A5031098985- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Treatments and Mutations
- Wound Healing and Treatments
- Epigenetics and DNA Methylation
- Phagocytosis and Immune Regulation
- Diabetic Foot Ulcer Assessment and Management
- Axon Guidance and Neuronal Signaling
- Photosynthetic Processes and Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Neuroblastoma Research and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Immune cells in cancer
- Glioma Diagnosis and Treatment
- Head and Neck Cancer Studies
- Retinal Development and Disorders
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Viral Infections and Vectors
- interferon and immune responses
- Mesenchymal stem cell research
- Immune responses and vaccinations
- Congenital heart defects research
- Muscle Physiology and Disorders
- Medical Education and Admissions
Yale University
2012-2025
Yale Cancer Center
2019
Universidad Nacional Autónoma de México
2007-2015
Association of American Medical Colleges
2012
Abstract Diabetic foot ulceration (DFU) is a devastating complication of diabetes whose pathogenesis remains incompletely understood. Here, we profile 174,962 single cells from the foot, forearm, and peripheral blood mononuclear using single-cell RNA sequencing. Our analysis shows enrichment unique population fibroblasts overexpressing MMP1, MMP3, MMP11, HIF1A, CHI3L1 , TNFAIP6 increased M1 macrophage polarization in DFU patients with healing wounds. Further, spatially separated samples same...
Resistance to DNA-damaging agents is a significant cause of treatment failure and poor outcomes in oncology. To identify unrecognized regulators cell survival we performed whole-genome CRISPR-Cas9 screen using with ionizing radiation as selective pressure, identified STING (stimulator interferon genes) an intrinsic regulator tumor survival. We show that regulates transcriptional program controls the generation reactive oxygen species (ROS), loss alters ROS homeostasis reduce DNA damage...
We compared faculty promotion rates by race/ethnicity across US academic medical centers.We used the Association of American Medical College's 1983 through 2000 roster data to estimate median institution-specific for assistant professor associate and full professor. In unadjusted analyses, we medians Hispanic Black with White using Wilcoxon rank sum test. between racial/ethnic groups stratified institutional characteristic (institution size, proportion minority faculty, women faculty) χ(2)...
Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC) commonly bear disruptive mutations in TP53, resulting treatment resistance. In these patients, direct targeting of p53 has not been successful, but synthetic lethal approaches have promise. Although Aurora A kinase (AURKA) is overexpressed an oncogenic driver, its inhibition only modest clinical effects HPV-negative HNSCC. We explored a novel combination AURKA WEE1 to overcome intrinsic resistance...
Apoptosis and clearance of apoptotic cells via efferocytosis are evolutionarily conserved processes that drive tissue repair. However, the mechanisms by which recognition regulate repair not fully understood. Here, we use single-cell RNA sequencing to provide a map cellular dynamics during early inflammation in mouse skin wounds. We find pathways receptors elevated fibroblasts immune cells, including resident Lyve1+ macrophages, inflammation. Interestingly, human diabetic foot wounds...
Abstract By analyzing the mechanisms that govern dopaminergic axon pathfinding from midbrain to striatum in embryonic rat brains, we identified neuroepithelial regions exert chemotropic effects on mesencephalic axons. Explants pretectum and showed an attractive effect, whereas those midhindbrain boundary, dorsal thalamus, ventral thalamus had no effect. Expression of semaphorin (Sema) 3C Sema3F Sema3A suggested a role for these guidance molecules pathfinding. When expressed HEK293 cell...
ABSTRACT Prognosis for patients with recurrent/metastatic (R/M) head and neck squamous cell cancer (HNSCC) remains poor. We hypothesized that the addition of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to standard therapy would improve responses by inhibiting nuclear translocation EGFR designed a phase 2 trial chemotherapy, cetuximab erlotinib in R/M HNSCC. 24 were enrolled treated carboplatin, paclitaxel administered 21-day cycles. Erlotinib was added cycle 2....
Prognosis for patients with recurrent/metastatic (R/M) head and neck squamous cell cancer (HNSCC) remains poor. We hypothesized that the addition of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to standard therapy would improve responses by inhibiting nuclear translocation EGFR designed a phase 2 trial chemotherapy, cetuximab, erlotinib in R/M HNSCC. A 24 were enrolled treated carboplatin, paclitaxel, cetuximab administered 21-day cycles. Erlotinib was added...
Wound repair requires the coordination of multiple cell types including immune cells and tissue resident to coordinate healing return function. Diabetic foot ulceration is a type chronic wound that impacts over 4 million patients in US 7 worldwide (Edmonds et al., 2021). Yet, cellular molecular mechanisms go awry these wounds are not fully understood. Here, by profiling ulcers from non-diabetic (NDFUs) diabetic (DFUs) using single-cell RNA sequencing, we find DFUs display transcription...
The mamillary body (MM) is a group of hypothalamic nuclei related to memory and spatial navigation that interconnects hippocampal, thalamic, tegmental regions. Here we demonstrate Lhx5, LIM-HD domain transcription factor expressed early in the developing posterior hypothalamus, required for generation MM its derived tracts. markers Foxb1, Sim2 Lhx1 are absent Lhx5 knock-out mice from embryonic stages, suggesting abnormal specification this region. This was supported by absence Nkx2.1...
