Laura Richardson
A5049600369- Computational Drug Discovery Methods
- Biosimilars and Bioanalytical Methods
- Health Systems, Economic Evaluations, Quality of Life
- Sperm and Testicular Function
- Single-cell and spatial transcriptomics
- Neonatal Respiratory Health Research
- DNA Repair Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Bioinformatics and Genomic Networks
- Congenital heart defects research
- COVID-19 Clinical Research Studies
- Infant Nutrition and Health
- Birth, Development, and Health
- Congenital Diaphragmatic Hernia Studies
- Cell Image Analysis Techniques
- Reproductive Biology and Fertility
- Cancer Genomics and Diagnostics
- Gene expression and cancer classification
- Testicular diseases and treatments
- Cell Adhesion Molecules Research
- Rabbits: Nutrition, Reproduction, Health
- Advanced Breast Cancer Therapies
- Nasal Surgery and Airway Studies
- Mathematical Biology Tumor Growth
- Urologic and reproductive health conditions
Wellcome Sanger Institute
2015-2025
University of Akron
2019
Marshall University
2005-2014
University of California, Los Angeles
2011-2012
University of Tennessee at Knoxville
1998-2004
Florida International University
1998-2002
Georgetown University Medical Center
1983-1998
Georgetown University
1983-1998
National Foundation for Cancer Research
1995
Sanford Burnham Prebys Medical Discovery Institute
1995
Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature cancer. Using this information to guide development and application therapies in clinic is challenging. Here, we report how cancer-driven alterations identified 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, gene expression) can be mapped onto 1,001 molecularly annotated human cell lines correlated with sensitivity 265 drugs. We find...
Abstract Combinations of anti-cancer drugs can overcome resistance and provide new treatments 1,2 . The number possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active the tissues molecular contexts in which they are most effective accelerate development combination treatments. Here we evaluate potency efficacy 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast,...
It is not fully understood why COVID-19 typically milder in children
The function of a cell is defined by its intrinsic characteristics and niche: the tissue microenvironment in which it dwells. Here we combine single-cell spatial transcriptomics data to discover cellular niches within eight regions human heart. We map cells microanatomical locations integrate knowledge-based unsupervised structural annotations. also profile cardiac conduction system
The proteome provides unique insights into disease biology beyond the genome and transcriptome. A lack of large proteomic datasets has restricted identification new cancer biomarkers. Here, proteomes 949 cell lines across 28 tissue types are analyzed by mass spectrometry. Deploying a workflow to quantify 8,498 proteins, these data capture evidence cell-type post-transcriptional modifications. Integrating multi-omics, drug response, CRISPR-Cas9 gene essentiality screens with deep...
We present a multiomic cell atlas of human lung development that combines single-cell RNA and ATAC sequencing, high-throughput spatial transcriptomics, imaging. Coupling methods with analysis has allowed comprehensive cellular survey the epithelial, mesenchymal, endothelial, erythrocyte/leukocyte compartments from 5–22 post-conception weeks. identify previously uncharacterized states in all compartments. These include developmental-specific secretory progenitors subtype neuroendocrine...
The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the dynamics early cellular responses to this disease remains limited
Abstract Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in people over 85 years age remains high. Here we investigate differences cellular landscape and function paediatric (<12 years), adult (30–50 years) older (>70 ex vivo cultured nasal epithelial cells response infection SARS-CoV-2. We show that cell tropism SARS-CoV-2, expression ACE2 TMPRSS2 subtypes, differ between groups. While ciliated are viral replication centres...
Abstract Oncology drug combinations can improve therapeutic responses and increase treatment options for patients. The number of possible is vast be context-specific. Systematic screens identify clinically relevant, actionable in defined patient subtypes. We present data 109 anticancer from AstraZeneca's oncology small molecule portfolio screened 755 pan-cancer cell lines. Combinations were a 7 × concentration matrix, with more than 4 million measurements sensitivity, producing an...
Human embryonic bone and joint formation is determined by coordinated differentiation of progenitors in the nascent skeleton. The cell states, epigenetic processes key regulatory factors that underlie lineage commitment these cells remain elusive. Here we applied paired transcriptional profiling approximately 336,000 nucleus droplets spatial transcriptomics to establish a multi-omic atlas human cranium development between 5 11 weeks after conception. Using combined modelling data,...
