Scholars@Duke
Jen-Tsan Ashley Chi

Jen-Tsan Ashley Chi

Professor in Molecular Genetics and Microbiology
Molecular Genetics and Microbiology
jentsan.chi@duke.edu
Duke Box 3382, Durham, NC 27710
101 Science Dr, DUMC3382, Room 2177A, CIEMAS Bldg, Durham, NC 27708

Selected Publications

Optimized Monothiol Thioredoxin Derivative (ORP100S) Protects In Vitro and In Vivo from Radiation and Chemotoxicity Without Promoting Tumor Proliferation.

Journal Article Adv Sci (Weinh) · November 2025 Human thioredoxin-1 (TRX) is a target-selective disulfide reductase with antioxidant, anti-inflammatory, and regulatory functions that mitigates cellular stresses in various organ systems, providing a compelling rationale for therapeutic use as a broad-spe ... Full text Open Access Link to item Cite

Coenzyme A protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase.

Journal Article J Clin Invest · October 1, 2025 The cystine-xCT transporter/glutathione/GPX4 axis is the canonical pathway protecting cells from ferroptosis. Whereas GPX4-targeting ferroptosis-inducing compounds (FINs) act independently of mitochondria, xCT-targeting FINs require mitochondrial lipid per ... Full text Link to item Cite

Target sequence-conditioned design of peptide binders using masked language modeling.

Journal Article Nat Biotechnol · August 13, 2025 The computational design of protein-based binders presents unique opportunities to access 'undruggable' targets, but effective binder design often relies on stable three-dimensional structures or structure-influenced latent spaces. Here we introduce PepMLM ... Full text Link to item Cite

Evidence for functional regulation of the KLHL3/WNK pathway by O-GlcNAcylation.

Journal Article Glycobiology · August 11, 2025 The 42-member Kelch-like (KLHL) protein family are adaptors for ubiquitin E3 ligase complexes, governing the stability of a wide range of substrates. KLHL proteins are critical for maintaining proteostasis in a variety of tissues and are mutated in human d ... Full text Link to item Cite

Evidence for Functional Regulation of the KLHL3/WNK Pathway by O-GlcNAcylation.

Journal Article bioRxiv · February 27, 2025 The 42-member Kelch-like (KLHL) protein family are adaptors for ubiquitin E3 ligase complexes, governing the stability of a wide range of substrates. KLHL proteins are critical for maintaining proteostasis in a variety of tissues and are mutated in human d ... Full text Link to item Cite

NINJ1 in Cell Death and Ferroptosis: Implications for Tumor Invasion and Metastasis.

Journal Article Cancers (Basel) · February 26, 2025 NINJ1 was initially recognized for its role in nerve regeneration and cellular adhesion. Subsequent studies have uncovered its participation in cancer progression, where NINJ1 regulates critical steps in tumor metastasis, such as cell migration and invasio ... Full text Link to item Cite

Targeting the ferroptosis pathway: A novel compound, AZD1390, protects the brain after ischemic stroke.

Journal Article bioRxiv · February 25, 2025 BACKGROUND: Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation. This process has been implicated in various diseases, including ischemic stroke. Ischemic stroke leads to oxidative stress, iron overload, and reactive ... Full text Link to item Cite

Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.

Journal Article Proc Natl Acad Sci U S A · January 7, 2025 Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatment ... Full text Link to item Cite

CTNI-64. TRIAL IN PROGRESS: DIET2TREAT -- A RANDOMIZED MULTICENTER PHASE 2 TRIAL OF A KETOGENIC DIET VS STANDARD DIETARY GUIDANCE IN COMBINATION WITH STANDARD-OF-CARE TREATMENT FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Conference Neuro-Oncology · November 11, 2024 AbstractBACKGROUNDMany glioblastoma (GBM) patients inquire about the potential therapeutic benefits of a high fat / low carbohydrate k ... Full text Cite

NINJ1 regulates ferroptosis via xCT antiporter interaction and CoA modulation.

Journal Article Cell Death Dis · October 18, 2024 Ninjurin-1 (NINJ1), initially identified as a stress-induced protein in neurons, recently emerged as a key mediator of plasma membrane rupture (PMR) during apoptosis, necrosis, and pyroptosis. However, its involvement in ferroptosis is less well elucidated ... Full text Link to item Cite

A guideline on the molecular ecosystem regulating ferroptosis.

Journal Article Nat Cell Biol · September 2024 Ferroptosis, an intricately regulated form of cell death characterized by uncontrolled lipid peroxidation, has garnered substantial interest since this term was first coined in 2012. Recent years have witnessed remarkable progress in elucidating the detail ... Full text Link to item Cite

International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis.

Journal Article Autophagy · June 2024 Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characteriz ... Full text Link to item Cite

Metabolic Response to Androgen Deprivation Therapy of Prostate Cancer.

