A5061089601- Heat shock proteins research
- Protein Structure and Dynamics
- Enzyme Structure and Function
- CAR-T cell therapy research
- Bacterial Genetics and Biotechnology
- Bacillus and Francisella bacterial research
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Lipid Membrane Structure and Behavior
- Cardiac Fibrosis and Remodeling
- Connexins and lens biology
- Cancer Immunotherapy and Biomarkers
- Genetic Neurodegenerative Diseases
- interferon and immune responses
- Immunotherapy and Immune Responses
- Hereditary Neurological Disorders
- HIV/AIDS drug development and treatment
- CRISPR and Genetic Engineering
- Toxin Mechanisms and Immunotoxins
- Advanced Biosensing Techniques and Applications
- Sphingolipid Metabolism and Signaling
- Endoplasmic Reticulum Stress and Disease
- Extracellular vesicles in disease
- Protist diversity and phylogeny
- Biochemical and Molecular Research
DecImmune Therapeutics (United States)
2024
École Polytechnique Fédérale de Lausanne
2015-2022
Massachusetts Institute of Technology
2012-2019
IIT@MIT
2015
Harvey Mudd College
2009
SARS-CoV-2 virions are surrounded by a lipid bilayer that contains membrane proteins such as spike, responsible for target-cell binding and virus fusion. We found during infection, spike becomes modified, through the sequential action of S-acyltransferases ZDHHC20 9. Particularly striking is rapid acylation on 10 cytosolic cysteines within ER Golgi. Using combination computational, lipidomics, biochemical approaches, we show this massive lipidation controls biogenesis degradation, drives...
Chaperonins are a family of chaperones that encapsulate their substrates and assist folding in an ATP-dependent manner. The ubiquitous eukaryotic chaperonin, TCP-1 ring complex (TRiC), is hetero-oligomeric composed two rings, each formed from eight different CCT (chaperonin containing TCP-1) subunits. Each subunit may have distinct substrate recognition ATP hydrolysis properties. We expressed human individually Escherichia coli to investigate whether they form chaperonin-like double...
To promote infections, pathogens exploit host cell machineries such as structural elements of the plasma membrane. Studying these interactions and identifying molecular players are ideal for gaining insights into fundamental biology cell. Here, we used anthrax toxin to screen a library 1,500 regulatory, cell-surface, membrane trafficking genes their involvement in intoxication process. We found that endoplasmic reticulum (ER)-Golgi-localized proteins TMED2 TMED10 required oligomerization at...
Huntington disease, a neurodegenerative disorder characterized by functional deficits and loss of striatal neurons, is linked to an expanded unstable CAG trinucleotide repeat in the huntingtin gene (HTT). This DNA sequence translates polyglutamine protein product, leading mutant (mHTT) aggregation. The aggregation mHTT inhibited vitro vivo TCP-1 ring complex (TRiC) chaperonin. Recently, novel comprised single type TRiC subunit has been reported inhibit Specifically, purified CCT5...
Abstract EVOLVE104 is the first CD3 T cell engager (TCE) being developed for solid tumors which utilizes integrated CD2 co-stimulation. a trispecific molecule targets ULBP2/5/6 on tumor and uses affinity-tuned engagement together with CD2-selective fusion protein to deliver coordinated costimulatory signal integration optimize its effector function. are closely related proteins of UL16 binding family recognized by NKG2D receptor induced cells while maintaining restricted expression normal...
The human chaperonin TRiC consists of eight non-identical subunits, and its protein-folding activity is critical for cellular health. Misfolded proteins are associated with many diseases, such as amyloid cancer, neuropathies, making a potential therapeutic target. A detailed structural understanding ATP-dependent folding mechanism substrate recognition therefore great importance. Of particular health-related interest the mutation Histidine 147 to Arginine (H147R) in subunit 5 (CCT5), which...
The protein acyl transferase ZDHHC5 was recently proposed to regulate trafficking in the endocytic pathway. Therefore, we explored function of this enzyme controlling action bacterial toxins. We found that activity is required for two very different toxins: anthrax lethal toxin and pore-forming aerolysin. Both these toxins have precursor forms, protoxins, which can use proprotein convertases Furin PC7 activation. show indeed affects processing protoxins their active forms. both be...
Archaeal and eukaryotic cytosols contain group II chaperonins, which have a double-barrel structure fold proteins inside cavity in an ATP-dependent manner. The most complex of the TCP-1 ring (TRiC), has eight different subunits, chaperone containing (CCT1-8), that are arranged so there is one each subunit per ring. Aspects function bovine yeast TRiC been characterized, but studies human limited. We isolated purified endogenous from HeLa suspension cells. This contained all CCT subunits...
