A5036687398- Protein Kinase Regulation and GTPase Signaling
- Protein Structure and Dynamics
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Advanced MRI Techniques and Applications
- Molecular spectroscopy and chirality
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- T-cell and B-cell Immunology
- Radiomics and Machine Learning in Medical Imaging
- Thyroid Disorders and Treatments
- Gene expression and cancer classification
- Head and Neck Cancer Studies
- Muscle metabolism and nutrition
- Cancer Genomics and Diagnostics
- Scientific Computing and Data Management
- Genetics, Bioinformatics, and Biomedical Research
- Microbial Natural Products and Biosynthesis
- Immune Cell Function and Interaction
- Lung Cancer Research Studies
- Machine Learning in Bioinformatics
- Privacy, Security, and Data Protection
- Cell Image Analysis Techniques
- Endoplasmic Reticulum Stress and Disease
Fox Chase Cancer Center
2018-2024
Memorial Sloan Kettering Cancer Center
2024
Drexel University
2017-2023
Indiana University Health
2023
Indiana University – Purdue University Indianapolis
2023
Monmouth University
2015-2017
Monmouth Medical Center
2016
St. George's University
2016
University of Pittsburgh
1980
Head and neck squamous cell carcinoma (HNSCC) is a frequently devastating cancer that affects more than half million people annually worldwide. Although some cases arise from infection with human papillomavirus (HPV), HPV-negative HNSCC common, associated worse outcome. Advanced may be treated surgery, chemoradiation, targeted therapy, or immune checkpoint inhibition (ICI). There considerable need for predictive biomarkers these treatments. Defects in DNA repair capacity loss of cell-cycle...
The digitization of health records and growing availability tumour DNA sequencing provide an opportunity to study the determinants cancer outcomes with unprecedented richness. Patient data are often stored in unstructured text siloed datasets. Here we combine natural language processing annotations1,2 structured medication, patient-reported demographic, registry genomic from 24,950 patients at Memorial Sloan Kettering Cancer Center generate a clinicogenomic, harmonized oncologic real-world...
Abstract Loss of expression or activity the tumor suppressor PTEN acts similarly to an activating mutation in oncogene PIK3CA elevating intracellular levels phosphatidylinositol (3,4,5)-trisphosphate (PIP3), inducing signaling by AKT and other pro-tumorigenic proteins. Here, we analyze sequence data for 34,129 colorectal cancer (CRC) patients, capturing 3,434 mutations. We identify specific patterns associated with microsatellite stability/instability (MSS/MSI), mutational burden (TMB),...
Mutations in RAS isoforms (KRAS, NRAS, and HRAS) are among the most frequent oncogenic alterations many cancers, making these proteins high priority therapeutic targets. Effectively targeting requires an exact understanding of their active, inactive, druggable conformations. However, there is no structural catalog conformations to guide or examining impact mutations. Here we present expanded classification based on analyses catalytic switch 1 (SW1) 2 (SW2) loops. From 721 human KRAS, HRAS...
Streamlit is an open-source Python coding framework for building web-applications or "web-apps" and now being used by researchers to share large data sets from published studies other resources. Here we present Stmol, easy-to-use component rendering interactive 3D molecular visualizations of protein ligand structures within web-apps. Stmol can render with just a few lines code utilizing popular visualization libraries, currently Py3DMol Speck. On the user-end, does not require expertise...
Problem Little is known about how infection and the response to inflammation affect micro RNA (mi ) profile of male reproductive tract. We hypothesized that expression inflammatory‐related mi s would be altered following immune activation rat testis. Method study Testis total was purified from Sprague‐Dawley rats 3 or 6 hours after receiving a 5 mg/kg intraperitoneal injection bacterial lipopolysaccharide ( LPS examined by qPCR using an 84‐panel array. Results Five showed greater than...
Cryo-EM structure of TFIIK provides insight into CTD phosphorylation RNA polymerase II in the preinitiation-Mediator complex.
Abstract Antibody complementarity determining regions (CDRs) are loops within antibodies responsible for engaging antigens during the immune response and in antibody therapeutics laboratory reagents. Since 1980s, conformations of hypervariable CDRs have been structurally classified into a number “canonical conformations” by Chothia, Lesk, Thornton, others. In 2011 (North et al, J Mol Biol. 2011), we produced quantitative clustering approximately 300 structures each CDR based on their length,...
