Darshan S. Chandrashekar

ORCID: 0000-0002-4295-9127
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About
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Research Areas
  • Mechanisms of cancer metastasis
  • Epigenetics and DNA Methylation
  • RNA modifications and cancer
  • Ferroptosis and cancer prognosis
  • Cancer Research and Treatments
  • Cancer Genomics and Diagnostics
  • Cancer, Hypoxia, and Metabolism
  • Cancer-related molecular mechanisms research
  • RNA Research and Splicing
  • Bladder and Urothelial Cancer Treatments
  • Cancer-related gene regulation
  • Renal cell carcinoma treatment
  • Ubiquitin and proteasome pathways
  • Protein Degradation and Inhibitors
  • Bioinformatics and Genomic Networks
  • Histone Deacetylase Inhibitors Research
  • Chemical Reactions and Isotopes
  • Silkworms and Sericulture Research
  • Cancer, Lipids, and Metabolism
  • Genetic factors in colorectal cancer
  • RNA and protein synthesis mechanisms
  • Molecular Biology Techniques and Applications
  • Plant Pathogenic Bacteria Studies
  • Gene expression and cancer classification
  • MicroRNA in disease regulation

University of Alabama at Birmingham
2016-2025

Institute of Bioinformatics and Applied Biotechnology
2010-2023

O'Neal Comprehensive Cancer Center
2022

University of Alabama
2018

Biotech Park
2010-2015

Manipal Academy of Higher Education
2014-2015

Central Sericultural Research and Training Institute
1999-2008

Genomics data from The Cancer Genome Atlas (TCGA) project has led to the comprehensive molecular characterization of multiple cancer types. large sample numbers in TCGA offer an excellent opportunity address questions associated with tumo heterogeneity. Exploration by researchers and clinicians is imperative unearth novel therapeutic/diagnostic biomarkers. Various computational tools have been developed aid carrying out specific analyses; however there need for resources facilitate study...

10.1016/j.neo.2017.05.002 article EN cc-by-nc-nd Neoplasia 2017-07-18

Cancer genomic, transcriptomic, and proteomic profiling has generated extensive data that necessitate the development of tools for its analysis dissemination. We developed UALCAN to provide a portal easy exploring, analyzing, visualizing these data, allowing users integrate better understand gene, proteins, pathways perturbed in cancer make discoveries. web enables analyzing delivering transcriptome, proteomics, patient survival research community. With obtained from The Genome Atlas (TCGA)...

10.1016/j.neo.2022.01.001 article EN cc-by-nc-nd Neoplasia 2022-01-22

Abstract Mass-spectrometry-based proteomic profiling of human cancers has the potential for pan-cancer analyses to identify molecular subtypes and associated pathway features that might be otherwise missed using transcriptomics. Here, we classify 532 cancers, representing six tissue-based types (breast, colon, ovarian, renal, uterine), into ten proteome-based, cut across tumor lineages. The proteome-based are observable in external cancer datasets surveyed. Gene signatures oncogenic or...

10.1038/s41467-019-13528-0 article EN cc-by Nature Communications 2019-12-12

The heparan sulfate-degrading enzyme heparanase promotes the progression of many cancers by driving tumor cell proliferation, metastasis and angiogenesis. Heparanase accomplishes this via multiple mechanisms including its recently described effect on enhancing biogenesis exosomes. Because we discovered that expression is upregulated in myeloma cells survive chemotherapy, were prompted to investigate impact anti-myeloma drugs exosome biogenesis. When exposed commonly utilized bortezomib,...

10.1016/j.matbio.2017.09.001 article EN cc-by-nc-nd Matrix Biology 2017-09-06

Abstract Mass-spectrometry-based proteomic data on human tumors—combined with corresponding multi-omics data—present opportunities for systematic and pan-cancer proteogenomic analyses. Here, we assemble a compendium dataset of proteomics 2002 primary tumors from 14 cancer types 17 studies. Protein expression genes broadly correlates mRNA levels or copy number alterations (CNAs) across tumors, but notable exceptions. Based unsupervised clustering, separate into 11 distinct proteome-based...

10.1038/s41467-022-30342-3 article EN cc-by Nature Communications 2022-05-13

Despite the prevalence and recognition of its detrimental impact, clinical complications sepsis remain a major challenge. Here, we investigated effects myeloid ferritin heavy chain (FtH) in regulating pathogenic sequelae sepsis. We demonstrate that deletion FtH leads to protection against lipopolysaccharide-induced endotoxemia cecal ligation puncture (CLP)-induced model as evidenced by reduced cytokine levels, multi-organ dysfunction mortality. identified such is predominantly mediated...

