A5031962631- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Retinoids in leukemia and cellular processes
- Cell death mechanisms and regulation
- Monoclonal and Polyclonal Antibodies Research
- Acute Lymphoblastic Leukemia research
- Histone Deacetylase Inhibitors Research
- RNA Interference and Gene Delivery
- Intensive Care Unit Cognitive Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer therapeutics and mechanisms
- Renal Transplantation Outcomes and Treatments
- Erythrocyte Function and Pathophysiology
- Nanoparticle-Based Drug Delivery
- Multiple Myeloma Research and Treatments
- Protein purification and stability
- Advanced biosensing and bioanalysis techniques
- Music Therapy and Health
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Cytomegalovirus and herpesvirus research
- Neuroblastoma Research and Treatments
- Lymphoma Diagnosis and Treatment
- Patient Safety and Medication Errors
- Chronic Lymphocytic Leukemia Research
AstraZeneca (United States)
2025
Cincinnati Children's Hospital Medical Center
2019-2023
Wayne State University
2013-2016
Michigan United
2013
Abstract Purpose: To investigate the molecular mechanism underlying intrinsic resistance to ABT-199. Experimental Design: Western blots and real-time RT-PCR were used determine levels of Mcl-1 after ABT-199 treatment alone or in combination with cytarabine daunorubicin. Immunoprecipitation Bim effect on their interactions Bcl-2 family members. Lentiviral short hairpin RNA knockdown CRISPR confirm role JC-1 assays flow cytometry drug-induced apoptosis. Results: from ABT-199–treated cell lines...
Bulk analysis of renal allograft biopsies (rBx) identified RNA transcripts associated with acute cellular rejection (ACR); however, these lacked context critical to mechanistic understanding how occurs despite immunosuppression (IS). We performed combined single-cell transcriptomic and TCR-α/β sequencing on rBx from patients ACR under differing IS drugs: tacrolimus, iscalimab, belatacept. found distinct CD8+ T cell phenotypes (e.g., effector, memory, exhausted) depending upon type,...
Acute myeloid leukemia (AML) remains a challenging disease to treat and urgently requires new therapies improve its treatment outcome. In this study, we investigated the molecular mechanisms underlying cooperative antileukemic activities of panobinostat cytarabine or daunorubicin (DNR) in AML cell lines diagnostic blast samples vitro vivo. Panobinostat suppressed expression BRCA1, CHK1, RAD51 cells dose-dependent manner. Further, significantly increased cytarabine- DNR-induced DNA...
Prognostic biomarkers for pediatric septic shock are conserved in a murine model of sepsis and accelerate testing precision medicine strategies.
Acute myeloid leukemia (AML) remains a difficult disease to treat and requires new therapies improve treatment outcome. Wee1 inhibitors have been used prevent activation of the G2 cell cycle checkpoint, thus enhancing antitumor activity DNA damaging agents. In this study, we investigated MK-1775 in AML lines diagnostic blast samples identify sensitive subtypes as well possible mechanisms resistance. vitro cytotoxicities blasts were measured using MTT assays. The effects on progression...
Highly concentrated antibody solutions are necessary for developing subcutaneous injections but often exhibit high viscosities, posing challenges in antibody-drug development, manufacturing, and administration. Previous computational models were only limited to a few dozen data points training, bottleneck generalizability. In this study, we measured the viscosity of panel 229 monoclonal antibodies (mAbs) develop predictive concentration mAb screening. We developed DeepViscosity, consisting...
High-risk neuroblastoma remains a therapeutic challenge with long-term survival rate of less than 40%. Therefore, new agents are urgently needed to overcome chemotherapy resistance so as improve the treatment outcome this deadly disease. Histone deacetylase (HDAC) inhibitors (HDACIs) represent novel class anticancer drugs. Recent studies demonstrated that HDACIs can down-regulate CHK1 pathway by which cancer cells develop conventional This prompted our hypothesis combining DNA damaging...
