Sameet Mehta

Sameet Mehta
SEMA4 · Precision Oncology

Ph.D.

About

75
Publications
7,530
Reads
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1,631
Citations
Citations since 2017
46 Research Items
1131 Citations
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2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
Introduction
Sameet Mehta currently works at the Yale Center for Genome Analysis, Yale University. Sameet does research in Bioinformatics, Systems Biology and Cell Biology.
Additional affiliations
November 2014 - present
Yale University
Position
  • Research Associate
May 2010 - October 2014
National Cancer Institute (USA)
Position
  • Visiting Fellow
Description
  • High throughput data management and analysis.
May 2010 - October 2014
National Cancer Institute (USA)
Position
  • Visiting Fellow
Education
December 2002 - August 2009
Independent Researcher
Independent Researcher
Field of study
  • Zoology
June 1999 - June 2001

Publications

Publications (75)
Article
Full-text available
Genetic variants in the third intron of the PRDM6 gene have been associated with blood pressure traits in multiple genome-wide association studies (GWAS). By combining fine mapping, massive-ly parallel reporter assays, and gene editing we identified the causal variants for hypertension as super-enhancers that drive the expression of PRDM6 and are p...
Article
Full-text available
Background: Neuronopathic Gaucher disease (nGD) is a rare neurodegenerative disorder caused by biallelic mutations in GBA and buildup of glycosphingolipids in lysosomes. Neuronal injury and cell death are prominent pathological features; however, the role of GBA in individual cell types and involvement of microglia, blood-derived macrophages, and i...
Preprint
Full-text available
Background Neuronopathic Gaucher Disease (nGD) is a rare neurodegenerative disorder caused by biallelic mutations in Gba , and buildup of glycosphingolipids in lysosomes. Neuronal injury and cell death are prominent pathological features, however the role of Gba in individual cell types and involvement of microglia, blood derived macrophages and im...
Article
Full-text available
The molecular mechanisms that drive the acquisition of distinct neural crest cell (NCC) fates is still poorly understood. Here, we identify Prdm6 as an epigenetic modifier that temporally and spatially regulates the expression of NCC specifiers and determines the fate of a subset of migrating Cardiac NCCs (CNCCs). Using transcriptomic analysis, gen...
Article
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Adiponectin-mediated pathways contribute to mammalian homeostasis; however, little is known about adiponectin and adiponectin receptor signaling in arthropods. In this study, we demonstrate that Ixodes scapularis ticks have an adiponectin receptor-like protein (ISARL) but lack adiponectin - suggesting activation by alternative pathways. ISARL expre...
Preprint
Full-text available
Adiponectin-mediated pathways contribute to mammalian homeostasis; however, little is known about adiponectin and adiponectin receptor signaling in arthropods. In this study, we demonstrate that Ixodes scapularis ticks have an adiponectin receptor-like protein (ISARL) but lack adiponectin – suggesting activation by alternative pathways. ISARL expre...
Article
Hypertension induces significant aortic remodelling, often adaptive but sometimes not. To identify immuno-mechanical mechanisms responsible for differential remodelling, we studied thoracic aortas from 129S6/SvEvTac and C57BL/6 J mice before and after continuous 14-day angiotensin II infusion, which elevated blood pressure similarly in both strains...
Article
Full-text available
Research Question: Can cumulus cells be employed as a non-invasive target for the study of determinants of preimplantation embryo quality? Design Cumulus cells were collected from Monosomy 21, Trisomy 21 and Euploid embryos and subjected to RNA sequencing analysis and Real Time PCR assays. The differential gene expression was analyzed for differen...
Article
Full-text available
Gonadotoxic chemotherapeutics, such as cyclophosphamide, can cause early menopause and infertility in women. Earlier histological studies showed ovarian reserve depletion via severe DNA damage and apoptosis, but others suggested activation of PI3K/PTEN/Akt pathway and follicle ‘burn-out’ as a cause. Using a human ovarian xenograft model, we perform...
