A5069092297- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Prostate Cancer Treatment and Research
- Glycosylation and Glycoproteins Research
- Single-cell and spatial transcriptomics
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
- Carbohydrate Chemistry and Synthesis
- RNA Research and Splicing
- Axon Guidance and Neuronal Signaling
- Monoclonal and Polyclonal Antibodies Research
- Molecular Biology Techniques and Applications
- Radiomics and Machine Learning in Medical Imaging
- 3D Printing in Biomedical Research
- Microfluidic and Bio-sensing Technologies
- Cancer-related molecular mechanisms research
- Hearing, Cochlea, Tinnitus, Genetics
- Genetic factors in colorectal cancer
- Hippo pathway signaling and YAP/TAZ
- Chromatography in Natural Products
- Lung Cancer Diagnosis and Treatment
- Cancer Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- Cancer survivorship and care
- Protein Kinase Regulation and GTPase Signaling
University of Southern California
2015-2024
USC Norris Comprehensive Cancer Center
2024
Convergent Science (United States)
2017-2024
Scripps Research Institute
2008-2019
Institute for Molecular Medicine
2017
University of California, Los Angeles
2017
La Jolla Alcohol Research
2012
Stanford University
1996-2002
University of Oxford
2000
Institute of Biophysics
1996
Hematologic spread of carcinoma results in incurable metastasis; yet, the basic characteristics and travel mechanisms cancer cells bloodstream are unknown. We have established a fluid phase biopsy approach that identifies circulating tumor (CTCs) without using surface protein-based enrichment presents them sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. This 'HD-CTC' assay finds >5 HD-CTCs mL−1 blood 80% patients with metastatic prostate (n =...
The asialoglycoprotein receptors and many other C-type (Ca2⁺-dependent) animal lectins specifically recognize galactose- or N-acetylgalactosamine-terminated oligosaccharides. Analogous binding specificity can be engineered into the homologous rat mannose-binding protein A by changing three amino acids inserting a glycine-rich loop (Iobst, S. T., Drickamer, K.(1994) J. Biol. Chem. 269, 15512-15519). Crystal structures of this mutant complexed with β-methyl galactoside N-acetylgalactosamine...
Circulating tumor cells (CTCs) have been implicated as a population of that may seed metastasis and venous thromboembolism (VTE), two major causes mortality in cancer patients. Thus far, existing CTC detection technologies unable to reproducibly detect aggregates order address what contribution make or VTE. We report here an enrichment-free immunofluorescence method can enumerate homotypic patient samples. identified 43% 86 The fraction aggregation was investigated blood draws from 24...
Timely characterization of a cancer's evolution is required to predict treatment efficacy and detect resistance early. High content analysis single Circulating Tumor Cells (CTCs) enables sequential genotypic, morphometric protein expression alterations in real time over the course cancer treatment. This concept was investigated patient with castrate-resistant prostate progressing through both chemotherapy targeted therapy. In this case study, we integrate across four timepoints 41...
Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, recent data suggest a similar role late stage non-small lung cancer (NSCLC). However, due to sensitivity constraints current enrichment-based CTC detection technologies, there few published about prevalence rates morphologic heterogeneity early-stage NSCLC, or the correlation of CTCs with disease progression their usability for clinical staging. We investigated...
Sampling circulating tumor cells (CTCs) from peripheral blood is ideally accomplished using assays that detect high numbers of and preserve them for downstream characterization. We sought to evaluate a method enrichment free fluorescent labeling CTCs followed by automated digital microscopy in patients with non-small cell lung cancer. Twenty-eight cancer hematogenously seeded metastasis were analyzed multiple draws. detected 68% samples found propensity increased CTC detection as the disease...
Deafness is the most common form of sensory impairment in humans and frequently caused by single gene mutations. Interestingly, different mutations a can cause syndromic nonsyndromic forms deafness, as well progressive age-related hearing loss. We provide here an explanation for phenotypic variability associated with cadherin 23 (CDH23). CDH23 null alleles deaf-blindness (Usher syndrome type 1D; USH1D), whereas missense deafness (DFNB12). In forward genetic screen, we have identified salsa...
Clinical studies have demonstrated that circulating tumor cells (CTCs) are present in the blood of cancer patients with known metastatic disease across major types epithelial malignancies. Recent shown concentration CTCs is prognostic overall survival breast, prostate, colorectal, and non-small cell lung cancer. This study characterizes identified using high-definition (HD)-CTC assay an ovarian patient stage IIIC disease. We characterized physical properties 31 HD-CTCs 50 normal leukocytes...
