A5005109179- Peptidase Inhibition and Analysis
- Synthesis and Biological Evaluation
- CAR-T cell therapy research
- Genetic Neurodegenerative Diseases
- Signaling Pathways in Disease
- Mitochondrial Function and Pathology
- Parkinson's Disease Mechanisms and Treatments
- Lymphoma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Radiopharmaceutical Chemistry and Applications
- Knee injuries and reconstruction techniques
- Research in Cotton Cultivation
- Pesticide Exposure and Toxicity
- Plant nutrient uptake and metabolism
- biodegradable polymer synthesis and properties
- Cancer therapeutics and mechanisms
- interferon and immune responses
- Cellular transport and secretion
- Advanced biosensing and bioanalysis techniques
- Prion Diseases and Protein Misfolding
- Cardiomyopathy and Myosin Studies
- Immunodeficiency and Autoimmune Disorders
- DNA Repair Mechanisms
- Lipid metabolism and biosynthesis
- Protein Degradation and Inhibitors
University of Pennsylvania
2006-2025
California University of Pennsylvania
2024
Children's Hospital of Philadelphia
2015-2016
Howard Hughes Medical Institute
2006-2010
University of Missouri–Kansas City
2006
Whitehead Institute for Biomedical Research
2006
Shanghai Institutes for Biological Sciences
2002-2003
Chinese Academy of Sciences
2002-2003
Center for Excellence in Molecular Plant Sciences
2002-2003
Alpha-synuclein (alphaSyn) misfolding is associated with several devastating neurodegenerative disorders, including Parkinson's disease (PD). In yeast cells and in neurons alphaSyn accumulation cytotoxic, but little known about its normal function or pathobiology. The earliest defect following expression was a block endoplasmic reticulum (ER)-to-Golgi vesicular trafficking. genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, Rab guanosine...
Inherited mutations in PARK7, the gene encoding DJ-1, are associated with loss of protein function and early-onset parkinsonism. Like human DJ-1 (hDJ-1), Drosophila DJ-1b protects against oxidative insult is modified oxidation. We demonstrate that hDJ-1 rescues flies mutant for DJ-1b, a conserved cysteine residue fly (C104, analogous to C106 hDJ-1) critical biological antioxidant vivo. Targeted mutagenesis suggests modification at this inactivates protective activity stress. Further studies...
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that leads to loss of function and early death. About 5% cases are inherited, with the majority identified linkages in gene encoding copper, zinc-superoxide dismutase (SOD1). Strong evidence indicates SOD1 mutations confer dominant toxicity on protein. To provide new insight into mechanisms ALS, we have generated characterized model for familial ALS Drosophila transgenic expression human SOD1. Expression wild type or...
Despite the success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies, successful targeting solid tumors with CAR T cells has been limited by a lack durable responses and reports toxicities. Our understanding therapeutic efficacy in could be improved quantitative tools that allow characterization T-targeted antigens accurate monitoring response.
Monoclonal antibodies are highly specific for their targets making them effective cancer therapy. However, large molecular weight causes slow blood clearance, often requiring weeks to be removed from circulation. This limitation affects companion nuclear imaging and antibody-based diagnostics, necessitating delayed imaging. We report the expansion of a methodology improving positron emission tomography (PET) contrast lymphoma biomarker CD20 at early time points after radiolabeled antibody...
We have isolated a cDNA (GhWBC1) from cotton (Gossypium hirsutum) that encodes an ATP-binding cassette transporter of the WBC (white/brown complex) subfamily. Members this subfamily are half-sized transporters and reported to mediate lipid drug excretion in human (Homo sapiens). GhWBC1 is highly expressed developing fiber cells, but transcripts were also detectable other tissues except roots. The transcript level peaked rapidly expanding fibers 5 9 DPA then decreased. expression was weak...
Protein cleavage is a common feature in human neurodegenerative disease. Ataxin-3 protein with an expanded polyglutamine (polyQ) repeat causes spinocerebellar ataxia type-3 (SCA3), also called Machado–Joseph disease, and cleaved mammalian cells, transgenic mice SCA3 patient brain tissue. However, the pathological significance of has not been carefully examined. To gain insight into cleavage, we developed Drosophila SL2 cell-based model as well fly models. Our data indicate that conserved may...
Abstract Temporal control of protein levels in cells and living animals can be used to improve our understanding function. In addition, engineered proteins could therapeutic applications. PRoteolysis-TArgeting Chimeras (PROTACs) have emerged as a small-molecule-driven strategy achieve rapid, post-translational regulation abundance via recruitment an E3 ligase the target interest. Here, we develop several PROTAC molecules by covalently linking antibiotic trimethoprim (TMP) pomalidomide,...
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease among children, etiology of which involves a strong genetic component, but much underlying determinants still remain unknown. Our aim was to identify novel variants that predispose JIA. We performed genome-wide association study (GWAS) and replication in total 1166 JIA cases 9500 unrelated controls European ancestry. Correlation SNP genotype gene expression investigated. Then we conducted targeted resequencing...
Absence of the anterior (ACL) or posterior cruciate ligament (PCL) are rare congenital malformations that result in knee joint instability, with a prevalence 1.7 per 100,000 live births and can be associated other lower-limb abnormalities such as ACL agnesia absence menisci knee. While few cases ACL/PCL reported literature, number large familial case series related conditions suggest potential underlying monogenic etiology. We performed whole exome sequencing family two individuals affected...
Abstract Trinucleotide repeat instability underlies >20 human hereditary disorders. These diseases include many neurological and neurodegenerative situations, such as those caused by pathogenic polyglutamine (polyQ) domains encoded expanded CAG repeats. Although mechanisms of have been intensely studied, our knowledge remains limited in part due to the lack unbiased genome-wide screens multicellular eukaryotes. Drosophila melanogaster displays triplet with features that recapitulate...
The propensity of proteins to form β-sheet-rich amyloid fibrils is related a variety biological phenomena, including number human neurodegenerative diseases and prions. A subset amyloidogenic forms through glutamine/asparagine (Q/N)-rich domains, such as pathogenic polyglutamine (poly(Q)) involved in disease, well yeast In the former, an expanded poly(Q) tract abnormally fold confers toxicity on respective protein, leading neuronal dysfunction. latter, Q/N-rich prion domains mediate protein...
Abstract Monoclonal antibodies have had a remarkable impact on cancer therapy due to their high target specificity. However, large molecular weight results in slow blood clearance, which can take weeks clear from circulation. As companion nuclear imaging and diagnostic tools, these characteristics force delayed the use of isotopes with long half-lives such as 89 Zr. For optimal clinical application, it is desirable that radioimmunoconjugates remain for just enough time accumulate adequately...
Supplementary Data from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74
Supplementary Figure from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74
Supplementary Data from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74
Supplementary Data from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74
<div>AbstractPurpose:<p>Despite the success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies, successful targeting solid tumors with CAR T cells has been limited by a lack durable responses and reports toxicities. Our understanding therapeutic efficacy in could be improved quantitative tools that allow characterization T–targeted antigens accurate monitoring response.</p>Experimental Design:<p>We used radiolabeled FAP inhibitor (FAPI)...
Supplementary Data from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74
<div>AbstractPurpose:<p>Despite the success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies, successful targeting solid tumors with CAR T cells has been limited by a lack durable responses and reports toxicities. Our understanding therapeutic efficacy in could be improved quantitative tools that allow characterization T–targeted antigens accurate monitoring response.</p>Experimental Design:<p>We used radiolabeled FAP inhibitor (FAPI)...
Supplementary Data from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74