A5091462299- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- HER2/EGFR in Cancer Research
- Advanced Fluorescence Microscopy Techniques
- Epigenetics and DNA Methylation
- Lymphoma Diagnosis and Treatment
- Enzyme Structure and Function
- Electrochemical Analysis and Applications
- Prostate Cancer Treatment and Research
- Nanoplatforms for cancer theranostics
- Bacterial Genetics and Biotechnology
- Protein purification and stability
- Nuclear Receptors and Signaling
- Click Chemistry and Applications
- Force Microscopy Techniques and Applications
- Photodynamic Therapy Research Studies
- Ferroptosis and cancer prognosis
- Bacteriophages and microbial interactions
- Estrogen and related hormone effects
- Mass Spectrometry Techniques and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Endometriosis Research and Treatment
- Immune cells in cancer
- Urological Disorders and Treatments
Michigan State University
2025
Sutro Biopharma (United States)
2015-2024
National Cancer Institute
2004-2019
Center for Cancer Research
2004-2018
National Institutes of Health
2006-2017
Hanson & Associates (United Kingdom)
2015
University of California, Berkeley
2008-2013
Princeton University
2009-2011
Frederick National Laboratory for Cancer Research
2008
Division of Cancer Epidemiology and Genetics
2008
Many enzymes mold their structures to enclose substrates in active sites such that conformational remodeling may be required during each catalytic cycle. In adenylate kinase (AK), this involves a large-amplitude rearrangement of the enzyme's lid domain. Using our method high-resolution single-molecule FRET, we directly followed AK's domain movements on its time scale. To quantitatively measure entire distribution, have applied maximum entropy-based methods remove photon-counting noise from...
Gene expression can be silenced through the methylation of specific sites in promoter region. This mechanism gene silencing has an important role carcinogenesis prostate and other cancers. Although tumor-associated stromal cells also exhibit changes expression, not been described these cells.Tumor epithelia, stroma normal adjacent to tumor tissues were isolated from whole-mount prostatectomy specimens (two per patient) patients (n = 5) with localized cancer epithelia benign hyperplasia men...
Abstract Brain metastases are devastating complications of cancer. The blood–brain barrier (BBB), which protects the normal brain, morphs into an inadequately characterized blood–tumor (BTB) when brain form, and is surrounded by a neuroinflammatory response. These structures contribute to poor therapeutic efficacy limiting drug uptake. Here, we report that experimental breast cancer low- high permeability dextran dye exhibit distinct microenvironmental gene expression patterns. Astrocytic...
Cell‐free protein synthesis (CFPS) systems allow for robust expression with easy manipulation of conditions to improve yield and folding. Recent technological developments have significantly increased the productivity reduced operating costs CFPS systems, such that they can compete conventional in vivo production platforms, while also offering new routes discovery biotherapeutics. As cell‐free evolved, increases commonly been obtained by addition components previously designed reaction...
STRO-002 is a novel homogeneous folate receptor alpha (FolRα) targeting antibody-drug conjugate (ADC) currently being investigated in the clinic as treatment for ovarian and endometrial cancers. Here, we describe discovery, optimization, antitumor properties of STRO-002. was generated by conjugation cleavable 3-aminophenyl hemiasterlin linker-warhead (SC239) to nonnatural amino acid para-azidomethyl-L-phenylalanine incorporated at specific positions within high affinity anti-FolRα antibody...
AbstractUp to 30% of men with clinically localized disease who receive radical prostatectomy develop a biochemical recurrence. Gene methylation in tumor tissue may distinguish aggressive cancer. This study evaluated GSTP1, RARβ2, CD44 and PTGS2 recurrence among 60 patients underwent using logistic regression Kaplan Meier time event analysis. Methylation GSTP1 RARβ2 was not associated recurrence, however, were significant predictors. In multivariate models adjusting for Gleason grade, profile...
Abstract BACKGROUND Gene methylation may contribute to prostate carcinogenesis through the silencing of gene transcription. We report on status several genes shown be silenced at different stages progression using whole mount specimens and laser capture microdissection. This is first study evaluate patterns across multiple pre‐cancerous invasive cancer foci from same gland. METHODS Real‐time PCR was used five ( GSTP1 , RASSF1A RARβ2 CD44 EDNRB ) normal epithelium, high‐grade prostatic...
Protein biosynthesis requires numerous conformational rearrangements within the ribosome. The structural core of ribosome is composed RNA and therefore dependent on counterions such as magnesium ions for function. Many steps translation can be compromised or inhibited if concentration Mg(2+) too low high. Conditions previously used to probe conformation mammalian in vitro high concentrations that we find completely inhibit vitro. We have probed small ribosomal subunit support compared it...