Abstract Developmental dynamics encompass both the specification of cell types and their spatial organisation into multicellular niches. Here we harness power single-cell multiomics to unravel embryonic foetal cardiac tissue niches, which lead development a new tool, TissueTypist. We reveal that cardiac-resident macrophages likely originate from yolk sac, forming heterogeneous subsets. CX3CR1 + with microglia-like profile localise in sinoatrial node, may contribute axon guidance for...
Abstract T cells develop from circulating precursor cells, which enter the thymus and migrate through specialized subcompartments that support their maturation selection 1 . In humans, this process starts in early fetal development is highly active until thymic involution adolescence. To map microanatomical underpinnings of pre- postnatal stages, we established a quantitative morphological framework for thymus—the Cortico-Medullary Axis—and used it to perform spatially resolved analysis....
Ewing’s sarcoma is a malignant pediatric bone tumor with poor prognosis for patients metastatic or recurrent disease. cells are acutely hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition and this being evaluated in clinical trials, although the mechanism of hypersensitivity has not been directly addressed. PARP inhibitors have efficacy tumors BRCA1/2 mutations, which confer deficiency DNA double-strand break (DSB) repair by homologous recombination (HR). This drives dependence...
Abstract The human heart and adjoining great vessels consist of multiple cell types vital for life, yet many remain uncharacterised molecularly during development. Here, we performed a high-resolution profiling the first second trimesters, defining 63 with distinct identity location-specific signatures. We reveal previously unreported types, including pericardium ductus arteriosus. At ventricles, identified signatures involved in establishing trabeculation-compaction right-left axes...
Both Sertoli and myoid cells have been shown to be required for the appropriate deposition of basement membrane in testis. We sought define pattern gene expression peritubular vitro order begin understand regulatory mechanisms involved synthesis. cultured alone or together were examined synthesis components. Immunocytochemical localization demonstrated that produced laminin collagen IV, but not fibronectin, while all three proteins. In Sertoli:myoid cocultures, a sequential components into...
Abstract The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics surge diseases 1,2 has fuelled efforts to catalogue cells constituting tissues health disease 3 . Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy development adulthood. We uniformly processed 385 samples from 189 controls using newly developed automated quality control approach (scAutoQC),...
Bclw is a death-protecting member of the Bcl2 family apoptosis-regulating proteins. Mice that are mutant for display progressive and nearly complete testicular degeneration. We performed morphometric evaluation histopathology in Bclw-deficient male mice between 9 days postnatal (p9) through 1 yr age. Germ cell loss began by p22, with only few germ cells remaining beyond 7 mo A block to elongated spermatid development at step 13 occurred during first wave spermatogenesis, whereas other types...
T cells develop from circulating precursors, which enter the thymus and migrate throughout specialised sub-compartments to support maturation selection. This process starts already in early fetal development is highly active until involution of adolescence. To map micro-anatomical underpinnings this pre- vs. post-natal states, we undertook a spatially resolved analysis established new quantitative morphological framework for thymus, Cortico-Medullary Axis. Using axis conjunction with...
Abstract This study explores the in vitro modulation of lipid‐filled phenotype lipid interstitial cell (LIC) isolated from developing rat lung. Isolated LIC lose their cytoplasmic droplets when cultured fetal bovine serum (FBS) but retain potential for storage, since they rapidly reaccumulate subcultured neonatal (NRS) and to a lesser extent adult (ARS). The return state may not represent differentiation, it occurs presence bromodeoxy‐uridine. NRS contains twice free fatty acids (FFA) FBS...
Combining drugs can enhance their clinical efficacy, but the number of possible combinations and inter-tumor heterogeneity make identifying effective challenging, while existing approaches often overlook clinically relevant activity. We screen one largest cell line panels (N = 757) with 51 identify responses at level individual lines tissue populations. establish three response classes to model cellular effects beyond monotherapy: synergy, Bliss additivity, independent drug action (IDA)....
Didactic lessons are only one part of the multimodal teaching strategies used in gross anatomy courses today. Increased emphasis is placed on providing more opportunities for students to develop lifelong learning and critical thinking skills during medical training. In a pilot program designed promote engaged independent anatomy, self‐study modules were introduced supplement human instruction at Joan C. Edwards School Medicine Marshall University. Modules use three‐dimensional constructs...