A5037642577- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Genomic variations and chromosomal abnormalities
- Cancer-related Molecular Pathways
- RNA and protein synthesis mechanisms
- Cancer Cells and Metastasis
- Microtubule and mitosis dynamics
- Lipid Membrane Structure and Behavior
- Advanced Breast Cancer Therapies
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Protein Structure and Dynamics
- Lung Cancer Research Studies
- Mathematical Biology Tumor Growth
- Genetic factors in colorectal cancer
- Radiomics and Machine Learning in Medical Imaging
- Advanced biosensing and bioanalysis techniques
- AI in cancer detection
- Genetics, Bioinformatics, and Biomedical Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Pancreatic and Hepatic Oncology Research
The University of Texas MD Anderson Cancer Center
2015-2022
The University of Texas Health Science Center at Houston
2017-2021
University of Houston
2016
Johnson University
2013
Metastasis is a complex biological process that has been difficult to delineate in human colorectal cancer (CRC) patients. A major obstacle understanding metastatic lineages the extensive intra-tumor heterogeneity at primary and tumor sites. To address this problem, we developed highly multiplexed single-cell DNA sequencing approach trace of two CRC patients with matched liver metastases. Single-cell copy number or mutational profiling was performed, addition bulk exome targeted...
In single cell DNA and RNA sequencing experiments, the number of cells to sequence must be decided before running an experiment, afterwards, it is necessary decide whether sufficient were sampled. These questions can addressed by calculating probability sampling at least a defined from each subpopulation (cell type or cancer clone).We developed interactive web application called SCOPIT (Single-Cell One-sided Probability Interactive Tool), which calculates required probabilities using...
Computational methods have been developed to reconstruct evolutionary lineages from tumors using single-cell genomic data. The resulting tumor trees important applications in cancer research and clinical oncology. Please see related Research articles: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0929-9 http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0936-x .
Outer membrane β-barrel proteins differ from α-helical inner in lipid environment, secondary structure, and the proposed processes of folding insertion. It is reasonable to expect that outer may contain primary sequence information specific for their insertion behavior. In previous work, a depth-dependent potential, E(z) , was derived proteins. We have generated an equivalent potential TM The similarities differences between these two potentials provide insight into unique aspects This can...
Triple-negative breast cancer (TNBC) is a heterogeneous group of estrogen, progesterone, and HER2-negative cancers with poor clinical outcomes. The imipridone ONC201 G-protein-coupled dopamine receptor D2 modulator an allosteric agonist the mitochondrial protease caseinolytic P(ClpP), which induces apoptosis. Here, we aimed to develop novel ONC201-based combination therapy targeting TNBC. We performed reverse-phase protein array analysis ONC201-treated/-untreated -sensitive/-resistant cell...
Abstract High-throughput methods for single cell copy number sequencing have enabled the profiling of thousands cells in parallel, yet there remains a significant bottleneck data analysis. Here we present CopyKit, comprehensive set computational pre-processing and analysis to resolve clonal substructure reconstruct genetic lineages tumors. We performed DNA 2977 from multiple spatial regions two liver metastasis 7365 three primary tumors with matched metastatic tissues. In metastases, CopyKit...
Abstract Our knowledge of copy number evolution during the expansion primary breast tumors is limited. To investigate this process, we developed a single-cell, single-molecule DNA sequencing method and performed analysis 13,808 single cells from six triple-negative cancers (TNBCs) two cancer cell lines. data shows that lines are comprised large milieu (17-26) subclones organized into few (4-8) major superclones. Phylogenetic mathematical modeling show was ongoing tumor, after initial...
Abstract BRCA2 germline mutation carriers have a lifetime risk of 72% for developing invasive breast cancer. Although has been implicated in double-stranded break repair, the role this genome evolution and maintaining instability during expansion primary tumor mass is not well understood. To investigate these questions, we developed novel method single-cell, single-molecule (SCSM) sequencing. SCSM uses Tn5 transposase to directly fragment ligate adapters PCR amplification, thereby omitting...
Abstract Ductal carcinoma in situ (DCIS) is the most common form of early stage breast cancer and frequently detected by mammography. Only 10% low-grade 30% high-grade DCIS patients will later present with an invasive carcinoma, making it difficult to determine which treat aggressively. Although often considered a precursor major question field whether subpopulations evolve directly from populations or independently. We hypothesize that tumor cells over extended period time ducts, generating...
Abstract Aneuploidy is a hallmark of breast cancer, but little known about how these complex genomic rearrangements evolve during tumor growth. To investigate this question, we developed Highly-Multiplexed Single Nucleus Sequencing (HM-SMS) method to profile genome-wide copy number in individual cells and compared multiple infer evolutionary lineages. We applied analyze thousands single from 12 triple-negative cancer patients 10 ductal-carcinoma-in-situ (DCIS) patients. Integer profiles were...
Abstract Intratumor heterogeneity is widely reported in many human tumors including breast cancer. However most studies to date have been limited genomic analysis of bulk tumor tissues and cytogenetic analysis. Here, we applied single cell copy number profiling delineate the clonal substructure triple-negative (ER-, PR-, Her2-) cancer (TNBC). We Single Nucleus Sequencing (SNS) profile 1000 cells from 11 TNBC patients. Our data show that profiles within are highly stable, belonging a few (N =...
Abstract Background: Triple negative breast cancer (TNBC) has a relative paucity of effective targeted therapies compared to other molecular subtypes, and with poor prognosis. Thus, new therapeutics are needed. ONC201 is first-in-class small molecule that induces caspase-mediated apoptosis in cancers. It recently showed efficacy pediatric glioma, harboring the potential be translated advanced cancer. Here we evaluated TNBC cell lines, investigated proteomic/genomic markers predict efficacy,...
Abstract High-throughput single cell transcriptomics analysis is widely used to study human tumors, however a major challenge distinguishing the stromal cells from malignant cancer cells, as well clonal substructure within tumors. To address this challenge, we developed an integrative Bayesian segmentation approach, COPYKAT estimate genomic copy numbers at 5MB resolution high-throughput RNA-seq data. We applied 39,709 16 tumors across 4 types, including premalignant and triple-negative...