Article
Gonadotoxic chemotherapeutics, such as cyclophosphamide, can cause early menopause and infertility in women. Earlier histological studies showed ovarian reserve depletion via severe DNA damage and apoptosis, but others suggested activation of PI3K/PTEN/Akt pathway and follicle 'burn-out' as a cause. Using a human ovarian xenograft model, we perform...
Poster
Background: Many genetic mutations affect aortic structure and function in mice, but little is known about the influence of background strain. We compared the biomechanical, structural, and gene expression responses of C57BL/6J and 129SvEv aortas to angiotensin II (AngII)-induced hypertension. Methods: After AngII infusion (14-day, 1000 ng/kg/min)...
Article
Full-text available
OBJECTIVE: To determine if the transcriptomic profile of cumulus cells (CCs) from oocytes that resulted in embryos diagnosed to be whole chromosome aneuploid for chromosome 21 by preimplantation genetic testing for aneuploidy (PGT-A) differs from that of CCs of oocytes that resulted in euploid embryos. DESIGN: Prospective experimental study. MATERI...
Article
Full-text available
Ticks deposit salivary proteins into the skin during a bite to mediate acquisition of a blood meal. Acquired resistance to tick bites has been demonstrated to prevent Borrelia burgdorferi sensu lato (s.l.) transmission. However, the mechanism of resistance, as well as the protective antigens, have remained elusive. To address these unknowns, we uti...
Article
The largest risk factor for skin cancers such as melanoma is past sun exposure, so an objective measurement of traces of an individual’s sun history would allow a general practitioner to identify people who should be monitored for early cancer detection. If the genome contains outlier DNA sequences hypersensitive to environmental agents such as ult...
Preprint
Full-text available
Gonadotoxic chemotherapeutics, such as cyclophosphamide, cause early menopause and infertility in women. Earlier histological studies showed ovarian reserve depletion via severe DNA damage and apoptosis, but others suggested activation of PI3K/PTEN/Akt pathway and follicle ‘burn-out’ as a cause. Using a human ovarian xenograft model, we performed s...
Preprint
One of the first events in the development of the cardiovascular system is morphogenesis of the main embryonic artery, the dorsal aorta (DA). The DA forms via a conserved genetic process mediated by the migration, specification, and organization of endothelial progenitor cells into a distinct arterial lineage and vessel type. Several angiogenic fac...
Article
Understanding HIV-1–host interactions can identify the cellular environment supporting HIV-1 reactivation and mechanisms of clonal expansion. We developed HIV-1 SortSeq to isolate rare HIV-1–infected cells from virally suppressed, HIV-1–infected individuals upon early latency reversal. Single-cell transcriptome analysis of HIV-1 SortSeq ⁺ cells rev...
Article
Regulatory T cells are not terminally differentiated but can acquire effector properties. Here we report Human Endogenous Retrovirus 1 (HERV1-env) induction of endoplasmic reticulum (ER) stress with Unfolded Protein Response (UPR) activation, through its interaction with ATF6. UPR activation cleaves ATF6 to its α and β isoforms. ATF6α up-regulates...
Article
Full-text available
Vascular inflammation is present in many cardiovascular diseases, and exogenous glucocorticoids have traditionally been used as a therapy to suppress inflammation. However, recent data have shown that endogenous glucocorticoids, acting through the endothelial glucocorticoid receptor, act as negative regulators of inflammation. Here, we performed Ch...
Article
Full-text available
Smooth muscle cell (SMC) proliferation has been thought to limit the progression of thoracic aortic aneurysm and dissection (TAAD) because loss of medial cells associates with advanced disease. We investigated effects of SMC proliferation in the aortic media by conditional disruption of Tsc1, which hyperactivates mTOR complex 1. Consequent SMC hype...
