- Epigenetics and DNA Methylation
- Colorectal Cancer Treatments and Studies
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- Histone Deacetylase Inhibitors Research
- Microtubule and mitosis dynamics
- Gastric Cancer Management and Outcomes
- Cancer Diagnosis and Treatment
- Biochemical and Molecular Research
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- DNA Repair Mechanisms
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Ferroptosis and cancer prognosis
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- PARP inhibition in cancer therapy
Saveetha University
2025
Indiana University School of Medicine
2017-2023
Indiana University
2023
Indiana University Bloomington
2017-2022
Abstract Despite the connection of secretory cells, including goblet and enteroendocrine (EEC) to distinct mucus-containing colorectal cancer histologic subtypes, their role in progression has been underexplored. Here, our analysis The Cancer Genome Atlas (TCGA) single-cell RNA-sequencing data demonstrates that EEC progenitor cells are enriched BRAF-mutant patient tumors, cell lines, patient-derived organoids. In cancer, progenitors were blocked from differentiating further by DNA...
Colorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced inflammation, mutagens, and/or microbiota. cancers activating mutations in BRAF associated distinct clinical characteristics, although the pathogenesis not well understood. The Wnt-driven multiple intestinal neoplasia (MinApcΔ716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model characterized IL17-dependent, distal colon adenomas. Herein, we...
Abstract Background Platinum based agents—cisplatin and carboplatin in combination with taxanes are used for the treatment of ovarian cancer (OC) patients. However, majority OC patients develop recurrent, platinum resistant disease that is uniformly fatal. enriches chemoresistant aldehyde dehydrogenase (ALDH) + stem cells (OCSCs), which contribute to tumor recurrence relapse. Acquired resistance also includes metabolic reprograming switching oxidative phosphorylation (OXPHOS). Chemosensitive...
Abstract Aberrant silencing of genes by DNA methylation contributes to cancer, yet how this process is initiated remains unclear. Using a murine model inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment epigenetic proteins chromatin, initiating and gene in tumors. Compared with normal epithelium noninflammation-induced tumors, tumors gained at CpG islands, some which are associated putative tumor suppressor genes. Hypermethylated exhibited...
Activation of the epithelial-to-mesenchymal transition (EMT) program is a critical mechanism for initiating cancer progression and migration. Colorectal cancers contain many genetic epigenetic alterations that can contribute to EMT. Mutations activating PI3K/AKT signaling pathway are observed in >40% patients with colorectal contributing increased invasion metastasis. Little known about how oncogenic pathways such as synergize chromatin modifiers activate EMT program. Lysine-specific...
Ovarian cancer is a deadly disease attributed to late-stage detection as well recurrence and the development of chemoresistance. stem cells (OCSCs) are hypothesized be largely responsible for emergence chemoresistant tumors. Although chemotherapy may initially succeed at decreasing size number tumors, it leaves behind residual malignant OCSCs. In this study, we demonstrate that aldehyde dehydrogenase 1A1 (ALDH1A1) essential survival We identified first-in-class ALDH1A1 inhibitor, compound
Tuberculosis (TB) remains a significant public health issue globally, with extra pulmonary tuberculosis (epTB) accounting for considerable number of TB cases. This study aims to improve our understanding epTB epidemiology by evaluating treatment outcomes and identifying factors associated positive negative results in patients. A retrospective was conducted from January 1, 2016, December 31, 2019. EpTB rifampicin-resistant were identified using the GeneXpert MTB/RIF assay. Logistic regression...
Ovarian cancer (OC) is a lethal gynecological malignancy with five-year survival rate of only 46%. Development resistance to platinum-based chemotherapy common cause high mortality rates among OC patients. Tumor and transcriptomic heterogeneity are drivers platinum in OC. Platinum-based enriches for ovarian stem cells (OCSCs) that chemoresistant contribute disease recurrence relapse. Studies examining the effect different treatments on subpopulations HGSOC cell lines limited. Having...
Platinum resistance is a common occurrence in high-grade serous ovarian cancer and major cause of deaths. agents form DNA cross-links, which activate nucleotide excision repair (NER), Fanconi anemia, homologous recombination (HRR) pathways. Chromatin modifications occur the vicinity damage play an integral role response (DDR). modifiers, including polycomb repressive complex 1 (PRC1) members, chromatin structure are frequently dysregulated can potentially contribute to platinum resistance....
