A5045227431- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Acute Lymphoblastic Leukemia research
- Chronic Myeloid Leukemia Treatments
- Cytokine Signaling Pathways and Interactions
- Quinazolinone synthesis and applications
- Protein Kinase Regulation and GTPase Signaling
- Multiple Myeloma Research and Treatments
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Retinoids in leukemia and cellular processes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer therapeutics and mechanisms
- Ubiquitin and proteasome pathways
- Lung Cancer Research Studies
- Melanoma and MAPK Pathways
- Histone Deacetylase Inhibitors Research
- Cell death mechanisms and regulation
- Chemokine receptors and signaling
- Lymphoma Diagnosis and Treatment
- Fungal Plant Pathogen Control
- Synthesis and biological activity
- PI3K/AKT/mTOR signaling in cancer
- Cell Image Analysis Techniques
- SARS-CoV-2 detection and testing
University of California, San Francisco
2013-2024
UCSF Benioff Children's Hospital
2013-2023
UCSF Helen Diller Family Comprehensive Cancer Center
2009-2017
City College of San Francisco
2010-2014
University of Michigan
2013
Medical College of Wisconsin
2013
City Of Hope National Medical Center
2013
Loyola University Medical Center
2013
National Cancer Institute
2013
City of Hope
2013
The p53 tumor suppressor limits proliferation in response to cellular stress through several mechanisms. Here, we test whether the recently described ability of limit stem cell self-renewal suppresses tumorigenesis acute myeloid leukemia (AML), an aggressive cancer which mutations are associated with drug resistance and adverse outcome. Our approach combined mosaic mouse models, Cre-lox technology, vivo RNAi disable simultaneously activate endogenous Kras G12D —a common AML lesion that...
Abstract Purpose: The clinical relevance of targeting the RAS/RAF/MEK/ERK pathway, activated in 70% to 80% patients with acute myelogenous leukemia (AML), is unknown. Experimental Design: Selumetinib an oral small-molecule inhibitor MAP–ERK kinase (MEK)-1/2. Forty-seven relapsed/refractory AML or 60 years old more untreated were enrolled on a phase II study. Patients stratified by FLT3 ITD mutation status. primary endpoint was response rate (complete, partial, and minor). Leukemia cells...
Abstract Acute lymphoblastic leukemia (ALL) is the most common cancer in children. The highest rates of treatment failure occur specific genetic subsets ALL, including hypodiploid B-cell ALL (B-ALL), for which effective alternative therapies to current intensive chemotherapy treatments have yet be developed. Here, we integrated biochemical and genomic profiling with functional drug assays select agents therapeutic potential against B-ALL. ABT-199, a selective Bcl-2 inhibitor, was reducing...
Diacylglycerol kinase alpha (DAGK alpha), like all type I DAGKs, has calcium regulatory motifs that act as negative regulators of enzyme activity and localization. Accordingly, DAGK is activated by phospholipase C-coupled receptors in a calcium-dependent manner. One the first functions attributed to lymphocytes was regulating interleukin 2-induced cell cycle entry. Interleukin-2 nonetheless exerts its action absence cytosolic increase. We have studied alternative receptor-derived signals...
Complementary tools are warranted to increase the sensitivity of initial testing for COVID-19. We identified a specific 'sandglass' aspect on white blood cell scattergram COVID-19 patients reflecting presence circulating plasmacytoid lymphocytes. Patients were dichotomized as COVID-19-positive or -negative based reverse transcriptase polymerase chain reaction (RT-PCR) and chest computed tomography (CT) scan results. Sensitivity specificity 85·9% 83·5% respectively. The positive predictive...
Abstract Stimulation via IL-2R ligation causes T lymphocytes to transit through the cell cycle. Previous experiments by our group have demonstrated that, in human cells, IL-2 binding induces phosphatidic acid production activation of α isoform diacylglycerol kinase. In this study, using IL-2-dependent mouse line CTLL-2, we demonstrate that pharmacological inhibition IL-2-induced kinase is found block late G1 S transition without affecting viability. Herein, has a profound effect on induction...
Protein kinase C (PKC) is the only PKC isoform recruited to immunological synapse after T cell receptor stimulation, suggesting that its activation mechanism differs from of other isoforms. Previous studies have suggested this selective recruitment may operate via a Vav-regulated, cytoskeletal-dependent mechanism, independent classical phospholipase C/diacylglycerol pathway. Here, we demonstrate that, together with tyrosine phosphorylation in regulatory domain, binding C-dependent...
The small GTPase Rac contributes to regulation of cytoskeletal rearrangement during chemokine-induced lymphocyte adhesion and migration in a multi-step process that is very precisely coordinated. Chimaerins are Rac1-specific GTPase-activating proteins unknown biological function, which have canonical diacylglycerol C1-binding domain. Here we demonstrate endogenous expression beta2-chimaerin T lymphocytes study the functional role this protein phorbol ester chemokine (CXCL12)-regulated T-cell...
Juvenile myelomonocytic leukemia is a rare myeloproliferative neoplasm characterized by hyperactive RAS signaling. Neurofibromin1 (encoded the NF1 gene) negative regulator of activation. Patients with neurofibromatosis type 1 harbor loss-of-function mutations in and have 200- to 500-fold increased risk juvenile leukemia. Leukemia cells from patients display hypersensitivity certain cytokines, such as granulocyte-macrophage colony-stimulating factor. The factor receptor utilizes...
Outcomes for pediatric relapsed or refractory acute lymphoblastic leukemia (ALL) remain unsatisfactory. Administration of Inotuzumab ozogamicin (InO), a CD22-targeted antibody-drug conjugate, has shown remarkable activity but predictors response to InO with improved accuracy over CD22 expression and site density have not been reported. We analyzed 68 samples from 28 patients enrolled in Children's Oncology Group trial AALL1621 (NCT02981628) collected before after treatment InO. utilized...
Hypodiploid acute lymphoblastic leukemia (ALL) is an aggressive blood cancer with a poor prognosis despite intensive chemotherapy or stem cell transplant. Children and adolescents positive end-of-induction minimal residual disease have overall survival lower than 30%. However, data regarding therapeutic alternatives for this nearly nonexistent, emphasizing the critical need new adjunctive therapies that can improve outcomes. We previously reported on efficacy of venetoclax (ABT-199) in...
Targeting signaling pathways upstream of oncogenic Ras may have therapeutic benefit in the treatment leukemia.
Somatic mutations that lead to constitutive activation of NRAS and KRAS proto-oncogenes are among the most common in human cancer frequently occur acute myeloid leukemia (AML). An inducible NRAS(V12)-driven AML mouse model has established a critical role for continued NRAS(V12) expression maintenance. In this genetic suppression results rapid remission, but some mice undergo spontaneous relapse with NRAS(V12)-independent (NRI) AMLs providing an opportunity identify mechanisms bypass...
6582 Background: RAS-RAF-MEK-ERK pathway is activated in >75% of AML patients (pts). Selumetinib (AZD6244) an orally bioavailable small molecule inhibitor the MEK kinase. We report here results a phase II multicenter trial using selumetinib advanced pts. Methods: Pts ≥18 years (yrs) with relapsed/refractory or ≥60 yrs old untreated who were not candidates for standard chemotherapy eligible. received 100mg twice daily. screened KRAS, NRAS and FLT3 mutations. Analysis p-ERK (downstream MEK)...