A5072733057- Ubiquitin and proteasome pathways
- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Hematopoietic Stem Cell Transplantation
- Lymphoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Multiple Myeloma Research and Treatments
- Mesenchymal stem cell research
- Pluripotent Stem Cells Research
- Chronic Lymphocytic Leukemia Research
- RNA modifications and cancer
- Pancreatic function and diabetes
- Glycosylation and Glycoproteins Research
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Animal Genetics and Reproduction
- Lung Cancer Research Studies
- Immune Response and Inflammation
- Chemokine receptors and signaling
- Cancer-related gene regulation
- TGF-β signaling in diseases
University of Utah
2023-2024
Huntsman Cancer Institute
2023-2024
University of Nebraska Medical Center
2015-2022
Susan Thompson Buffett Foundation
2020
Fred and Pamela Buffett Cancer Center
2020
New York University
2011-2016
University School
2011-2015
Howard Hughes Medical Institute
2010-2013
KU Leuven
2010-2013
University of Minnesota
2002-2010
Conditional knockout mice and transgenic expressing recombinases, reporters, inducible transcriptional activators are key for many genetic studies comprise over 90% of mouse models created. generated using labor-intensive methods homologous recombination in embryonic stem cells available only ~25% all genes. Transgenic by random genomic insertion approaches pose problems unreliable expression, thus there is a need targeted-insertion models. Although CRISPR-based strategies were reported to...
B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common B-NHL, such as diffuse large lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, mantle cell remain less extensively characterized. Furthermore, B-NHL thus far not compared using same methodology to identify conserved or subtype-specific patterns alterations. Here, we employed a targeted...
Little is known on post-transcriptional regulation of adult and embryonic stem cell maintenance differentiation. Here we characterize the role Ddb1, a component CUL4-DDB1 ubiquitin ligase complex. Ddb1 highly expressed in multipotent hematopoietic progenitors its deletion leads to abrogation both fetal hematopoiesis, targeting specifically transiently amplifying progenitor subsets. However, non-dividing lymphocytes has no discernible phenotypes. silencing activates Trp53 pathway significant...
Widespread use of liver transplantation in the treatment hepatic diseases is restricted by limited availability donated organs. One potential solution to this problem would be isolation and propagation progenitor cells or stem cells. Here, we report on a novel cell population from unmanipulated (that is, no prior exposure chemicals injury) adult rat liver. Rat were cultured following protocol developed our laboratory generate unique called liver-derived (LDPCs). LDPCs analyzed...
Abstract Acute myeloid leukemia (AML) is a devastating cancer affecting the hematopoietic system. Previous research has relied on RNA sequencing and microarray techniques to study downstream effects of genomic alterations. While these studies have proven efficacious, they fail capture changes that occur at proteomic level. To interrogate effect protein expression alterations in AML, we performed quantitative mass spectrometry parallel with RNAseq analysis using AML mouse models. These...
The hematopoietic system is maintained throughout life by stem cells that are capable of differentiating into all lineages. An intimate balance between self-renewal, differentiation, and quiescence required to maintain hematopoiesis disruption this can result in malignant transformation. FBXO9, the substrate recognition component from SCF E3 ubiquitin ligase family, downregulated patients with acute myeloid leukemia (AML) compared healthy bone marrow, downregulation particularly evident...
Abstract Embryonic stem cells (ESCs) and induced pluripotent (iPSCs) have unique characteristics where they can both contribute to all three germ layers in vivo self-renewal indefinitely vitro. Post-translational modifications of proteins, particularly by the ubiquitin proteasome system (UPS), control cell pluripotency, self-renewal, differentiation. A significant number UPS members (mainly ligases) regulate pluripotency influence ESC differentiation with key elements network (including...
Primitive human hematopoietic cells in granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood (MPB) are more difficult to transduce compared from umbilical cord blood. Based on the hypothesis that MPB may require different stimulation for efficient retroviral infection, we several culture conditions known induce cycling of primitive cells. MPB-derived CD34+ were stimulated presence or absence murine fetal liver cell line AFT024 trans-wells with G-CSF, stem (SCF), and...
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by clonal expansion of blasts in the bone marrow (BM). Despite advances therapy, prognosis for AML patients remains poor, and there need to identify novel molecular pathways regulating tumor cell survival proliferation. F-box ubiquitin E3 ligase, FBXO21, has low expression AML, but correlates with higher have poorer outcomes. Silencing FBXO21 human-derived lines primary patient samples leads differentiation, inhibition...
ABSTRACT The hematopoietic system is maintained throughout life by stem cells that are capable of differentiating into all lineages. An intimate balance between self-renewal, differentiation, and quiescence required to maintain hematopoiesis. Disruption this can result in malignancy, including acute myeloid leukemia (AML). FBXO9, from the F-box E3 ubiquitin ligases, down-regulated patients with AML compared normal bone marrow. FBXO9 substrate recognition component Skp1-Cullin-F-box...
ABSTRACT B-cell non-Hodgkin’s lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common B-NHL such as diffuse large (DLBCL) have been comprehensively interrogated at the genomic level. But rarer mantle cell (MCL) remain sparsely characterized. Furthermore, thus far not compared using same methodology to identify conserved or subtype-specific patterns alterations. Here, we employed a targeted hybrid-capture...
ABSTRACT RNA polymerase II subunit A Carboxy-Terminal Domain Phosphatase 1 (CTDP1), a member of the haloacid dehalogenase superfamily phosphatases, has defined role in transcriptional regulation, but emerging evidence suggests an expanded functional repertoire cell cycle and DNA damage response. In humans, splice site mutation CTDP1 gives rise to rare Congenital Cataracts Facial Dysmorphism Neuropathy syndrome, recent from our lab indicates is required for breast cancer growth proliferation....
ABSTRACT PI3K inhibitors that target the catalytic sub-unit p110 are used in cancer therapy to inhibit overactive signaling pathway. However, their clinical use is limited by severe adverse effects and development of resistance, highlighting need for further research on regulation We have identified FBXO21 ubiquitinates regulatory subunit p85α, silencing inhibits canonical signaling. To FBXO21, we developed a small molecule designed interfere with substrate:ligase interaction. Our novel...