Ovarian cancer is a deadly disease attributed to late-stage detection as well recurrence and development of chemoresistance. stem cells (OCSCs) are hypothesized be largely responsible for emergence chemoresistant tumors. Although chemotherapy may initially succeed at decreasing the size number tumors, it leaves behind residual malignant OCSCs. In this study, we demonstrate that Aldehyde dehydrogenase 1A1 (ALDH1A1) essential survival We identified novel ALDH1A1 inhibitor, compound 974, used...
Abstract Despite the connection to distinct mucus-containing colorectal cancer (CRC) histological subtypes, role of secretory cells, including goblet and enteroendocrine (EEC) in CRC progression has been underexplored. Analysis TCGA single cell RNA sequencing data demonstrates that multiple progenitor populations are enriched BRAF- mutant patient tumors lines. Enrichment EEC progenitors BRAF -mutant is maintained by DNA methylation silencing NEUROD1 , a key gene required for differentiation...
Abstract Ovarian cancer is a deadly disease attributed to late-stage detection as well recurrence and development of chemoresistance. stem cells (OCSCs) are hypothesized be largely responsible for emergence chemoresistant tumors. Although chemotherapy may initially succeed at decreasing the size number tumors, it leaves behind residual malignant OCSCs. In this study, we demonstrate that Aldehyde dehydrogenase 1A1 (ALDH1A1) essential survival We identified first in class ALDH1A1 inhibitor,...
Abstract Introduction: Epithelial Ovarian cancer (EOC) is one of the most fatal gynecological malignancies, with little improvement being made to early-stage diagnostics or treatment options over years. The standard care for EOC remains be platinum-based chemotherapy despite ultimate relapse which arises acquired chemoresistance. Accumulating studies show that stem-like cells (CSCs) following initial platinum contribute developed chemoresistance and metastasis. Thus, there an urgent need...
ABSTRACT High grade serous ovarian cancer (HGSOC) is the most common and aggressive type of cancer. Platinum resistance a occurrence in HGSOC main cause tumor relapse resulting high patient mortality rates. Recurrent OC enriched aldehyde dehydrogenase (ALDH)+ stem cells (OCSCs), which are resistant to platinum agents. We demonstrated that acute treatment induced DNA damage-dependent decrease BRCA1 levels. In parallel response associated with G2/M arrest, also an increase expression NAMPT ,...
Abstract Background Platinum based agents – cisplatin and carboplatin in combination with taxanes are used for the treatment of ovarian cancer (OC) patients. However, majority OC patients develop recurrent, platinum resistant disease that is uniformly fatal. Acute enriches chemoresistant aldehyde dehydrogenase (ALDH) + stem cells (OCSCs), which contribute to tumor recurrence relapse. Acquired resistance includes metabolic reprograming switching oxidative phosphorylation (OXPHOS)....
<div>Abstract<p>Aberrant silencing of genes by DNA methylation contributes to cancer, yet how this process is initiated remains unclear. Using a murine model inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment epigenetic proteins chromatin, initiating and gene in tumors. Compared with normal epithelium noninflammation-induced tumors, tumors gained at CpG islands, some which are associated putative tumor suppressor genes....
<p>Contains additional details on bioinformatic analyses, including references for packages used.</p>
<p>Supplementary Table S1: Mutational status of common oncogenes in CRC and STAD cell lines. Supplementary Figure Mutant PIK3CA does not regulate LSD1 expression. S2: DNase signal is generally depleted at TSS's, reduce global H3K4me2. S3: RCOR1 upregulated mutant versus WT cancers arising from non-gastrointestinal tissues, correlate with S4: KO reduces viability over time HT29 but SW480 cells. S5: Inhibiting AKT Snail protein level or kinase domain cells, the LSD1-AKT-GSK3b-Snail axis...
<p>RING1A monoubiquitinates phosphoH2AX at lysine 119 in response to cisplatin treatment</p>
<p>RING1A mediates monoubiquitination of phosphoH2AX in response to carboplatin</p>
<p>Rad51 colocalizes with phosphoH2AX in response to cisplatin treatment</p>
<p>Effects of CSB or XPC knockdown on platinum-induced phosphoH2AXub1</p>
<p>RING1A knockdown reduces phosphorylation of pS345 Chk1 and repair cisplatin DNA damage</p>