Molecular analysis of circulating and disseminated tumor cells (CTCs/DTCs) has great potential as a means for continuous evaluation prognosis treatment efficacy in near-real time through minimally invasive liquid biopsies. To realize this potential, however, methods molecular these rare must be developed validated. Here, we describe the integration imaging mass cytometry (IMC) using metal-labeled antibodies implemented on Fluidigm Hyperion Imaging System into workflow previously established...
Abstract Purpose: Aggressive variant prostate cancer (AVPC) represents a clinical subset distinguished by therapy resistance and poor prognosis, linked to combined losses of the tumor suppressor genes (TSG) PTEN, RB1, TP53. Circulating cells (CTC) provide minimally invasive opportunity for identification molecular characterization AVPC. We aimed evaluate incidence significance compound (2+)TSG genomic instability in CTC, expand set biomarkers relevant Experimental Design: Genomic analysis...
The mannose receptor of macrophages and liver endothelium mediates clearance pathogenic organisms potentially harmful glycoconjugates. extracellular portion the includes eight C-type carbohydrate recognition domains (CRDs), which one, CRD-4, shows detectable binding to monosaccharide ligands. We have determined crystal structure CRD-4. Although basic lectin fold is preserved, a loop extends away from core domain form domain-swapped dimer in crystal. Of two Ca<sup>2+</sup> sites, only...
Circulating tumor cells (CTC) have been implicated in the hematogenous spread of cancer. To investigate fluid phase cancer from a physical sciences perspective, multi-institutional Physical Sciences-Oncology Center (PS-OC) Network performed multidisciplinary biophysical studies single CTC and aggregates patient with breast CTCs, ranging to comprised 2-5 cells, were isolated using high-definition assay biophysically profiled quantitative microscopy. Single CTCs then modeled an vitro system...
Abstract Metastatic castration-resistant prostate cancer (mCRPC) includes a subset of patients with particularly unfavorable prognosis characterized by combined defects in at least two three tumor suppressor genes: PTEN, RB1, and TP53 as aggressive variant molecular signature (AVPC-MS). We aimed to identify circulating cells (CTC) signatures that could inform treatment decisions mCRPC cabazitaxel–carboplatin combination therapy versus cabazitaxel alone. Liquid biopsy samples were collected...
Abstract Little is known about the complexity and plasticity of circulating tumor cell (CTC) biology in different compartments fluid microenvironment during metastasis. Here we integrated phenomics, genomics, targeted proteomics to characterize CTC phenotypic genotypic heterogeneity paired peripheral blood (PB) bone marrow aspirate (BMA) from a metastatic prostate cancer patient following rapid disease progression, using High-Definition Single Cell Assay 3.0 (HDSCA3.0). Uniquely, identified...
The mammalian hepatic asialoglycoprotein receptor, a member of the C-type animal lectin family, displays preferential binding to <i>N</i>-acetylgalactosamine compared with galactose. structural basis for selective to<i>N</i>-acetylgalactosamine has been investigated. Regions carbohydrate-recognition domain receptor believed be important in have inserted into homologous mannose-binding protein mutant that was previously altered bind Introduction single histidine residue corresponding 256...
Mannose-binding proteins (MBPs) are C-type animal lectins that recognize high mannose oligosaccharides on pathogenic cell surfaces. MBPs bind to their carbohydrate ligands by forming a series of Ca2+ coordination and hydrogen bonds with two hydroxyl groups equivalent the 3- 4-OH mannose. In this work, determinants orientation sugars bound rat serum liver (MBP-A MBP-C) have been systematically investigated. The crystal structures MBP-A soaked monosaccharides disaccharides also structure...
The cadherin superfamily encodes more than 100 receptors with diverse functions in tissue development and homeostasis. Classical cadherins mediate adhesion by binding interactions that depend on their N-terminal extracellular (EC) domains, which swap beta-strands. Sequence alignments suggest the strand-swap mode is not commonly used functionally divergent cadherins. Here, we have determined structure of EC1-EC2 domains 23 (CDH23), binds to protocadherin 15 (PCDH15) form tip links...
Context.— As circulating tumor cell (CTC) assays gain clinical relevance, it is essential to address preanalytic variability and develop standard operating procedures for sample handling in order successfully implement genomically informed, precision health care. Objective.— To evaluate the effects of blood collection tube (BCT) type time-to-assay (TTA) on enumeration high-content characterization CTCs by using high-definition single-cell assay (HD-SCA). Design.— Blood samples patients with...
Purpose. Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization CMCs has been limited due to the lack robust methodology capable identifying them format suitable for downstream characterization. Here, we have developed detect intact that enables phenotypic, morphometric and analysis at single cell level. Experimental design. Blood samples from 40 metastatic patients 10 normal blood...