Sudeepa Syamala
A5054962770- Cancer, Lipids, and Metabolism
- Diet and metabolism studies
- Cancer, Hypoxia, and Metabolism
- FOXO transcription factor regulation
- Epigenetics and DNA Methylation
- Ferrocene Chemistry and Applications
- Renal and related cancers
- Ferroptosis and cancer prognosis
- Histone Deacetylase Inhibitors Research
- Estrogen and related hormone effects
- Prostate Cancer Treatment and Research
- Genomics and Chromatin Dynamics
- Metabolomics and Mass Spectrometry Studies
- Mass Spectrometry Techniques and Applications
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Liver physiology and pathology
- Infective Endocarditis Diagnosis and Management
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Neuroblastoma Research and Treatments
- RNA modifications and cancer
- Pluripotent Stem Cells Research
- RNA Research and Splicing
Dana-Farber Cancer Institute
2018-2025
Harvard University
2019-2024
German Cancer Research Center
2023
Hopp Children's Cancer Center Heidelberg
2023
Heidelberg University
2023
University of Cincinnati
2023
Sabin Vaccine Institute
2023
Boston University
2023
Broad Institute
2022
Brigham and Women's Hospital
2020-2021
A hallmark of prostate cancer progression is dysregulation lipid metabolism via overexpression fatty acid synthase (FASN), a key enzyme in de novo synthesis. Metastatic castration-resistant (mCRPC) develops resistance to inhibitors androgen receptor (AR) signaling through variety mechanisms, including the emergence constitutively active AR variant V7 (AR-V7). Here, we developed an FASN inhibitor (IPI-9119) and demonstrated that selective inhibition antagonizes CRPC growth metabolic...
Abstract Neuroendocrine carcinomas (NEC) are tumors expressing markers of neuronal differentiation that can arise at different anatomic sites but have strong histological and clinical similarities. Here we report the chromatin landscapes a range human NECs show convergence to activation common epigenetic program. With particular focus on treatment emergent neuroendocrine prostate cancer (NEPC), analyze cell lines, patient-derived xenograft (PDX) models samples existence two distinct NEPC...
Abstract c-MYC (MYC) is a major driver of prostate cancer tumorigenesis and progression. Although MYC overexpressed in both early metastatic disease associated with poor survival, its impact on transcriptional reprogramming remains elusive. We demonstrate that overexpression significantly diminishes the androgen receptor (AR) program (the set genes directly targeted by AR protein) luminal cells without altering expression. Analyses clinical specimens reveal concurrent low high programs...
Clear cell renal carcinoma (ccRCC), despite having a low mutational burden, is considered immunogenic because it occasionally undergoes spontaneous regressions and often responds to immunotherapies. The signature lesion in ccRCC inactivation of the VHL tumor suppressor gene consequent upregulation HIF transcription factor. An earlier case report described patient who was cured by an allogeneic stem transplant later found have donor-derived T cells that recognized ccRCC-specific peptide...
Abstract Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked risk prostate cancer progression mortality, but the molecular underpinnings this association poorly understood. Here, we demonstrate in a murine model, that high-fat diet (HFD) enhances MYC transcriptional program through favour histone H4K20 hypomethylation at promoter regions regulated genes, leading to cellular proliferation tumour burden. Saturated intake (SFI) is also an...
Diagnosis of prostate cancer is based on histologic evaluation tumor architecture using a system known as the "Gleason score." This diagnostic paradigm, while standard care, time-consuming, shows intraobserver variability, and provides no information about altered metabolic pathways, which result in tissue architecture. Characterization molecular composition how it changes with respect to Gleason score (GS) could enable more objective faster diagnosis. It may also aid our understanding...
Abstract Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation metabolites that reprogram tumor microenvironment (TME) and drive cancer could facilitate development precision nutrition approaches. Using Hi-MYC prostate mouse model, we demonstrated an obesogenic high-fat diet (HFD) rich in saturated fats accelerates c-MYC–driven invasive through...
Abstract Inactivation of the VHL gene stabilizes HIF2a, which drives clear cell renal carcinoma (ccRCC). The HIF2a inhibitor belzutifan is approved for ccRCC treatment, but de novo and acquired resistance are common. bound to ARNT, transcriptionally activates many genes. We performed CRISPRa screens in HIF2a-dependent lines treated with a analog identify HIF2a-responsive genes that confer cell-autonomous when not downregulated. Sustaining expression target CCND1, encoding Cyclin D1, promoted...
Abstract Forkhead box R2 (FOXR2) is a forkhead transcription factor located on the X chromosome whose expression normally restricted to testis. In this study, we performed pan-cancer analysis of FOXR2 activation across more than 10,000 adult and pediatric cancer samples found be aberrantly upregulated in 70% all types 8% individual tumors. The majority tumors (78%) expressed through previously undescribed epigenetic mechanism that involves hypomethylation novel promoter, which was...
Abstract Most invasive lobular breast cancers (ILC) are of the luminal A subtype and strongly hormone receptor–positive. Yet, ILC is relatively resistant to tamoxifen associated with inferior long-term outcomes compared ductal (IDC). In this study, we sought gain mechanistic insights into these clinical findings that not explained by genetic landscape identify strategies improve patient outcomes. comprehensive analysis epigenome in preclinical models samples showed that, IDC, harbored a...
Abstract Neuroendocrine carcinomas (NEC) are tumors expressing markers of neuronal differentiation that can arise at different anatomic sites but have strong histological and clinical similarities. Here we report the chromatin landscapes a range human NECs show convergence to activation common epigenetic program. With particular focus on treatment emergent neuroendocrine prostate cancer (NEPC), analyzed cell lines, patient-derived xenograft (PDX) models samples existence two distinct NEPC...
<p>Supplementary Figure S7 shows the output of mouse-based deconvolution models ImmuCC and mMCP.</p>
<p>Supplementary Figure S2 shows the effect of obesogenic HFD on AP and VP lobes, cell proliferation rate in MYC-transformed DLP, WT prostate lobes.</p>
<p>Supplementary Figure S1 shows the systemic effects of HFD.</p>
<p>Supplementary Figure S2 shows the effect of obesogenic HFD on AP and VP lobes, cell proliferation rate in MYC-transformed DLP, WT prostate lobes.</p>
<p>Supplementary Figure S6 includes scRNA-seq data showing that Luminal (high Ly6d) cells in MYC-transformed DLP display glycolytic features.</p>
<p>Supplementary Figure S5 shows the output of ESTIMATE and PUREE methods to assess tumor purity.</p>
<p>Supplementary Figure S4 shows the effect of obesogenic high-fat diet on glycolytic enzymes and HIF-1 alpha in vivo.</p>
<div>Abstract<p>Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation metabolites that reprogram tumor microenvironment (TME) and drive cancer could facilitate development precision nutrition approaches. Using Hi-MYC prostate mouse model, we demonstrated an obesogenic high-fat diet (HFD) rich in saturated fats accelerates c-MYC–driven...
<p>Supplementary Figure S3 shows a graphical representation of key metabolic pathways altered by MYC alone or obesogenic HFD in WT and MYC-transformed DLP.</p>
<p>Supplementary Figure S10 shows the output of human-based deconvolution model QuanTIseq.</p>
<p>Supplementary Figure S1 shows the systemic effects of HFD.</p>
<p>Supplementary Figure S6 includes scRNA-seq data showing that Luminal (high Ly6d) cells in MYC-transformed DLP display glycolytic features.</p>