10.3389/fimmu.2019.00131 article EN cc-by Frontiers in Immunology 2019-02-03

Metastatic urothelial carcinoma is generally incurable with current systemic therapies. Chromatin modifiers are frequently mutated in bladder cancer, ARID1A-inactivating mutations present about 20% of tumors. EZH2, a histone methyltransferase, acts as an oncogene that functionally opposes ARID1A. In addition, PI3K signaling activated more than cancers. Using combination vitro and vivo data, including patient-derived xenografts, we show ARID1A-mutant tumors were sensitive to EZH2 inhibition...

10.1172/jci.insight.155899 article EN cc-by JCI Insight 2022-07-19

Therapeutic interventions that counter emerging targets in diabetes eye diseases are lacking. We hypothesize a combination therapy targeting inflammation and hyperglycemia can prevent diabetic diseases. Here, we report multipronged approach to cataracts retinopathy by combining orally bioavailable curcumin-laden double-headed (two molecules of gambogic acid conjugated terminal carboxyl groups poly(d,l-lactide-co-glycolide)) nanoparticles injectable basal insulin. The treatment led...

10.1021/acsnano.3c00535 article EN ACS Nano 2023-03-23

Breast cancer (BCa), a leading malignancy among women, is characterized by morphological and molecular heterogeneity. While early-stage, hormone receptor, HER2-positive BCa are treatable, triple-negative metastatic remains largely untreatable. Advances in sequencing proteomic technologies have improved our understanding of the alterations that occur during initiation progression enabled identification subclass-specific biomarkers therapeutic targets. Despite availability abundant omics data...

10.1038/s41523-025-00750-x article EN cc-by-nc-nd npj Breast Cancer 2025-04-18

Host responses to tumor cells include suppressing or promoting mechanisms. We sought detail the effect of Hedgehog (Hh) pathway inhibition on composition mammary immune portfolio. hypothesized that Hh signaling mediates a crosstalk between breast cancer and macrophages dictates alternative polarization consequently supports tumor-promoting microenvironment. used an immunocompetent, syngeneic mouse model inhibit with pharmacological inhibitor, Vismodegib. Using molecular functional assays, we...

10.1080/2162402x.2018.1548241 article EN OncoImmunology 2018-12-12

MicroRNA-101, a tumor suppressor microRNA (miR), is often downregulated in cancer and known to target multiple oncogenes. Some of the genes that are negatively regulated by miR-101 expression include histone methyltransferase EZH2 (enhancer zeste homolog 2), COX2 (cyclooxygenase-2), POMP (proteasome maturation protein), CERS6, STMN1, MCL-1 ROCK2, among others. In present study, we show targets transcriptional coactivator SUB1 (Saccharomyces cerevisiae)/PC4 (positive cofactor 4) regulates its...

10.1038/onc.2016.164 article EN cc-by Oncogene 2016-06-06

Background African Americans (AAs) experience a disproportionally high rate of bladder cancer (BLCA) deaths even though their incidence rates are lower than those other patient groups. Using metabolomics approach, this study investigated how AA BLCA may differ molecularly from European (EAs) BLCA, and it examined serum samples patients with the aim identifying druggable metabolic pathways in patients. Methods Targeted was applied to measure more 300 metabolites 2 independent cohorts EA...

10.1002/cncr.31890 article EN Cancer 2019-01-02

Thyroid receptor‐interacting protein 13 (TRIP13), a of the AAA‐ATPase family, is upregulated in various human cancers, including colorectal cancer (CRC). This study focused on inhibition TRIP13‐induced CRC progression and signalling by DCZ0415, small molecule targeting TRIP13. It demonstrated potent antitumour activity TRIP13‐deregulated cell lines, regardless their p53, KRAS, BRAF, epidermal growth factor receptor or microsatellite instability status. The treatment cells with DCZ0415...

10.1002/1878-0261.13201 article EN cc-by Molecular Oncology 2022-02-23

Abstract Both proteome and transcriptome data can help assess the relevance of non-coding somatic mutations in cancer. Here, we combine mass spectrometry-based proteomics with whole genome sequencing across 1307 human tumors spanning various tissues to determine extent structural variant (SV) breakpoint patterns impact protein expression nearby genes. We find that about 25% hundreds genes SV-associated cis-regulatory alterations at mRNA level are similarly associated level. SVs enhancer...

