wounds. Here, we characterize host-fungal interaction dynamics wound using two most common pathogens isolated from injuries, Aspergillus fumigatus Candida albicans . Both A. C....
Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed various malignancies. We others shown that MUC1 MUC4, two mucins, play a sentinel role cell signaling events drive several epithelial In the present study, we investigated profile MUC4 non-neoplastic bladder urothelium, malignant neoplasms carcinoma lines.Immunohistochemistry was performed on tissue sections from urinary biopsies, resection samples microarrays (TMAs) with monoclonal...
The use of virtual microscopy (VM) in clinical cytology has been limited due to the inability focus through three dimensional (3D) cell clusters with a single focal plane (2D images). Limited information exists regarding optimal scanning parameters for 3D scanning.The purpose this study was determine number levels and interval digitize gynecological (GYN) specimens prepared on SurePath™ glass slides while maintaining manageable file size.The iScanCoreo Au scanner (Ventana, AZ, USA) used 192...
Abstract The etiology of myositis is unknown. Although attempts to identify viruses in skeletal muscle have failed, several studies identified the presence a viral signature patients. Here we postulate that individuals with susceptible genetic backgrounds, infection alters epigenome activate pathological pathways leading disease onset. To epigenetic changes, methylation profiling Coxsackie B infected human myotubes and biopsies from polymyositis (PM) dermatomyositis (DM) patients were...
A hitherto undescribed phenotype of early onset muscular dystrophy associated with sensorineural hearing loss and primary ovarian insufficiency was initially identified in 2 siblings subsequent patients a similar constellation findings. The goal this study to understand the genetic molecular etiology condition.
Epithelial damage leads to early reactive oxygen species (ROS) signaling, which regulates sensory neuron regeneration and tissue repair. How the initial type of injury influences signaling regenerative growth axons remains unclear. Previously we reported that thermal triggers distinct responses in larval zebrafish. Here, found but not mechanical impairs axon function. Real-time imaging revealed an immediate response characterized by rapid Arp2/3-dependent migration keratinocytes, was...
Context.—Diagnoses rendered as atypical/suspicious for malignancy on fine-needle aspiration (FNA) of pancreatic mass lesions range from 2% to 29% in various studies. We have identified the expression 3 genes, MUC4, MUC16, and NGAL that are highly upregulated adenocarcinoma. In this study, we analyzed these markers FNA samples determine whether they could improve sensitivity specificity. Objective.—To evaluate utility evaluation specimens. Design.—Records FNAs performed during 10 consecutive...
Epithelial damage leads to early reactive oxygen species (ROS) signaling, which regulates sensory neuron regeneration and tissue repair. How the initial type of injury influences signaling regenerative growth axons remains unclear. Previously we reported that thermal triggers distinct responses in larval zebrafish. Here, found but not mechanical impairs axon function. Real-time imaging revealed an immediate response characterized by rapid Arp2/3-dependent migration keratinocytes, was...
Deficits in plasma membrane repair have been identified dysferlinopathy and Duchenne Muscular Dystrophy, contribute to progressive myopathy. Although Facioscapulohumeral Dystrophy (FSHD) shares clinicopathological features with these muscular dystrophies, it is unknown if FSHD characterized by deficits. Therefore, we exposed immortalized human myoblasts, myoblasts from unaffected siblings, myofibers a murine model of (FLExDUX4) focal, pulsed laser ablation the sarcolemma. Repair kinetics...
Abstract Burn injuries undergo a complex healing process in which progressive spreading of epithelial damage can lead to secondary complications such as wound infection, is major driver mortality among burn patients. We recently reported that burning larval zebrafish triggers dysregulated keratinocyte dynamics compared mechanical injury. Here, we investigate behavior following injury and the subsequent potential for microbial colonization wounds over time. Real-time imaging, coupled with...
Burn injuries undergo a complex healing process in which progressive spreading of epithelial damage can lead to secondary complications such as wound infection, is major driver mortality among burn patients. We recently reported that burning larval zebrafish triggers dysregulated keratinocyte dynamics compared mechanical injury. Here, we investigate behaviour following injury and the subsequent potential for microbial colonisation wounds over time. Real-time imaging, coupled with tracking...
One of the drawbacks studying pathology in second year medical school a classroom setting is relatively limited exposure to patient encounters/clinical rotations, making it difficult understand and fully appreciate significance course material, specifically molecular tissue aspects disease. In this study, we determined if case vignettes incorporating pathologist-clinician encounters with whole slide imaging (WSI) narrated/annotated videos (WS) scans addition clinical data improved student...
Tumors-to-tumor metastasis is an uncommon occurrence and can be a source of great diagnostic difficulty, especially when the donor tumor undiagnosed. Here we report case kidney resected for primary neoplasm (oncocytoma) that harbored metastases from clinically undiagnosed prostatic adenocarcinoma. The presence poorly differentiated within otherwise typical oncocytoma in absence surrounding nonneoplastic renal parenchyma resulted dilemma. To our knowledge, this first English literature...
Desmoid tumors are rare soft-tissue masses originating from the proliferation of fibroblasts in fibroconnective tissues. Intra-abdominal desmoid pose special diagnostic challenge due to multiplicity differential diagnoses, and difficulty well characterize lesions on imaging studies. can have atypical presentation making clinical correlation challenging unsuspecting urologists. Only a few cases been reported urology literature. In this report, we present case tumor presenting with gross hematuria.
Leukocytes navigate through interstitial spaces resulting in deformation of both the motile leukocytes and surrounding cells. Creating an vitro system that models deformable cellular environment encountered vivo has been challenging. Here, we engineer microchannels with a liquid-liquid interface exerts confining pressures (200-3000 Pa) similar to cells tissues, and, thus, is by cell generated forces. Consequently, balance between migratory cell-generated interfacial determines degree...
Abstract Introduction Larval zebrafish have been widely adopted as a model to study tissue repair and regeneration. Due their optical transparency, larval are amenable live imaging, which enables real-time investigation of early dynamics following injury. Here, we utilized previously developed method burning investigate how epithelial responds We find that aberrant keratinocyte signaling contribute long-term damage in burn wounded tissue, but treatment with isotonic medium limited overall by...