Background/Objectives: Iron deficiency anemia is common in the pediatric population. Red blood cell transfusions, a acute treatment, pose well-recognized risks including lung injury, circulatory overload, and immune dysfunction. Intravenous iron, specifically sodium ferric gluconate complex (SFGC), potential alternative, however investigation on its use hospitalized children lacking. This study aims to describe physiologic response via change hematologic values cumulative dose of SFGC,...
The crucial step in drug discovery is the identification of a lead compound from vast chemical library by any number screening techniques. NMR-based has advantage directly detecting binding to target. spectra resulting these screens can also be very complex and difficult analyze, making this an inefficient process. We present here method, RAMPED-UP NMR, (Rapid Analysis Multiplexing Experimentally Discriminated Uniquely Labeled Proteins using NMR) which generates simple are easy interpret...
The Mycobacterium tuberculosis protein tyrosine phosphatase PtpB shows resistance to the oxidative conditions that prevail within an infected host macrophage, but mechanism of this molecular adaptation is unknown. Crystal structures revealed previously a closed, two-helix lid covers active site. By measuring single-molecule Förster-type resonance energy transfer probe dynamics two helices constitute lid, we obtained direct evidence for large, spontaneous opening transitions with closed form...
The XpressCF+® cell-free protein synthesis system is a robust platform for the production of non-natural amino acids containing antibodies, which enable site-specific conjugation homogeneous antibody drug conjugates (ADCs) via click chemistry. Here, we present and scalable means achieving 50-100% increase in IgG titers by combining high productivity cell-based with unique ability reactions to produce correctly folded assembled IgGs multiple at defined positions. This hybrid technology...
The process of arteriogenesis after occlusion a major artery is poorly understood. We have used high-resolution microcomputed tomography (mu-CT) imaging to define the arteriogenic response in mouse model hindlimb ischemia and examine effect placental growth factor-1 (PlGF-1) on this process.After common femoral ligation, mu-CT demonstrated formation collateral vessels originating near ligation site upper limb connecting ischemic calf muscle region. Three-dimensional quantitative image...
We report evidence that adenylate kinase (AK) from Escherichia coli can be activated by the direct binding of a magnesium ion to enzyme, in addition ATP-complexed Mg(2+). By systematically varying concentrations AMP, ATP, and kinetic experiments, we found apparent substrate inhibition AK, formerly attributed was suppressed at low enhanced high concentrations. This previously unreported dependence accounted for modified random bi-bi model which Mg(2+) bind AK directly prior AMP binding. A new...
The statistical properties of the cross correlation between two time series has been studied. An analytical expression for function's variance derived. On basis these results, a statistically robust method proposed to detect existence and determine direction series. characterized by computer simulations. Applications single-molecule fluorescence spectroscopy are discussed. results may also find immediate applications in (FCS) its variants.
Recent advances in cell-free protein synthesis have enabled the folding and assembly of full-length antibodies at high titers with extracts from prokaryotic cells. Coupled facile engineering Escherichia coli translation machinery, E. based vitro reactions emerged as a leading source IgG molecules nonnatural amino acids incorporated specific locations for producing homogeneous antibody-drug conjugates (ADCs). While this has been demonstrated extract produced batch fermentation mode,...
The statistical properties of the autocorrelation function from a time series composed independently and identically distributed stochastic variables has been studied. Analytical expressions for function’s variance have derived. It found that two common ways calculating autocorrelation, moving-average Fourier transform, exhibit different uncertainty characteristics. For periodic series, transform method is preferred because it gives smaller uncertainties are uniform through all lags. Based...
As analytical technologies in proteomics and metabolomics continue to mature, there is an increasing need apply these clinically relevant biologic samples. In this study, a liquid chromatography−tandem mass spectrometry method that utilizes selected reaction monitoring was used measure the absolute quantity of estrogens estrogen metabolites testosterone 8-μm tissue sections obtained from fresh frozen lymph node tumor infiltrated by metastatic breast carcinoma. Total (conjugated plus...
Antibody–drug conjugates (ADCs) are antigen-targeted therapeutics that employ antibodies to deliver potent, cytotoxic effectors cells with potentially high specificity. While promising clinical results have been achieved, significant pitfalls remain including internalization of ADCs in nontargeted expressing target antigen, which can limit therapeutic windows. Novel ADC linkers cleaved selectively cancer but not normal could minimize collateral damage caused by uptake tissues. Here, we...