10.1038/s41467-023-41374-8 article EN cc-by Nature Communications 2023-09-13

Abstract Background Treatment with regorafenib, a multiple-kinase inhibitor, to manage metastatic colorectal cancers (mCRCs) shows modest improvement in overall survival but is associated severe toxicities. Thus, reduce regorafenib-induced toxicity, we used regorafenib at low concentration along dual JAK/HDAC small-molecule inhibitor (JAK/HDACi) leverage the advantages of both JAK and HDAC inhibition enhance antitumor activity. The therapeutic efficacy safety combination treatment was...

10.1186/s13046-024-03106-8 article EN cc-by Journal of Experimental & Clinical Cancer Research 2024-07-11

Background Endometrium acquires structural and functional competence for embryo implantation only during the receptive phase of menstrual cycle in fertile women. Sizeable data are available to indicate that this ability is acquired by modulation expression several genes/gene products. However, there exists little consensus on identity, number expressed/not-detected genes their pattern (up or down regulation). Methods Literature search was carried out retrieve endometrial genes/proteins...

10.1371/journal.pone.0058419 article EN cc-by PLoS ONE 2013-03-26

Abstract In aggressive prostate cancers, the oncoprotein STMN1 (also known as stathmin 1 and 18) is often overexpressed. involved in various cellular processes, including cell proliferation, motility, tumor metastasis. Here, it was found that expression of RNA protein elevated metastatic cancers. Knockdown resulted reduced proliferation invasion cells growth metastasis vivo. Furthermore, miR-34a downregulated by directly binding to its 3′-UTR. Overexpression cancer colony formation,...

10.1158/1541-7786.mcr-17-0230 article EN Molecular Cancer Research 2017-10-13

Genomic and transcriptome sequencing of bladder cancer (BLCA) has identified multiple molecular alterations during progression. Many these genetic epigenetic changes play a role in the progression this disease. Studies have subtypes muscle-invasive (MIBC) with different sensitivities to frontline therapy suggesting heterogeneity tumors importance characterization MIBC provide effective treatment. Specifically, it become increasingly evident, as demonstrated by The Cancer Genome Atlas...

10.1016/j.neo.2018.07.006 article EN cc-by-nc-nd Neoplasia 2018-08-15

The identification of colorectal cancer (CRC) molecular targets is needed for the development drugs that improve patient survival. We investigated functional role phosphoribosylaminoimidazole carboxylase, succinocarboxamide synthetase (PAICS), a de novo purine biosynthetic enzyme involved in DNA synthesis, CRC progression and metastasis by using cell animal models. Its clinical utility was assessed human samples. expression PAICS regulated miR-128 transcriptionally activated Myc cells....

10.3390/cancers12040772 article EN Cancers 2020-03-25

Overexpression of TRIP13, a member the AAA‐ATPase family, is linked with various cancers, but its role in metastasis unknown colorectal cancer (CRC). In current study, we investigated TRIP13 experimental and involvement regulation WNT/β‐catenin EGFR signaling pathways. Evaluation formalin‐fixed paraffin‐embedded (FFPE) frozen tissues adenomas CRCs, along their corresponding normal samples, showed that was gradually increased phenotypic expression from adenoma to carcinoma overexpression CRCs...

10.1002/1878-0261.12821 article EN cc-by Molecular Oncology 2020-10-10

Analysis of transcriptomic data demonstrates extensive epigenetic gene silencing the transcription factor PRDM16 in renal cancer. We show that restoration RCC cells suppresses vivo tumor growth. RNaseq analysis reveals imparts a predominantly repressive effect on transcriptome including suppression encoding semaphorin 5B (SEMA5B). SEMA5B is HIF target highly expressed promotes Functional studies demonstrate PRDM16's properties, mediated by physical interaction with transcriptional...

10.1084/jem.20191005 article EN cc-by-nc-sa The Journal of Experimental Medicine 2020-04-06

Our goal was to investigate de novo purine biosynthetic gene PAICS expression and evaluate its role in prostate cancer progression.Next-generation sequencing, qRTPCR immunoblot analysis revealed an elevated of a gene, Phosphoribosylaminoimidazole Carboxylase, Succinocarboxamide Synthetase (PAICS) progressive manner cancer. Functional analyses were performed using cell lines- DU145, PC3, LnCaP, VCaP. The oncogenic properties studied both by transient stable knockdown strategies, vivo chicken...

10.1002/pros.23243 article EN The Prostate 2016-08-22
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