Article
Full-text available
If the genome contains outlier sequences extraordinarily sensitive to environmental agents, these would be sentinels for monitoring personal carcinogen exposure and might drive direct changes in cell physiology rather than acting through rare mutations. New methods, adductSeq and freqSeq, provided statistical resolution to quantify rare lesions at...
Article
Full-text available
microRNA-21 (miR-21) is the most commonly upregulated miRNA in solid tumors. This cancer-associated microRNA (oncomiR) regulates various downstream effectors associated with tumor pathogenesis during all stages of carcinogenesis. In this study, we analyzed the function of miR-21 in noncancer cells of the tumor microenvironment to further evaluate i...
Article
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γ-aminobutyric acid (GABA) inhibitory interneurons play a key role in efferent and afferent control of principle neuron activity in the prefrontal cortex (PFC), thereby regulating signal integrity of cognitive and behavioral processes. Recent evidence suggests that specific subtypes of interneurons in the PFC mediate stress-induced depressive-like...
Article
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In fungi, ergosterol is an essential component of the plasma membrane. Its biosynthesis from acetyl-CoA is the primary target of the most commonly used antifungal drugs. Here, we show that the pantothenate kinase Cab1p, which catalyzes the first step in the metabolism of pantothenic acid for CoA biosynthesis in budding yeast (Saccharomyces cerevisi...
Article
Genomic analyses of patients with congenital heart disease (CHD) have identified significant contribution from mutations affecting cilia genes and chromatin remodeling genes; however, the mechanism(s) connecting chromatin remodeling to CHD is unknown. Histone H2B monoubiquitination (H2Bub1) is catalyzed by the RNF20 complex consisting of RNF20, RNF...
Article
Full-text available
HIV +Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4 +T cells with resistance specific to R5-tropic HIV, reversed after introduction of ccr5. R5 resistance was not observed in macrophages and depended upon the method of T cell act...
Article
Central nervous system (CNS) immune activation is an important driver of neuronal injury during several neurodegenerative and neuroinflammatory diseases. During HIV infection, CNS immune activation is associated with high rates of neurocognitive impairment, even during sustained long-term suppressive antiretroviral therapy (ART). However, the cellu...
Article
As somatic cells are converted into induced pluripotent stem cells (iPSCs), their chromatin is remodeled to a pluripotent configuration with unique euchromatin-to-heterochromatin ratios, DNA methylation patterns, and enhancer and promoter status. The molecular machinery underlying this process is largely unknown. Here, we show that embryonic stem c...
Article
Full-text available
De novo autoimmune hepatitis (DAIH) is an important cause of late allograft dysfunction following liver transplantation, but its cause and underlying pathogenesis remains unclear. We sought to identify specific innate and adaptive immune mechanisms driving the pro-inflammatory cytokine secreting regulatory T cell (Treg) phenotype in DAIH and determ...
Preprint
Full-text available
Central nervous system (CNS) immune activation in an important driver of neuronal injury during several neurodegenerative and neuroinflammatory diseases. During HIV infection, CNS immune activation is associated with high rates of neurocognitive impairment, even with sustained long-term suppressive antiretroviral therapy (ART). However, the cellula...
Article
Full-text available
Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of Leptospira. In our comprehensive genomic analysis of 20 Leptospira spp. we identified seven pathogen specific Two-Component System (TCS) proteins. Disruption of tw...
Article
Full-text available
Key Points Altered number, subset composition, and function of bone marrow innate lymphoid cells are early events in monoclonal gammopathies. Pomalidomide therapy leads to reduction in Ikzf1 and Ikzf3 and enhanced human innate lymphoid cell function in vivo.
Article
Post-translational protein modification by the small ubiquitin-related modifier (SUMO) regulates numerous cellular pathways, including transcription, cell division, and genome maintenance. The SUMO protease Ulp2 modulates many of these SUMO-dependent processes in budding yeast. From whole-genome RNA sequencing (RNA-seq), we unexpectedly discovered...
