A5034570760- PI3K/AKT/mTOR signaling in cancer
- Thyroid Cancer Diagnosis and Treatment
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- T-cell and Retrovirus Studies
- Metabolism, Diabetes, and Cancer
- Glutathione Transferases and Polymorphisms
- Ubiquitin and proteasome pathways
- Nutrition, Genetics, and Disease
- Cell death mechanisms and regulation
- Estrogen and related hormone effects
- Cancer, Lipids, and Metabolism
- Genetic factors in colorectal cancer
- Renal and related cancers
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Chromosomal and Genetic Variations
- Thyroid Disorders and Treatments
- Cancer-related gene regulation
- RNA modifications and cancer
- Polyamine Metabolism and Applications
- Chronic Myeloid Leukemia Treatments
- Protein Kinase Regulation and GTPase Signaling
- Microtubule and mitosis dynamics
Albert Einstein College of Medicine
2014-2024
Montefiore Medical Center
2020
AstraZeneca (United States)
2020
King Faisal Specialist Hospital & Research Centre
2019
Baylor College of Medicine
2019
National Institutes of Health
2019
The Bronx Defenders
2015
Memorial Sloan Kettering Cancer Center
1998-2014
Università Cattolica del Sacro Cuore
2011
Fox Chase Cancer Center
2004-2011
Complete inactivation of the PTEN tumor suppressor gene is extremely common in advanced cancer, including prostate cancer (CaP). However, one allele already lost vast majority CaPs at presentation. To determine consequence dose variations on progression, we have generated by homologous recombination a hypomorphic Pten mouse mutant series with decreasing activity: Ptenhy/+ > Pten+/− Ptenhy/− (mutants which rescued embryonic lethality due to complete inactivation) conditional knockout (Ptenpc)...
In many species, the Sox2 transcription factor is a marker of nervous system from beginning its development, and we have previously shown that expressed in embryonic neural stem cells. It also in, essential for, totipotent inner cell mass cells other multipotent lineages, ablation causes early lethality. To investigate role system, generated different mouse mutant alleles: null allele(Sox2β-geo `knock-in'), regulatory allele (Sox2ΔENH), which cell-specific enhancer deleted. precursors...
Inactivating mutations in the PTEN tumor suppressor gene, encoding a phosphatase, occur three related human autosomal dominant disorders characterized by susceptibility. Here it is shown that Pten heterozygous ( +/− ) mutants develop lethal polyclonal autoimmune disorder with features reminiscent of those observed Fas-deficient mutants. Fas-mediated apoptosis was impaired mice, and T lymphocytes from these mice show reduced activation-induced cell death increased proliferation upon...
Activation of Akt, or protein kinase B, is frequently observed in human cancers. Here we report that Akt activation via overexpression a constitutively active form the loss PTEN can overcome G(2)/M cell cycle checkpoint induced by DNA damage. Activated also alleviates reduction CDC2 activity and mitotic index upon exposure to In addition, found null embryonic stem (ES) cells transit faster from G(1) phase when compared wild-type ES inhibition phosphoinositol-3-kinase (PI3K) HEK293 elicits...
The tumor suppressor PTEN is frequently inactivated in human cancers. A major downstream effector of Akt, which hyperactivated via inactivation. It not known, however, whether diminished Akt activity sufficient to inhibit tumorigenesis initiated by Pten deficiency. Here we showed that the deficiency Akt1 dramatically development +/− mice. had a profound effect on endometrium and prostate neoplasia, two types cancer, mutated, also affected thyroid adrenal medulla tumors intestinal polyps....
Thyroid tumors arising from the follicular cells often harbor mutations leading to constitutive activation of PI3K and Ras signaling cascades. However, it is still unclear what their respective contribution neoplastic process is, as well extent they interact. We have used mice harboring a Kras oncogenic mutation Pten deletion targeted thyroid epithelium address in vivo these questions. Here, we show that although each two pathways, alone, unable transform cells, simultaneous highly...
Abstract Inactivation and silencing of the tumor suppressor PTEN are found in many different epithelial tumors, including thyroid neoplasia. Cowden Disease patients, who harbor germ-line mutations, often display abnormalities, multinodular goiter follicular adenomas, at increased risk cancer. To gain insights into role plays function disease, we have generated a mouse strain, which Cre-mediated recombination is used to specifically delete Pten thyrocytes. We that mutant mice develop diffuse...
Chronic myelogenous leukemia (CML) is a disease characterized by the presence of p210<sup>bcr-abl</sup>, chimeric protein with tyrosine kinase activity. Substrates for p210<sup>bcr-abl</sup> are likely to be involved in pathogenesis CML. Here we describe purification, cDNA cloning, and characterization 56-kDa phosphorylated protein, p56<sup>dok-2</sup> (Dok-2), from expressing cells. The human <i>dok-2</i> encodes 412-amino acid predicted N-terminal pleckstrin homology domain as well several...
We generated purine nucleoside phosphorylase (PNP)-deficient mice to gain insight into the mechanism of immune deficiency disease associated with PNP in humans. Similar human disease, causes an immunodeficiency that affects T lymphocytes more severely than B lymphocytes. knockout exhibit impaired thymocyte differentiation, reduced mitogenic and allogeneic responses, decreased numbers maturing thymocytes peripheral cells. PNP-deficient increased apoptosis vivo higher sensitivity gamma...
p62dok has been identified as a substrate of many oncogenic tyrosine kinases such the chronic myelogenous leukemia (CML) chimeric p210bcr-abl oncoprotein. It is also phosphorylated upon activation receptors and cytoplamic kinases. However, biological functions in normal cell signaling well leukemogenesis are yet not fully understood. Here we show, hemopoietic nonhemopoietic cells derived from p62dok−/− mice, that loss results increased proliferation growth factor treatment. Moreover, Ras...
Abstract PTEN is a tumor suppressor gene frequently mutated in human cancers. In vitro and vivo studies have shown that can exert its suppressive function through variety of mechanisms, including regulation cell death proliferation. However, it still unclear which the many downstream pathways are critical each different tissue, vivo. Loss earliest detectable genetic lesion estrogen-related type I (endometrioid) endometrial cancer. Pten+/− mice develop neoplastic lesions with full penetrance,...
A novel endogenous retroviral sequence (ERV-9) has been isolated from a human embryonal carcinoma cDNA library by hybridization to probe containing recently described repetitive element. DNA analysis of the 4kb insert (pHE.1) revealed presence ORFs potentially coding for putative retrovirus-related gag, pol and env proteins. Northern blot RNase protection experiments showed that RNA homologous pHE.1 is detected only in cells as 8 kb mRNA, its expression negatively regulated during retinoic...