Apoptosis and clearance of apoptotic cells via efferocytosis are evolutionarily conserved processes that drive tissue repair. However, the mechanisms by which recognition regulate repair not fully understood. Here, we use single-cell RNA sequencing to provide a map cellular dynamics during early inflammation in mouse skin wounds. We find pathways receptors elevated fibroblasts immune cells, including resident Lyve1 + macrophages, inflammation. Interestingly, human diabetic foot wounds...
Abstract Information from both sides of the brain is integrated by axons that project across midline central nervous system via numerous commissures present at all axial levels. Despite accumulated experimental evidence, questions remain regarding formation in presence strong repulsive signals ventral midline. Studies invertebrates suggest interaction between homologous specific decussating neurons contributes to efficient crossing, but such evidence lacking vertebrate systems. We performed...
Abstract To understand the diabetic wound healing microenvironment, we profiled 174,962 single cells from foot, forearm, and PBMCs using single-cell RNA sequencing (scRNASeq) approach. Our analysis shows enrichment of a unique population fibroblasts overexpressing MMP1, MMP3, MMP11, HIF1A, CHI3L1 , TNFAIP6 genes M1 macrophage polarization in DFU patients with wounds. Further, scRNASeq spatially separated samples same patient spatial transcriptomics (ST) revealed preferential localization...
e17520 Background: No biomarker of C resistance has been identified in HNSCC. PTEN loss is present approximately 30% Biomarker analysis the E5397 study suggested that addition to cisplatin R/M HNSCC improves PFS high/PIK3CA wild type patients but not those with or PIK3CA mutation. We hypothesized testing may aid patient (pt.) selection for therapy Methods: MCC15780 was a phase II randomized trial plus sorafenib placebo 52/56 pts. this received C. using AQUA as previously described performed...
e14105 Background: Aurora Kinase A (AURKA) is overexpressed in HNSCC, and correlates with poor prognosis. It has been identified as a potential therapeutic target, yet the response rate for AURKA inhibitor MLN8237 only 9% treatment refractory HNSCC. We hypothesized that although inhibitors lead to defective spindle assembly, they may also reduce mitotic entry, undermining cytotoxic effect. predicted adding WEE1 an would mitigate this effect enhance cell death Methods: Cell viability assays...
<p>Supplementary Figure S1. Overview of the identified mutations in UNC7 HNSCC cell line by whole exome sequencing.</p>
<p>Supplementary Figure S2 related to 3. Representative image of cell cycle distribution FaDu and UNC7 cells determined by FACS analysis. Cells were treated with vehicle, adavosertib (AZD1775, 500 nM), alisertib (MLN8237, 250 or the combination for 8 24 hours followed PI staining. Cell was assessed analysis analyzed using FlowJo software.</p>
<p>Supplementary figure legends</p>
<p>Supplementary Figure S5 related to 5H. (A) Heat map QIF of pCDK1 expression intensity in FaDu xenograft mice treated with (a) vehicle, (b) alisertib, (c) adavosertib or (d) alisertib+adavosertib. Scores range from very low (purple) high (yellow). Black squares represent FOVs which scores were not calculated due presence artifacts, lack tumor, etc. (B) Graph depicts Mean {plus minus} SD nuclei tumor. The is significantly reduced and alisertib+adavosertib FaDu-xenografted mice....
<p>Supplementary Figure S4 related to 5D-F. (A) Individual tumor volume changes in Detroit 562-xenografted mice treated with vehicle, adavosertib (30 mg/kg, daily, p.o.), alisertib or the combinations of adavosertib. Tumor all belonged this study was shown bottom panel (n = 6 per group). Significant differences between combination and single drug alone are shown. (B) Body weight (g) monitored every other day. Graphs depict Mean {plus minus} SEM.</p>
<p>Supplementary Figure S3 related to 5A-C. (A) Individual tumor volume changes in FaDu-xenografted mice treated with vehicle, adavosertib (30 mg/kg or 90 mg/kg, daily, p.o.), alisertib the combinations of either mg/kg) (90 mg/kg). Tumor all belonged this study was shown bottom panel (n = 8-9 per group). Significant differences between combination and single drug alone are shown. (B) Body weight (g) monitored twice a week. Humane endpoint considered when reached 1,000 mm3 following...
<div>AbstractPurpose:<p>Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC) commonly bear disruptive mutations in <i>TP53</i>, resulting treatment resistance. In these patients, direct targeting of p53 has not been successful, but synthetic lethal approaches have promise. Although Aurora A kinase (AURKA) is overexpressed an oncogenic driver, its inhibition only modest clinical effects HPV-negative HNSCC. We explored a novel combination...
<div>AbstractPurpose:<p>Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC) commonly bear disruptive mutations in <i>TP53</i>, resulting treatment resistance. In these patients, direct targeting of p53 has not been successful, but synthetic lethal approaches have promise. Although Aurora A kinase (AURKA) is overexpressed an oncogenic driver, its inhibition only modest clinical effects HPV-negative HNSCC. We explored a novel combination...
<p>Supplementary figure legends</p>