A5008815542- CAR-T cell therapy research
- Neuroblastoma Research and Treatments
- Sarcoma Diagnosis and Treatment
- Erythrocyte Function and Pathophysiology
- Epigenetics and DNA Methylation
- Acute Lymphoblastic Leukemia research
- Hemoglobinopathies and Related Disorders
- Peptidase Inhibition and Analysis
- Virus-based gene therapy research
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Blood groups and transfusion
- Immunotherapy and Immune Responses
- RNA regulation and disease
- Metabolism and Genetic Disorders
- Insect behavior and control techniques
- RNA modifications and cancer
- Chronic Lymphocytic Leukemia Research
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Cancer-related gene regulation
- Radiopharmaceutical Chemistry and Applications
- Iron Metabolism and Disorders
- Hemoglobin structure and function
- Nuclear Structure and Function
RTI International
2019-2025
Genomics (United Kingdom)
2025
University of North Carolina at Chapel Hill
2011-2019
University of Pittsburgh
2009
Abstract Purpose: Patients with relapsed pediatric solid malignancies have few therapeutic options, and many of these patients die their disease. B7-H3 is an immune checkpoint protein encoded by the CD276 gene that overexpressed in cancers. Here, we investigate activity B7-H3–targeting antibody–drug conjugate (ADC) m276-SL-PBD malignancy patient-derived (PDX) cell line–derived xenograft (CDX) models. Experimental Design: expression was quantified RNA sequencing IHC on PDX microarrays. We...
Antibody-drug conjugates (ADCs) combining monoclonal antibodies with cytotoxic payloads are a rapidly emerging class of immune-based therapeutics the potential to improve treatment cancer, including children relapse/refractory acute lymphoblastic leukemia (ALL). CD123, α subunit interleukin-3 receptor, is overexpressed in ALL and therapeutic target. Here, we show that pivekimab sunirine (PVEK), recently developed ADC comprising CD123-targeting antibody, G4723A, payload, DGN549, was highly...
Sirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated aging metabolism regulation. Targeted sequencing of SIRT6 locus population 450 Ashkenazi Jewish (AJ) centenarians 550 AJ individuals without family history exceptional longevity identified enrichment allele containing two linked substitutions (N308K/A313S) compared with control individuals. Characterization this (centSIRT6) demonstrated it to be stronger...
The consequences of hybridization are varied, ranging from the origin new lineages, introgression some genes between species, to extinction one hybridizing species. We generated replicate admixed populations two pairs sister species
Abstract Immunoconjugates targeting cell-surface antigens have demonstrated clinical activity to enable regulatory approval in several solid and hematologic malignancies. We hypothesize that a rigorous comprehensive surfaceome profiling approach identify osteosarcoma-specific can similarly development of effective therapeutics this disease. Herein, we describe an integrated proteomic transcriptomic proteins are highly expressed osteosarcoma but minimally on normal tissues. Using approach,...
Red blood cell (RBC) metabolic reprogramming upon exposure to high altitude contributes physiological human adaptations hypoxia, a multifaceted process critical health and disease. To delve into the molecular underpinnings of this phenomenon, first, we performed multi-omics analysis RBCs from six lowlanders after high-altitude with longitudinal sampling at baseline, ascent 5,100 m descent sea level. Results highlighted an association between erythrocyte levels 2,3-bisphosphoglycerate (BPG),...
A metamorphosis from rosette to inflorescence in many annuals shifts photosynthetic tissue a two-dimensional array the soil boundary layer during cool months three-dimensional structure troposphere as spring progresses. We propose that this shift allows escape both self-shading and an increasingly stressful microclimate, permitting continued increases growth. As first step exploring hypothesis, we compared lifetime C gain, water loss, instantaneous use efficiency (WUE) of five Arabidopsis...
Abstract Background Storage of packed red blood cells (RBCs) for transfusion leads to biochemical and morphological changes, increasing hemolysis risk. Urate levels in bags at donation contribute the molecular heterogeneity hemolytic propensity stored RBCs. However, studies date have been underpowered investigate scale contribution donor demographics genetics urate across donations. Study Design Methods were measured 13,091 RBC units from REDS study. Characteristics tested included...
In mid-2020, the Centers for Research in Emerging Infectious Diseases (CREID) Network was established to address critical gaps research expertise and capacity emerging re-emerging infectious diseases (EIDs). As during COVID-19 pandemic, most of Network’s centers initially focused on SARS-CoV-2 research. By end 2021, leadership realized that it had a blind spot with regards their sites’ overall capacities stakeholder connections. To foster more meaningful deeper levels coordination...
Abstract Introduction: Vobra duo, a duocarmycin-based humanized ADC (drug-to-antibody ratio is ∼2.7) targeting B7-H3, shows robust in vivo activity against range of adult cancer models, and favorable pharmacokinetic safety profile cynomolgus monkeys. Initial results from the single agent phase 1 clinical trial vobra duo (NCT03729596) showed manageable side effects promising objective response rates metastatic castration-resistant prostate cancer. B7-H3 highly expressed pediatric solid...
Many insects feed on only one or a few types of host. These host specialists often evolve preference for chemical cues emanating from their and develop mechanisms circumventing host's defenses. Adaptations like these are central to evolutionary biology, yet our understanding genetics remains incomplete. Drosophila sechellia, an emerging model the specialization, is island endemic that has adapted toxins present in fruit its plant, Morinda citrifolia. Its sibling species, D. simulans, many...
Summary Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and the bank. Here, we leveraged a diversity outbred mouse population to map genetic drivers of fresh/stored RBC extravascular upon storage transfusion 350 mice. We identify ferrireductase Steap3 as critical regulator ferroptosis-like process lipid peroxidation. polymorphisms were associated with iron content, vitro hemolysis, both mice 13,091 donors from Recipient Epidemiology Donor evaluation Study. Using...
Finding the genes underlying complex traits is difficult. We show that new sequencing technology combined with traditional genetic techniques can efficiently identify regions a and quantitative behavioral trait. As proof of concept we used phenotype-based introgression to backcross loci control innate food preference in Drosophila simulans into genomic background D. sechellia, which expresses opposite preference. successfully mapped small mapping population (30 flies) whole-genome...
Mature red blood cells (RBCs) lack mitochondria, and thus exclusively rely on glycolysis to generate adenosine triphosphate (ATP) during aging in vivo or storage the bank. Here we leveraged 13,029 volunteers from Recipient Epidemiology Donor Evaluation Study identify an association between end-of-storage levels of glycolytic metabolites donor age, sex, ancestry-specific genetic polymorphisms regions encoding phosphofructokinase 1, platelet (detected mature RBCs), hexokinase ADP-ribosyl...
Abstract The Pediatric Preclinical Testing Program (PPTP) previously reported the activity of EZH2 inhibitor tazemetostat (EPZ6438) against xenograft models rhabdoid tumors. Here, we determined whether an enhanced effect standard care chemotherapeutic agents: irinotecan, vincristine, and cyclophosphamide. EPZ011989 significantly prolonged time to event in all six studied but did not induce tumor regression. addition agents improved at least one model for each studied, although this was...
Abstract Increasing global life expectancy motivates investigations of molecular mechanisms aging and age‐related diseases. This study examines age‐associated changes in red blood cells (RBCs), the most numerous host cell humans. Four cohorts, including healthy individuals patients with sickle disease, were analyzed to define age‐dependent RBC metabolism. Over 15,700 specimens from 13,757 humans examined, a major expansion over previous studies RBCs aging. Multi‐omics approaches identified...