- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Cancer Immunotherapy and Biomarkers
- Mercury impact and mitigation studies
- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Influenza Virus Research Studies
- Cancer, Lipids, and Metabolism
- Crystallization and Solubility Studies
- Geochemistry and Geologic Mapping
- Air Quality and Health Impacts
- Cancer, Hypoxia, and Metabolism
- Trace Elements in Health
- Metabolomics and Mass Spectrometry Studies
- HIV/AIDS Research and Interventions
- Bladder and Urothelial Cancer Treatments
- Image Retrieval and Classification Techniques
- DNA Repair Mechanisms
- Iron Metabolism and Disorders
- Heavy Metal Exposure and Toxicity
- HIV/AIDS drug development and treatment
Hauptman-Woodward Medical Research Institute
2020-2024
Clinic for Special Children
2024
University at Buffalo, State University of New York
2024
Eskenazi Health
2024
Eskenazi Health Foundation
2024
Roswell Park Comprehensive Cancer Center
2017-2020
Los Alamos National Laboratory
2017
UConn Health
2014-2017
University of Rochester
2010-2012
University of Minnesota, Duluth
2012
Cancer mutations generate novel (neo-)peptides recognised by T cells, but the determinants of recognition are not well characterised. The difference in predicted class I major histocompatibility complex (MHC-I) binding affinity between wild-type and corresponding mutant peptides (differential agretopicity index; DAI) may reflect clinically relevant cancer peptide immunogenicity. Our aim was to explore relationship DAI, measures immune infiltration patient outcomes advanced cancer.
Diffraction-based structural methods contribute a large fraction of the biomolecular models available, providing critical understanding macromolecular architecture. These require crystallization target molecule, which remains primary bottleneck in crystal-based structure determination. The National High-Throughput Crystallization Center at Hauptman-Woodward Medical Research Institute has focused on overcoming obstacles to through combination robotics-enabled high-throughput screening and...
Abstract Ewing sarcoma is the second most common bone malignancy in children and adolescents. In recent years, a large body of evidence has emerged that suggests tumors harbor amounts replication stress (RS). CDC7, also known as DDK (DBF4-dependent kinase), serine/threonine kinase involved diverse array cellular functions including regulation DNA initiation activation RS response. Due to DDK’s roles during replication, coupled with fact there an increased level within tumors, we hypothesized...
Microcrystal electron diffraction (MicroED) is an emerging structural technique in which submicron crystals are used to generate data for studies. Structures allow the study of molecular-level architecture and drive hypotheses about modes action, mechanisms, dynamics, interactions with other molecules. Combining cryoelectron microscopy (cryo-EM) instrumentation crystallographic techniques, MicroED has led three-dimensional models small molecules, peptides, proteins generated tremendous...
X-ray crystallography is the most commonly employed technique to discern macromolecular structures, but crucial step of crystallizing a protein into an ordered lattice amenable diffraction remains challenging. The crystallization biomolecules largely experimentally defined, and this process can be labor-intensive prohibitive researchers at resource-limited institutions. At National High-Throughput Crystallization (HTX) Center, highly reproducible methods have been implemented facilitate...
Ovarian cancer (OVC) is the most lethal of gynecological malignancies, with diagnosis often occurring during advanced stages disease. Moreover, a majority cases become refractory to chemotherapeutic approaches. Therefore, it important improve our understanding molecular dependencies underlying disease identify novel diagnostic and precision therapeutics for OVC. Cancer cells are known sequester iron, which can potentiate progression through mechanisms that have not yet been completely...
Oncogenic mutations in the kinase domain of B-Raf protein have long been associated with cancers involving MAPK pathway. One constitutive activating mutation B-Raf, V600E (valine to glutamate) replacement occurring adjacent a site threonine phosphorylation (T599) occurs many types cancer, and large percentage certain cancers, such as melanoma. Because ATP binding activity are both known alter physical behavior activation loop domain, this system is especially amenable comparative analyses...
Comparative functional analysis of the dynamic interactions between various
The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), developed for the World Health Organization (WHO), screens risks associated with use of tobacco, alcohol, seven categories drugs. Although ASSIST has acceptable psychometric properties, it is relatively long a screening test. This study was designed to identify subset questions from full instrument having comparable properties classification low-, moderate-, high-risk substance use.The used three data sets prior studies...
Nearly 90% of structural models in the Protein Data Bank (PDB), central resource worldwide for three-dimensional information, are currently derived from macromolecular crystallography (MX). A major bottleneck determining MX structures is finding conditions which a biomolecule will crystallize. Here, we present searchable database chemicals associated with successful crystallization experiments PDB. We use these data to examine relationship between protein secondary structure and average...
Imaging and pathology findings are used to analyze the capability of computed tomography (CT) distinguish between acute appendicitis radiological mimickers.A retrospective review 5861 patients undergoing abdominopelvic CT from 2000 2008 for suspicion was performed. Appendix diameter, surrounding inflammation, appendicolith, location were assessed. Only those cases included where underwent surgery on findings. Pathology specimens examined indicative identified. Statistical analysis performed...
The HIV-1 protease is one of several common key targets combination drug therapies for human immunodeficiency virus infection and acquired syndrome. During the progression disease, some individual patients acquire resistance due to mutational hotspots on viral proteins targeted by therapies. It has recently been discovered that drug-resistant mutations accumulate "flap region" protease, which a critical dynamic region involved in nonspecific polypeptide binding during invasion host cell. In...
A total of 1,513 individuals underwent CTLS. Downstream data, pre-test cardiac risk factors and CAC scores were available for 88.3% (1,336/1,513). The average length follow-up was 2.64 (SD ±0.72) years. There a 43 events, occurring in 1.55% (6/386) patients with mild CAC, 3.24% (11/339) moderate 8.90% (26/292) marked CAC. no events among reported (0/319). Using multivariable logistic modeling, the increased odds an initial event 2.56 (95% CI, 1.76-3.92, P<0.001) 6.57 3.10-15.4, 16.8...