- Protease and Inhibitor Mechanisms
- Retinal Imaging and Analysis
- Peptidase Inhibition and Analysis
- Bone fractures and treatments
- Cell Adhesion Molecules Research
- Glaucoma and retinal disorders
- Spine and Intervertebral Disc Pathology
- Enzyme Production and Characterization
- Spinal Fractures and Fixation Techniques
- Brain Tumor Detection and Classification
- Medical Image Segmentation Techniques
- Head and Neck Surgical Oncology
- Retinal Diseases and Treatments
- Mesenchymal stem cell research
- Optical Coherence Tomography Applications
- Chromatin Remodeling and Cancer
- Prenatal Substance Exposure Effects
- Bone and Joint Diseases
- Phosphodiesterase function and regulation
- Amoebic Infections and Treatments
- Cancer therapeutics and mechanisms
- Glioma Diagnosis and Treatment
- Hematological disorders and diagnostics
- Homelessness and Social Issues
- Amyotrophic Lateral Sclerosis Research
Massachusetts Institute of Technology
2020-2023
Carl Zeiss (United States)
2020-2021
Biogen (United States)
2018
Cedars-Sinai Medical Center
2011-2015
California Institute for Regenerative Medicine
2013
University of Southern California
2003
University of Louisville
1999-2002
University of Minnesota
1988
Vertebral compression fractures (VCFs), the most common fragility fractures, account for approximately 700,000 injuries per year. Since open surgery involves morbidity and implant failure in osteoporotic patient population, a new minimally invasive biological solution to vertebral bone repair is needed. Previously, we showed that adipose-derived stem cells (ASCs) overexpressing BMP gene are capable of inducing spinal fusion vivo. We hypothesized direct injection ASCs, designed transiently...
Diverse processes in cancer are mediated by enzymes, which most proximally exert their function through activity. High-fidelity methods to profile enzyme activity therefore critical understanding and targeting the pathological roles of enzymes cancer. Here, we present an integrated set for measuring specific protease activities across scales, deploy these study treatment response autochthonous model Alk-mutant lung We leverage multiplexed nanosensors machine learning analyze vivo dynamics...
Osteoporosis affects more than 200 million people worldwide leading to 2 fractures in the United States alone. Unfortunately, surgical treatment is limited patients with low bone mass. Parathyroid hormone (PTH) was shown induce fracture repair animals by activating mesenchymal stem cells (MSCs). However, it would be less effective fewer and/or dysfunctional MSCs due aging and comorbidities. To address this, we evaluated efficacy of combination i.v. MSC PTH therapy versus monotherapy...
AbstractUpregulation of the cAMP/protein kinase A (PKA) pathway has been shown to result in decreased proliferation, increased differentiation, and subsequent apoptosis malignant glioma cells. Conventional cAMP analogs, however, are difficult use a clinical setting. Therefore, we investigated effects rolipram, drug that undergone trials as an antidepressant also proposed treatment for multiple sclerosis. Rolipram acts specific inhibitor type IV phosphodiesterase (PDE4), leading intracellular...
Osteoporotic patients, incapacitated due to vertebral compression fractures (VCF), suffer grave financial and clinical burden. Current treatments focus on symptoms’ management but do not combat the issue at source. In this pilot study, allogeneic, porcine mesenchymal stem cells, overexpressing BMP6 gene (MSC‐BMP6), were suspended in fibrin gel implanted into a defect investigate their effect bone regeneration clinically relevant, large animal pig model. To check of BMP6‐modified cells...
Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting allograft osseointegration cranial membranous bones. Calvarial defects were created transgenic mice, which luciferase is expressed under control osteocalcin promoter. The mice given implants allografts or without daily PTH...
The topoisomerase-I inhibitor irinotecan (CPT-11) is currently used in Phase I/II trials for the treatment of patients with recurrent malignant gliomas. Protein kinase C (PKC) inhibitors such as high-dose tamoxifen and hypericin also have been current study examined role PKC chemosensitizers CPT-11 their proposed mechanism action. Two glioma cell lines (A-172 U-87) one primary culture (LA-567) were used. Proliferation ((3)H-thymidine) cytotoxicity (methylthiotetrazole) studies performed...