Background Most Down syndrome children with acute myeloid leukemia (DS-AML) have an overall excellent prognosis, however, patients who suffer induction failure or relapse, extremely poor prognosis. Hence, new therapies need to be developed for this subgroup of DS-AML patients. One therapeutic approach is preventing cell cycle checkpoint activation by inhibiting the upstream kinase wee1 first-in-class inhibitor MK-1775 in combination standard genotoxic agent cytarabine (AraC). Procedure Using...
Resistance to cytarabine and anthracycline-based chemotherapy is a major cause of treatment failure for acute myeloid leukemia (AML) patients. Overexpression Bcl-2, Bcl-xL, and/or Mcl-1 has been associated with chemoresistance in AML cell lines poor clinical outcome Thus, inhibitors anti-apoptotic Bcl-2 family proteins could be novel therapeutic agents. In this study, we investigated how clinically achievable concentrations obatoclax, pan-Bcl-2 inhibitor, potentiate the antileukemic activity...
It has been previously shown that acute myeloid leukemia (AML) patients with higher levels of GATA1 expression have poorer outcomes. Furthermore, pediatric Down syndrome (DS) megakaryocytic (AMKL), whose blast cells almost universally harbor somatic mutations in exon 2 the transcription factor gene GATA1, demonstrate increased overall survival relative to non-DS patients, suggesting a potential role for chemotherapy response. In this study, we confirmed amongst transcripts were significantly...
Despite studies indicating a high rate of overuse, electrolyte testing remains common in pediatric inpatient care. Frequently repeated tests often return normal results and can lead to patient harm increased cost. We aimed reduce within hospital medicine service by >25% 6 months.We conducted an improvement project which we targeted teams at large academic children's system using the Model for Improvement. Interventions included standardizing communication about plan education costs risks...
Piperacillin/tazobactam, a commonly used antibiotic, is associated with acute kidney injury (AKI). The relationship between piperacillin concentrations and AKI remains unknown.Estimate exposures in critically ill children young adults administered piperacillin/tazobactam to identify clinical factors piperacillin-associated AKI.We assessed pharmacokinetics 107 patients admitted the paediatric ICU who received at least one dose of piperacillin/tazobactam. Piperacillin AUC, highest peak (Cmax)...
In this study we sought to identify genetic factors associated with the presenting white blood cell (WBC) count in B-precursor acute lymphoblastic leukemia (BP-ALL). Using ETV6-RUNX1-positive BP-ALL patient samples, a homogeneous subtype, identified 16 differentially expressed genes based on WBC (< 50,000/cumm vs > 50,000). We further confirmed that IL1R1, BCAR3, KCNH2, PIR, and ZDHHC23 were larger cohort of ETV6-RUNX1-negative samples. Statistical analysis demonstrated expression levels...
Bulk analysis of renal allograft biopsies (rBx) identified RNA transcripts associated with acute cellular rejection (ACR); however, these lacked context critical to mechanistic understanding. We performed combined single cell transcriptomic and TCRα/β sequencing on rBx from patients ACR under differing immunosuppression (IS): tacrolimus, iscalimab, belatacept. TCR revealed a highly restricted CD8 + T clonal expansion (CD8 EXP ), independent HLA mismatch or IS type. Subcloning cDNAs into...
Background: Although parenteral sedation is often required in MRI studies children, it stressful and increases the cost of healthcare. Objectives: We evaluated impact music interventions children receiving for on total number doses medications, time, levels cortisol cytokines, success, adverse events, parental satisfaction, savings. Methods: conducted a prospective open unblinded four-arm clinical evaluation 471 1-12 years age undergoing sedation. Children were assigned to active therapy...
A critical appraisal and clinical application of Postma DF, van Werkhoven CH, Elden LJR, et al. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015;372(14):1312-1323. doi:10.1056/NEJMoa1406330