Article
Full-text available
Eukaryotic genomes are folded into three-dimensional structures, such as self-associating topological domains, the borders of which are enriched in cohesin and CCCTC-binding factor (CTCF) required for long-range interactions. How local chromatin interactions govern higher-order folding of chromatin fibres and the function of cohesin in this process...
Article
Full-text available
The regulation of protein-coding and noncoding RNAs is linked to nuclear processes, including chromatin modifications and gene silencing. However, the mechanisms that distinguish RNAs and mediate their functions are poorly understood. We describe a nuclear RNA-processing network in fission yeast with a core module comprising the Mtr4-like protein,...
Article
Full-text available
Eukaryotic genomes are folded into three-dimensional structures, such as self-associating topological domains, the borders of which are enriched in cohesin and CCCTC-binding factor (CTCF) required for long-range interactions. How local chromatin interactions govern higher-order folding of chromatin fibres and the function of cohesin in this process...
Article
Full-text available
Heterochromatin causes epigenetic repression that can be transmitted through multiple cell divisions. However, the mechanisms underlying silencing and stability of heterochromatin are not fully understood. We show that heterochromatin differs from euchromatin in histone turnover and identify histone deacetylase (HDAC) Clr3 as a factor required for...
Article
Full-text available
RNA interference (RNAi) is a conserved mechanism in which small interfering RNAs (siRNAs) guide the degradation of cognate RNAs, but also promote heterochromatin assembly at repetitive DNA elements such as centromeric repeats. However, the full extent of RNAi functions and its endogenous targets have not been explored. Here we show that, in the fis...
Article
Full-text available
Schizosaccharomyces pombe cells switch mating type by replacing genetic information at the expressed mat1 locus with sequences copied from mat2-P or mat3-M silent donor loci. The choice of donor locus is dictated by cell type, such that mat2 is the preferred donor in M cells and mat3 is the preferred donor in P cells. Donor choice involves a recomb...
Article
Full-text available
Genes coding for drought response element binding (DREB) proteins regulate transcription of a large number of downstream genes involved in the plant response to abiotic stresses. However the regulation of DREB genes themselves is not well understood. Using a bioinformatics approach, we identified the over-represented motifs in promoters of DREB gen...
Data
Qualitative analysis of proteins used for in vitro pulldowns. Coomassie stained gels depicting the purity of various GST-β-catenin (lanes 3–5, 9, 10) and SATB1 (lanes 13, 14) truncations used in GST pulldown experiments. His-SATB1 corresponds to 6× histidine-tagged full-length SATB1, CD+HD is the C-terminal half of SATB1 containing the DNA-binding...
Data
Common targets of SATB1 and β-catenin. Expression profiling of cells in which β-catenin was overexpressed, knocked out, or mutated available on NCBI public domain GEO datasets GSE1473 [60] and GSE1579 [61] were analyzed against expression profiling of SATB1 overexpression series GSE4317 [21] as described below. Analysis of multiple arrays generated...
Data
SATB1 and β-catenin interact in vivo. (A) Coimmunoprecipitation reactions was performed by separately incubating anti-β-catenin and anti-SATB1 antibodies with aliquots of Jurkat nuclear extract as described in Materials and Methods followed by Western blot (WB) using anti-SATB1 and anti-β-catenin, respectively. IgH, immunoglobulin heavy chain. (B)...
Data
β-catenin activates SATB1-mediated transcription. The functional consequence of overexpression of SATB1 and constitutively active mutant β-catenin (T41A) on MAR-linked reporter assay was monitored as described in Materials and Methods. The IgH-MAR-luciferase construct consists of seven copies of the 25 bp AT-rich core of the IgH-MAR [62] that is a...
Data
Analysis of SBSs in regulatory regions of multiple genes. EMSA analysis was performed using 32P-labeled upstream regulatory regions from CHUK, PPM1A, c-Myc genes, and the major breakpoint region of BCL2. Purified GST was used as a control for the GST:SATB1 fusion protein. The multiple regions tested from the 1 kb upstream region of CHUK and PPM1A a...