Journal Article Cancers (Basel) · May 24, 2024 Prostate cancer (PC) stands as the most frequently diagnosed non-skin cancer and ranks as the second highest cause of cancer-related deaths among men in the United States. For those facing non-metastatic PC necessitating intervention, solely local treatmen ... Full text Link to item Cite

Sucrose Treatment Enhances the Electrotransfer of DNA by Activating Phospholipase A2.

Journal Article Pharmaceutics · March 29, 2024 Our previous study discovered that sucrose and other non-reducing sugars (e.g., trehalose and raffinose) could be used to improve the electrotransfer (ET) of molecular cargo, including DNA, mRNA, and ribonucleoprotein in various cell lines and primary huma ... Full text Link to item Cite

Abstract 359: The Hippo pathway on breast tumor recurrence <and> collateral vulnerability to ferroptosis

Conference Cancer Research · March 22, 2024 AbstractComparing with primary breast tumors, recurrent breast cancers are generally considered more aggressive and incurable. Therefore, novel molecular strategies are urgently needed to target these type o ... Full text Cite

Novel anti-inflammatory effects of the IL-1 receptor in kidney myeloid cells following ischemic AKI.

Journal Article Front Mol Biosci · 2024 Introduction: Acute kidney injury (AKI) is one of the most common causes of organ failure in critically ill patients. Following AKI, the canonical pro-inflammatory cytokine interleukin-1β (IL-1β) is released predominantly from activated myeloid cells and b ... Full text Link to item Cite

O-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations.

Journal Article Nat Commun · October 17, 2023 The neurofilament (NF) cytoskeleton is critical for neuronal morphology and function. In particular, the neurofilament-light (NF-L) subunit is required for NF assembly in vivo and is mutated in subtypes of Charcot-Marie-Tooth (CMT) disease. NFs are highly ... Full text Link to item Cite

Environmental Determinants of Ferroptosis in Cancer.

Journal Article Cancers (Basel) · July 29, 2023 Given the enormous suffering and death associated with human cancers, there is an urgent need for novel therapeutic approaches to target tumor growth and metastasis. While initial efforts have focused on the dysregulated oncogenic program of cancer cells, ... Full text Link to item Cite

Targeting YAP-mediated HSC death susceptibility and senescence for treatment of liver fibrosis.

Conference Hepatology · June 1, 2023 BACKGROUND AND AIMS: Liver fibrosis results from the accumulation of myofibroblasts (MFs) derived from quiescent HSCs, and yes-associated protein (YAP) controls this state transition. Although fibrosis is also influenced by HSC death and senescence, whethe ... Full text Open Access Link to item Cite

Data on the transcriptional response to MESH1 knockdown and mammalian stringent response.

Journal Article Data Brief · April 2023 MESH1 is the metazoan homolog of bacterial SpoT, the main phosphatase that dephosphorylates and degrades (p)ppGpp, the alarmone involved in the bacterial stringent response. The functional role of MESH1 in human cells is unknown. To define the global trans ... Full text Link to item Cite

Manassantin A inhibits tumour growth under hypoxia through the activation of chaperone-mediated autophagy by modulating Hsp90 activity.

Journal Article Br J Cancer · April 2023 BACKGROUND: Chaperon-mediated autophagy (CMA) has taken on a new emphasis in cancer biology. However, the roles of CMA in hypoxic tumours are poorly understood. We investigated the anti-tumour effects of the natural product ManA through the activation of C ... Full text Link to item Cite

Peritoneal Tumor Microenvironment Labchip For The Selection Of Hipec Drugs

Conference 2023 22nd International Conference on Solid State Sensors Actuators and Microsystems Transducers 2023 · January 1, 2023 Cancer is the leading cause of death worldwide, and therapies to overcome cancer metastasis and cell proliferation are challenging. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is often a last resort. Our goal is to develop a platform for HIPEC drug s ... Cite

A Labchip with Co-Cultured Spheroids Applied for HIPEC Cancer Drug Screening

Conference 2023 22nd International Conference on Solid State Sensors Actuators and Microsystems Transducers 2023 · January 1, 2023 Cancer has always been one of the health issues of concern to all walks of life. The reason why cancer is difficult to cure is that cancer cells will metastasize or spread to other parts of the body. However, the cancer cells in the abdominal cavity of pat ... Cite

Ferroptosis and Infectious Diseases

Chapter · January 1, 2023 Ferroptosis is a newly recognized form of regulated cell death characterized by oxidative stress, iron dependency, and lipid peroxidation. The importance of ferroptosis has been appreciated in various pathological conditions, such as cancer, neurodegenerat ... Full text Cite

Parkin coordinates mitochondrial lipid remodeling to execute mitophagy.

Journal Article EMBO Rep · December 6, 2022 Autophagy has emerged as the prime machinery for implementing organelle quality control. In the context of mitophagy, the ubiquitin E3 ligase Parkin tags impaired mitochondria with ubiquitin to activate autophagic degradation. Although ubiquitination is es ... Full text Open Access Link to item Cite

Identification and targeting of a HES1-YAP1-CDKN1C functional interaction in fusion-negative rhabdomyosarcoma.

