A5013236796- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Acute Lymphoblastic Leukemia research
- Metabolism, Diabetes, and Cancer
- Epigenetics and DNA Methylation
- Hematopoietic Stem Cell Transplantation
- Histone Deacetylase Inhibitors Research
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- Cell Adhesion Molecules Research
- Occupational and environmental lung diseases
- Protein Degradation and Inhibitors
- Pluripotent Stem Cells Research
- Prostate Cancer Treatment and Research
- Immunotherapy and Immune Responses
- Chronic Myeloid Leukemia Treatments
- Ion Transport and Channel Regulation
- CRISPR and Genetic Engineering
- Natural Antidiabetic Agents Studies
- Cancer Research and Treatments
- Bacteriophages and microbial interactions
- Phytochemicals and Antioxidant Activities
- Immune Cell Function and Interaction
- Genomics and Rare Diseases
- Childhood Cancer Survivors' Quality of Life
University of Delaware
2020-2024
Alfred I. duPont Hospital for Children
2013-2022
Center for Cancer and Blood Disorders
2021-2022
Nemours Children's Health System
2021-2022
Dupont Hospital
2015-2021
DuPont (United States)
2014-2021
Amrita Vishwa Vidyapeetham
2007-2011
Albert Einstein College of Medicine
2011
Mahatma Gandhi University
2009
University of California, Los Angeles
2003-2007
Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed at high levels in prostate cancer and tumor-associated neovasculature. In this study, we report that PSMA internalized via clathrin-dependent endocytic mechanism internalization of mediated by the five N-terminal amino acids (MWNLL) present its cytoplasmic tail. Deletion tail abolished internalization. Mutagenesis acid residues position 2, 3, or 4 to alanine did not affect PSMA, whereas mutation 1 5 strongly...
GLUT4, a 12 transmembrane protein, plays major role in insulin mediated glucose transport muscle and adipocytes. For transport, the GLUT4 protein needs to be translocated plasma membrane from intracellular pool it is possible that certain compounds may able enhance this process. In present work, we have shown gallic acid can increase translocation uptake activity an Akt-independent but wortmannin-sensitive manner. Further analysis suggested of atypical kinase Czeta/lambda uptake.
Translocations involving the NUP98 gene produce NUP98-fusion proteins and are associated with a poor prognosis in acute myeloid leukemia (AML). MLL1 is molecular dependency leukemia, therefore we investigated efficacy of therapeutic blockade menin-MLL1 interaction models. Using mouse cell lines driven by NUP98-HOXA9 NUP98-JARID1A fusion oncoproteins, demonstrate that NUP98-fusion-driven sensitive to inhibitor VTP50469, an IC50 similar what have previously reported for MLL-rearranged NPM1c...
The Na,K-ATPase, consisting of alpha- and beta-subunits, regulates intracellular ion homeostasis. Recent studies have demonstrated that Na,K-ATPase also epithelial cell tight junction structure functions. Consistent with an important role in the regulation structure, both enzyme activity subunit levels are altered carcinoma. Previously, we shown repletion beta1-subunit (Na,K-beta) highly motile Moloney sarcoma virus-transformed Madin-Darby canine kidney (MSV-MDCK) cells suppressed their...
Abstract GLUT4 is a 12 transmembrane (TM) protein belonging to the Class I facilitated glucose transporter family that transports into cells in an insulin regulated manner. plays key role maintenance of blood homeostasis and inhibition activity may lead resistance, hallmark type 2 diabetes. No crystal structure data available for any members family. Here, this paper, we have generated homology model based on experimental GLUTI, obtained from Glycerol 3-phosphate transporter. The identified...
Background The inverse relationship between GLUT4 and RBP4 expression is known to play a role in the pathogenesis of type 2 diabetes. Elevated levels were shown cause insulin resistance muscles liver. Identification STRA6 as cell surface receptor for provides further link this axis hence we analyzed SNPs these three genes association with diabetes South Indian population. Methodology/Principal Findings Selected total 2002 individuals belonging Dravidian ethnicity, India, by Tetra Primer ARMS...
Abstract In an effort to identify acute myeloid leukemia (AML)-restricted targets for therapeutic development in AML, we analyzed the transcriptomes of 2051 children and young adults with AML compared expression profile normal marrow specimens. This analysis identified a large cohort AML-restricted genes high but low no hematopoiesis. Mesothelin (MSLN), known target solid tumors, was shown be highly overexpressed 36% (range, 5-1077.6 transcripts per million [TPM]) virtually absent 0.1-10.7...