Data
SATB1 and β-catenin occupy the SBSs in IL-2 and c-Myc promoters in vivo. (A) ChIP-PCR analysis in Jurkat cells showing the binding of SATB1 and β-catenin on IL-2 promoter in presence (+) and absence (−) of LiCl. ChIP analysis was performed as described in Materials and Methods. LiCl treatment resulted in increased occupancy of SATB1 at IL-2 promote...
Data
Confirmation of polarization of CD4+ T cells to TH1 and TH2 subsets. Quantitation of marker cytokines in culture supernatants harvested from TH cells grown for 72 h was performed simultaneously using a multiplex bead array reader as described in Materials and Methods. As expected, TH1 cells produced IFN-γ and IL-12 whereas TH2 cells produced IL-4,...
Data
SATB1 does not bind to the TCF consensus in vitro. In vitro binding analysis of TCF consensus binding site using recombinant SATB1 was performed by EMSA as described in Materials and Methods. The various panels depict EMSA using 32P-labeled wild-type (lanes 1–5) and mutant TCF (lanes 6–10) consensus sequences. 32P-labeled IgH-MAR was used as a posi...
Data
Analysis of c-Maf expression in differentiating TH cells. Naïve CD4+ T cells were transfected with duplex siSATB1, siβ-catenin, or SATB1 overexpression plasmid DNA and differentiated ex vivo as described in Materials and Methods. As the control, duplex scrambled RNA (Scr) was transfected. Upon polarization for 72 h, total RNA was isolated and GATA-...
Data
Analysis of upstream regulatory regions of GATA-3. In vitro binding analysis of GATA-3 promoter using recombinant SATB1 was performed by EMSA as described in Materials and Methods. The binding of SATB1 across the 2 kb (+1 to −2,000 bp) upstream regulatory region of GATA-3 was monitored by using 32P-labeled fragments of this region. We focused on a...
Data
List of genes and gene IDs. The genes studied here or mentioned in the text are tabulated along with their respective gene IDs. (0.05 MB DOC)
Data
SATB1 and β-catenin colocalize in the nuclei of mouse thymocytes. Triple stained immunofluorescence image (Alexa 488, Alexa 546, and DAPI). Thymocyte nuclei were counterstained with DAPI to mark the DAPI intense and less intense areas in the nuclei. The movie depicts a 3-D stack of images from top to bottom in the same thymocytes as in Figure 1A. T...
Data
Human thymocytes were isolated from neonatal thymii as described in Materials and Methods and co-cultured with the OP9 or OP9-DL1 cells as described [63]. In brief, thymocytes were cultured on monolayers of OP9 or OP9-DL1 cells for 48 h in RPMI 1640 medium (Invitrogen) supplemented with 10% FCS, along with Wnt3a (10 µg/ml) (Wnt agonist) or DKK1 (10...
Data
IL-4 is downregulated upon siRNA-mediated silencing of SATB1 in differentiating TH2 cells. Human CD4+ T cells were transfected with Scrambled (Scr) and si SATB1 synthetic duplex RNAs and then polarized to TH2 as described in Materials and Methods. After 72 h the cells were harvested and used for monitoring the expression of IL-4. (A) IL-4 gene expr...
Data
β-catenin forms a characteristic “cage-like” substructure in the nuclei of mouse thymocytes. Single stained immunofluorescence image (Alexa 488). The movie depicts a 3-D stack of images from top to bottom in the same thymocytes as in Figure 1A. Images were captured using the Apotome module (Carl Zeiss) as described above. β-catenin staining pattern...
Article
Full-text available
In vertebrates, the conserved Wnt signalling cascade promotes the stabilization and nuclear accumulation of beta-catenin, which then associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs) to activate target genes. Wnt/beta -catenin signalling is essential for T cell development and differentiation. Here we show that special...