A5076461307- CAR-T cell therapy research
- Virus-based gene therapy research
- Parkinson's Disease Mechanisms and Treatments
- Nuclear Structure and Function
- DNA Repair Mechanisms
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Cytokine Signaling Pathways and Interactions
- Autophagy in Disease and Therapy
- Lysosomal Storage Disorders Research
- Immune Cell Function and Interaction
- Viral Infectious Diseases and Gene Expression in Insects
- Immunotherapy and Immune Responses
- Plant Gene Expression Analysis
- Bacterial Genetics and Biotechnology
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Immunotherapy and Biomarkers
- Microfluidic and Bio-sensing Technologies
- Microtubule and mitosis dynamics
- interferon and immune responses
- Cellular transport and secretion
- Microfluidic and Capillary Electrophoresis Applications
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
Torque (United States)
2019-2020
Brigham and Women's Hospital
2011-2017
Harvard University
2013-2017
Center for Neuro-Oncology
2014
SUNY Upstate Medical University
2009-2012
Skidmore College
2005
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial and idiopathic Parkinson's disease. However, mechanisms for activating its physiological function not known, hindering identification biological role endogenous LRRK2. The recent discovery that LRRK2 is highly expressed cells innate immune system genetic association a risk factor autoimmune disorders implies an important pathology outside central nervous system. Thus, examination could provide insight...
Immune-activating cytokines such as interleukin-12 (IL-12) hold strong potential for cancer immunotherapy but have been limited by high systemic toxicities. We describe here an approach to safely harness cytokine biology adoptive cell therapy through uniform and dose-controlled tethering onto the surface of adoptively transferred cells. Tumor-specific T cells tethered with IL-12 showed superior antitumor efficacy across multiple models compared conventional coadministration. Mechanistically,...
Abstract Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, affecting 1–3% of population over 65. Mutations in ubiquitin E3 ligase parkin are common cause autosomal recessive PD. The protein possesses potent cell-protective properties and has been mechanistically linked to both regulation apoptosis turnover damaged mitochondria. Here, we explored these two functions relative scale processes various cell types. While biochemical analyses subcellular...
The Vaccinia virus H1 gene product, VH1, is a dual specificity phosphatase that down-regulates the cellular antiviral response by dephosphorylating STAT1. crystal structure of determined at 1.32 Å resolution, reveals novel dimeric quaternary structure, which exposes two active sites spaced ∼39 away from each other. VH1 forms stable dimer via an extensive domain swap N-terminal helix (residues 1-20). In vitro, can dephosphorylate activated STAT1, in reaction competed nuclear transport adapter...
The rate of the alkaline phosphatase-catalyzed hydrolysis 4-methylumbelliferone phosphate was measured in acoustically levitated droplets aqueous tris (50 mM) at pH 8.5 22 ± 2 °C and supercooled solution −6 °C. At °C, product formation excellent agreement with observed bulk a cuvette, indicating that acoustic levitation process does not alter enzyme activity. reaction decreased 6-fold levitator apparatus is described detail.
Abstract Interleukin-12 (IL-12) is a potent pro-inflammatory cytokine that augments anti-tumor immune responses by promoting CD4 T cell Th1 differentiation, increasing CD8 and NK cytotoxicity, inducing MHC expression on antigen presenting cells, reprogramming myeloid-derived suppressor cells. However, the clinical utility of IL-12 has been limited systemic toxicities. DeepTM fusion protein between Fab antibody against CD45, an abundant surface receptor This enables tethering onto cells prior...
Missense mutation of the PARK8 gene, which encodes protein Leucine‐Rich Repeat Kinase 2 (LRRK2), is most common genetic cause Parkinson's Disease (PD), yet physiological role this largely unknown. LRRK2 dimerization has been linked to its activity and localization in cell, as dimers have higher kinase are preferentially membrane‐associated. In study we utilized a Split‐Luciferase Protein‐ Fragment‐Assisted Complementation assay (PCA) assess LRRK2. PCA numerous advantages over other...
Homologous recombination (HR), an error free DNA repair mechanism, is poorly understood in mitochondria. This evolutionarily conserved from bacteriophage to humans, has evolved primarily as a strategy for the of double strand breaks. The recombinational breaks may proceed by two distinct pathways. conventional pathway requires RecA/Rad51‐type recombinase that catalyzes invasion. alternative involves Rad52‐type proteins, which promote single annealing. proteins inherently form rings and...
Introduction Interleukin-12 (IL-12) is a potent cytokine that augments anti-tumor immune responses by promoting CD4 T cell Th1 differentiation, increasing CD8 and NK cytotoxicity, inducing MHC expression on antigen presenting cells, reprogramming myeloid-derived suppressor cells. However, the clinical utility of IL-12 administered systemically or produced genetically engineered tumor-specific cells has been limited toxicities. DeepTM fusion protein between Fab antibody against CD45, an...
Abstract Introduction Interleukin-12 (IL-12) is a potent cytokine that augments anti-tumor immune responses by promoting CD4 T cell Th1 differentiation, increasing CD8 and NK cytotoxicity, inducing MHC expression on antigen presenting cells, reprogramming myeloid-derived suppressor cells. However, the clinical utility of IL-12 administered systemically or produced genetically engineered tumor-specific cells has been limited toxicities. DeepTM fusion protein between Fab antibody against CD45,...
Abstract Background: Interleukin-15 (IL-15) and interleukin-12 (IL-12) play complementary roles as immunomodulators. IL-15 induces T-cell memory supports survival, activation, proliferation of CD8 T NK cells. IL-12 promotes cytotoxicity innate immune responses in the tumor microenvironment (TME). Both cytokines have been explored cancer immunotherapies, but severe side effects limited clinical success. Torque has developed Deep-PrimedTM therapy technology to direct stimulatory activity these...
<h3>Background</h3> Acquired resistance is a major limiting factor for durable T cell therapies in solid tumors. Antigen escape pathways such as insufficient antigen coverage or loss of target remain mechanisms that need to be addressed order expand the field therapies.Interleukin-12 (IL-12) potent stimulator innate and adaptive immune cells holds strong potential cancer immunotherapy, but its clinical utility has been limited by high systemic toxicities. We have previously shown tethering...