Background Glucose transporter 4 (GLUT4) is an insulin facilitated glucose that plays important role in maintaining blood homeostasis. GLUT4 sequestered into intracellular vesicles unstimulated cells and translocated to the plasma membrane by various stimuli. Understanding structural details of will provide insights mechanism transport its regulation. To date, a crystal structure for not available. However, earlier work from our laboratory proposed well validated homology model based on...
Chemicals and reagentsTissue culture media supplements were purchased from Sigma Aldrich (St Louis,
The bone marrow microenvironment plays an important role in acute lymphoblastic leukemia (ALL) cell proliferation, maintenance, and resistance to chemotherapy. Annexin II (ANX2) is abundantly expressed on cells complexes with p11 form ANX2/p11-hetero-tetramer (ANX2T). We present evidence that upregulated refractory ALL lines patient samples. A small molecule inhibitor disrupts ANX2/p11 interaction (ANX2T inhibitor), anti-ANX2 antibody, knockdown of p11, abrogated adhesion osteoblasts,...
Generation of orthotopic xenograft mouse models leukemia is important to understand the mechanisms leukemogenesis, cancer progression, its cross talk with bone marrow microenvironment, and for preclinical evaluation drugs. In these models, following intravenous injection, leukemic cells home proliferate there before infiltrating other organs, such as spleen, liver, central nervous system. Moreover, have been shown accurately recapitulate human disease correlate patient response therapy...
Abstract Relapse remains a major obstacle to achieving 100% overall survival rate in pediatric hematologic malignancies like acute lymphoblastic leukemia (ALL). often results from the development of chemoresistance. One mechanisms chemoresistance involves ALL cell interactions with bone marrow (BM) microenvironment, providing sanctuary. This phenomenon is known as BM microenvironment-induced chemoprotection. Members transmembrane 4 superfamily (tetraspanins; TSPANs) are mediate...
Acute myeloid leukemia (AML) in children remains deadly, despite the use of maximally intensive therapy. Because stem cells (LSCs) significantly contribute to chemoresistance and relapse, therapies that specifically target LSCs are likely be more beneficial improving outcome. known have high telomerase activity is negatively correlated with survival pediatric AML. We evaluated preclinical efficacy imetelstat, an oligonucleotide inhibitor patient-derived xenograft (PDX) lines Imetelstat...
Abstract Background Pediatric leukemias have a diverse genomic landscape associated with complex structural variants, including gene fusions, insertions and deletions, single nucleotide variants. Routine karyotype fluorescence in situ hybridization (FISH) techniques lack sensitivity for smaller alternations. Next-generation sequencing (NGS) assays are being increasingly utilized assessment of these various lesions. However, standard NGS lacks quantitative minimal residual disease (MRD)...
Children with Down syndrome (DS) have a high risk for acute myeloid leukemia (DS-ML). Genomic characterization of DS-ML blasts showed the presence unique mutations in GATA1, an essential hematopoietic transcription factor, leading to production truncated from GATA1 (GATA1s). GATA1s, together trisomy 21, is sufficient develop pre-leukemic condition called transient abnormal myelopoiesis (TAM). Approximately 30% these cases progress into by acquisition additional somatic stepwise manner. We...
Abstract Prostate-specific membrane antigen (PSMA) is an important biomarker expressed in prostate cancer cells with levels proportional to tumor grade. The association and correlation disease stage portend a promising role for PSMA as antigenic target antibody-based therapies. Successful application of such modalities necessitates detailed knowledge the subcellular localization trafficking antigen. In this study, we show that predominantly apical plasma epithelial gland well-differentiated...
Background GLUT4 is a predominant insulin regulated glucose transporter expressed in major disposal tissues such as adipocytes and muscles. Under the unstimulated state, resides within intracellular vesicles. Various stimuli translocate this protein to plasma membrane for transport. In absence of crystal structure GLUT4, very little known about mechanism transport by protein. Earlier we proposed homology model performed conventional molecular dynamics study revealing conformational...
Na(+)/Ca(2+) exchanger-1 (NCX1) is a major calcium extrusion mechanism in renal epithelial cells enabling the efflux of one Ca(2+) ion and influx three Na(+) ions. The gradient for this exchange activity provided by Na,K-ATPase, hetero-oligomer consisting catalytic α-subunit regulatory β-subunit (Na,K-β) that also functions as motility tumor suppressor. We showed earlier mice with heart-specific ablation (KO) Na,K-β had specific reduction NCX1 protein were ouabain-insensitive. Here, we...