<ns4:p>The anthrax toxin receptors—capillary morphogenesis gene 2 (CMG2) and tumor endothelial marker 8 (TEM8)—were identified almost 20 years ago, although few studies have moved beyond their roles as receptors for the toxins to address physiological functions. In last years, insight into endogenous has come from two rare diseases: hyaline fibromatosis syndrome, caused by mutations in CMG2, growth retardation, alopecia, pseudo-anodontia, optic atrophy (GAPO) loss-of-function TEM8. Although...
The eukaryotic cytosolic chaperonin, t-complex polypeptide 1 (TCP-1) ring complex or TRiC, is responsible for folding a tenth of the proteins in cell. TRiC double-ringed barrel with each composed eight different CCT (chaperonin containing TCP-1) subunits. In order subunits to assemble together into mature which believed contain one and only these per ring, they must be translated from chromosomes, correctly folded assembled. When expressed alone Escherichia coli, CCT4 CCT5, interestingly,...
SUMMARY SARS-CoV-2 virions are surrounded by a lipid bilayer which contains membrane proteins such as Spike, responsible for target-cell binding and virus fusion, the envelope protein E accessory Orf3a. Here, we show that during infection, all three become modified, through action of S-acyltransferase ZDHHC20. Particularly striking is rapid acylation Spike on 10 cytosolic cysteines within ER Golgi. Using combination computational, lipidomics biochemical approaches, this massive lipidation...
Abstract Bispecific antibodies which bind a tumor antigen and the CD3 heterodimer of T cell receptor to form synthetic immunological synapse represent class engagers that has been clinically validated with approvals blinatumomab (Blinctyo®) mosunetuzumab (Lunsumio®), targeting CD19 CD20 respectively, for treatment B acute lymphoblastic leukemia follicular lymphoma. Despite being potent therapeutics, not all patients respond therapy. Recent studies into state blinatumomab-treated cells...
<h3>Background</h3> There have been significant advances in breast cancer treatments, including endocrine, Her2-targeted, chemotherapies, and immune checkpoint inhibitors. However, treatment-resistant, metastatic, recurrent disease often lead to poor patient outcomes, highlighting the need for more effective durable therapies. B7-H4 is an attractive target due its frequent robust expression cancers relatively low normal tissues. Our gene analysis of tumors indicated significantly higher...
Abstract The features in partially folded intermediates that allow the group II chaperonins to distinguish from native states remain unclear. archaeal chaperonin Methanococcus Mauripaludis (Mm‐Cpn) assists vitro refolding of well‐characterized β‐sheet lens protein human γD‐crystallin (HγD‐Crys). domain interface and buried cores this Greek key conformation include side chains, which might be exposed intermediates. We sought assess whether particular state, but absent surface, serve as...
Abstract Despite the recent approvals of CD20-targeted CD3 bispecific molecules in follicular lymphoma (Lunsumio™, mosunetuzumab) and diffuse large B cell (Columvi™, glofitamab; Epkinly™, epcoritamab), significant opportunities to improve patient outcomes these indications remain. Targeted induction T costimulatory receptors (signal 2) as a complement activation mediated by receptor signal 1 is an attractive strategy sustain optimize redirected effector response tumors. Drug combinations...
<h3>Background</h3> EVOLVE104 is the first CD3 T cell engager (TcE) being developed for solid tumors which utilizes integrated CD2 costimulation to enhance durable effector function. a trispecific molecule targets ULBP2/5/6 on tumor and uses an affinity-tuned binder together with CD2-selective fusion protein deliver coordinated costimulatory signal integration cell. are closely related proteins of UL16 binding family recognized by NKG2D receptor induced cells while maintaining restricted...
Abstract T cell exhaustion is a hallmark of tumor-infiltrating cells and major therapeutic challenge for immunotherapy which not sufficiently understood. To identify promoting genes may be targeted by new therapies, we combined highly efficient CRISPR/Cas9 gene knockouts in primary human with functional assessment effector function under exhaustion-inducing chronic activation conditions. We conducted an initial screen focused on previously identified reported as enhancers anti-tumor response...
<h3>Background</h3> Recurrent and treatment-refractory solid tumors are especially lethal, leading to the spread of distant sites forming metastases in vital tissues, primary cause death tumor patients. Distinct lineages implicated as source these owing ability persist regardless treatment potential actively suppress anti-tumor immunity. However, tractable targets preferentially expressed have not been determined. The identification such tumor-associated antigens for T cell-redirecting...
SARS-CoV-2 virions are surrounded by a lipid bilayer which contains membrane proteins such as Spike, responsible for target-cell binding and virus fusion, the envelope protein E accessory Orf3a. Here, we show that during infection, all three become modified, through action of S- acyltransferase ZDHHC20. Particularly striking is rapid acylation Spike on 10 cytosolic cysteines within ER Golgi. Using combination computational, lipidomics biochemical approaches, this massive lipidation controls...