The use of multicomponent scaffolds for cell implantation has necessitated sophisticated techniques tracking survival in vivo. Bioluminescent imaging (BLI) emerged as a noninvasive tool evaluating the therapeutic potential cell-based tissue engineering strategies. However, ability to BLI measurements longitudinally assess large 3D cellular constructs vivo and effects confounding factors are poorly understood. In this study, luciferase-expressing human mesenchymal stem cells (hMSCs) were...
✓ Although most meningiomas are treated surgically, it may not be possible to completely remove atypical, malignant, and surgically inaccessible meningiomas; in the majority of these cases there is tumor recurrence. The authors have already reported initial preclinical results on efficacy imatinib treatment however, a recent Phase II trial patients with recurrent did demonstrate significant antitumor activity. To enhance activity imatinib, investigated use combination therapy nelfinavir...
Abstract Recent years have seen the emergence of conditionally activated diagnostics and therapeutics that leverage protease-cleavable peptide linkers to enhance their specificity for cancer. However, due a lack methods measure localize protease activity directly within tissue microenvironment, design protease-activated agents has been necessarily empirical, yielding suboptimal results when translated patients. To address need spatially resolved profiling in cancer, we developed new class...
ABSTRACT Recent years have seen the emergence of conditionally activated diagnostics and therapeutics that leverage protease-cleavable peptide linkers to enhance their specificity for cancer. However, due a lack methods measure localize protease activity directly within tissue microenvironment, design protease-activated agents has been necessarily empirical, yielding suboptimal results when translated patients. To address need spatially resolve d profiling in cancer, we developed new class...
A retrospective (case control) design was used to compare adolescents in treatment for alcohol and drug problems their families with not determine: (1) the extent which adolescents' drug-using behavior associated greater physical mental health services utilized by adolescent his/ her family members over a period of 3 years; (2) costs incurred maintenance organization social-psychological consequences individuals families. On average, those an and/or use more services, resulting prepaid plan...
Abstract Fructose‐1,6‐bisphosphate (FBP) is a high‐energy glycolytic intermediate that decreases the effects of ischemia; it has been used successfully in organ perfusion and preservation. How cells utilize external FBP to increase energy production mechanism by which molecule crosses membrane bilayer are unclear. This study examined on permeability, fluidity, phospholipid packing, potential determine how bilayer. Large unilamellar vesicles composed egg phosphatidylcholine (Egg PC) were made...
Abstract Diverse processes in cancer are mediated by enzymes, which most proximally exert their function through activity. Methods to quantify enzyme activity, rather than just expression, therefore critical our ability understand the pathological roles of enzymes and harness this class biomolecules as diagnostic therapeutic targets. Here we present an integrated set methods for measuring specific activities across organism, tissue, cellular levels, unify into a methodological hierarchy...
<div>Abstract<p>Recent years have seen the emergence of conditionally activated diagnostics and therapeutics that leverage protease-cleavable peptide linkers to enhance their specificity for cancer. However, due a lack methods measure localize protease activity directly within tissue microenvironment, design protease-activated agents has been necessarily empirical, yielding suboptimal results when translated patients. To address need spatially resolved profiling in cancer, we...
<p>Complete Supplementary Information for the manuscript, including Supplemental Figures 1-16 and tables 1-4.</p>
<p>Complete Supplementary Information for the manuscript, including Supplemental Figures 1-16 and tables 1-4.</p>
<div>Abstract<p>Recent years have seen the emergence of conditionally activated diagnostics and therapeutics that leverage protease-cleavable peptide linkers to enhance their specificity for cancer. However, due a lack methods measure localize protease activity directly within tissue microenvironment, design protease-activated agents has been necessarily empirical, yielding suboptimal results when translated patients. To address need spatially resolved profiling in cancer, we...
Background The TAR DNA binding protein, TDP‐43, has been recently identified to play a pathogenic role in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It shown that TDP43 mice expressing hTDP‐43DNLS develop set of phenotypes reminiscent ALS within few weeks. Magnetic resonance imaging (MRI) magnetic spectroscopy (MRS) offer quantitative multi‐modal assessment options can be exploited investigate neurodegeneration non‐invasively animal models ALS. Objectives To...