Abstract T cell receptor (TCR) signaling regulates important developmental transitions, partly through induction of the E protein antagonist, Id3. Although normal γδ development depends on Id3, Id3 deficiency produces different phenotypes in distinct subsets. Here, we show that impairs Vγ3 + subset, while markedly enhancing NKγδT cells expressing invariant Vγ1Vδ6.3 TCR. These effects result from regulating both generation TCR and its capacity to support development. Indeed, Trav15 segment,...
A 23-year-old woman had silent thyrotoxic thyroiditis and chronic adrenocortical insufficiency (Addison's disease). Recent evidence suggests that is an autoimmune disease characterized by lymphocytic infiltration of the thyroid transient hyperthyroidism, followed occasionally hypothyroidism eventual recovery. This case would seem to expand spectrum diseases (Graves' disease, [Hashimoto's] thyroiditis, hypothyroidism) associated with insufficiency.
6552 Background: The tumor suppressors TP53 and CDKN2A are commonly mutated or lost in HNSCC, impairing G1 checkpoints. This reduces ability to repair DNA damage arising from hypoxia, replication stress, mutagen exposure, thus increasing TMB, a potential predictive biomarker for immunotherapy benefit. mutations can be classified as loss-of-function (LOF) with without dominant negative (DNE) activity, gain-of-function (GOF) benign. We investigated whether specific categories of mutation were...
Schwannomas are benign, often asymptomatic, slow-growing tumors that originate from Schwann cells of the neural sheath. Although H. Pylori has been associated with gastric adenocarcinoma, there never a recorded association schwannoma formation. We present 64-year-old woman who underwent laparoscopic partial wedge gastrectomy for an incidentally discovered mass. Histologic examination was consistent schwannoma; however, chronic inflammation microorganisms morphologically also present. This...
Epithelioid angiosarcoma is a rare high-grade tumor with irregular vascular morphology. We report an unusual case of intra-abdominal epithelioid affecting the omentum and peritoneal surfaces resulting in significant hemorrhagic inflammatory changes. As other cases this patient had previously undergone radiation treatment for history cervical cancer.
ABSTRACT T cell receptor (TCR) signals regulate important developmental transitions through induction of the E protein antagonist, Id3; however, Id3-deficiency produces paradoxical effects on γδ subsets. Here, we show here that attenuates development Vγ3-expressing cells, while markedly enhancing Vγ1Vδ6.3-expressing NKγδT cells. does so by regulating both generation stereotypic Vγ1Vδ6.3 TCR expressed cells and its capacity to support development. Indeed, determined Trav15 segment, which...
ABSTRACT For many human cancers and tumor-associated diseases, mutations in the RAS isoforms (KRAS, NRAS, HRAS) are most common oncogenic alterations, making these proteins high-priority therapeutic targets. Effectively targeting requires an exact understanding of their active, inactive, druggable conformations. However, there is no structure-guided catalogue conformations to guide or examining structural impact mutations. We present expanded classification based on analyzing catalytic...
ABSTRACT Oncogenic KRAS mutations occur in approximately 30% of lung adenocarcinoma. Despite several decades effort, oncogenic KRAS-driven cancer remains difficult to treat, and our understanding the positive negative regulators RAS signaling is incomplete. To uncover functional impact diverse KRAS-interacting proteins on growth vivo , we used multiplexed somatic CRISPR/Cas9-based genome editing genetically engineered mouse models with tumor barcoding high-throughput barcode sequencing....
Supplementary Data from Delineating the RAS Conformational Landscape
<div>Abstract<p>Mutations in RAS isoforms (KRAS, NRAS, and HRAS) are among the most frequent oncogenic alterations many cancers, making these proteins high priority therapeutic targets. Effectively targeting requires an exact understanding of their active, inactive, druggable conformations. However, there is no structural catalog conformations to guide or examining impact mutations. Here we present expanded classification based on analyses catalytic switch 1 (SW1) 2 (SW2) loops....