Journal Article Mol Oncol · October 2022 Rhabdomyosarcoma (RMS), a cancer characterized by features of skeletal muscle, is the most common soft-tissue sarcoma of childhood. With 5-year survival rates among high-risk groups at < 30%, new therapeutics are desperately needed. Previously, usin ... Full text Link to item Cite

Serum metabolomic analysis of men on a low-carbohydrate diet for biochemically recurrent prostate cancer reveals the potential role of ketogenesis to slow tumor growth: a secondary analysis of the CAPS2 diet trial.

Journal Article Prostate Cancer Prostatic Dis · April 2022 BACKGROUND: Systemic treatments for prostate cancer (PC) have significant side effects. Thus, newer alternatives with fewer side effects are urgently needed. Animal and human studies suggest the therapeutic potential of low carbohydrate diet (LCD) for PC. ... Full text Open Access Link to item Cite

MESH1 knockdown triggers proliferation arrest through TAZ repression.

Journal Article Cell Death Dis · March 10, 2022 All organisms are constantly exposed to various stresses, necessitating adaptive strategies for survival. In bacteria, the main stress-coping mechanism is the stringent response triggered by the accumulation of "alarmone" (p)ppGpp to arrest proliferation a ... Full text Link to item Cite

Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer.

Journal Article Mol Ther · January 5, 2022 Serine/threonine kinase 3 (STK3) is an essential member of the highly conserved Hippo tumor suppressor pathway that regulates Yes-associated protein 1 (YAP1) and TAZ. STK3 and its paralog STK4 initiate a phosphorylation cascade that regulates YAP1/TAZ inhi ... Full text Link to item Cite

Serum metabolomic analysis of men on a low-carbohydrate diet for biochemically recurrent prostate cancer reveal the potential role of ketogenesis to slow tumor growth: A secondary analysis of the CAPS2 diet trial

Journal Article · 2022 Background Systemic treatments for prostate cancer (PC) have significant side effects. Thus, newer alternatives with fewer side effects are urgently needed. Animal and human studies suggest the therapeutic potential of low carbohydrate diet (LCD) ... Full text Cite

Single Cell RNA-Seq Analysis of Human Red Cells.

Journal Article Front Physiol · 2022 Human red blood cells (RBCs), or erythrocytes, are the most abundant blood cells responsible for gas exchange. RBC diseases affect hundreds of millions of people and impose enormous financial and personal burdens. One well-recognized, but poorly understood ... Full text Link to item Cite

Metazoan stringent-like response mediated by MESH1 phenotypic conservation via distinct mechanisms.

Journal Article Comput Struct Biotechnol J · 2022 All organisms are constantly exposed to various stresses, necessitating adaptive strategies for survival. In bacteria, the main metabolic stress-coping mechanism is the stringent response, which is triggered by the accumulation of "alarmone" (p)ppGpp to ar ... Full text Link to item Cite

Biomimetic polydopamine-laced hydroxyapatite collagen material orients osteoclast behavior to an anti-resorptive pattern without compromising osteoclasts' coupling to osteoblasts.

Journal Article Biomater Sci · November 9, 2021 Polydopamine-assisted modification for bone substitute materials has recently shown great application potential in bone tissue engineering due to its excellent biocompatibility and adhesive properties. A scaffold material's impact on osteoclasts is equally ... Full text Link to item Cite

Single Cell Analysis of Stored Red Blood Cells Using Ultra-High Throughput Holographic Cytometry.

Journal Article Cells · September 17, 2021 Holographic cytometry is introduced as an ultra-high throughput implementation of quantitative phase imaging of single cells flowing through parallel microfluidic channels. Here, the approach was applied for characterizing the morphology of individual red ... Full text Link to item Cite

Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells but exacerbates chronic liver injury.

Journal Article Liver Int · September 2021 BACKGROUND & AIMS: The outcome of liver injury is dictated by factors that control the accumulation of myofibroblastic (activated) hepatic stellate cells (MF-HSCs) but therapies that specifically block this process have not been discovered. We evaluated th ... Full text Link to item Cite

The regulation of ferroptosis by MESH1 through the activation of the integrative stress response.

Journal Article Cell Death Dis · July 22, 2021 All organisms exposed to metabolic and environmental stresses have developed various stress adaptive strategies to maintain homeostasis. The main bacterial stress survival mechanism is the stringent response triggered by the accumulation "alarmone" (p)ppGp ... Full text Link to item Cite

The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling.

Journal Article Nat Commun · July 14, 2021 Hypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this stud ... Full text Link to item Cite

The influence of low-carbohydrate diets on the metabolic response to androgen-deprivation therapy in prostate cancer.

Journal Article Prostate · July 2021 BACKGROUND: Prostate cancer (PC) is the second most lethal cancer for men. For metastatic PC, standard first-line treatment is androgen deprivation therapy (ADT). While effective, ADT has many metabolic side effects. Previously, we found in serum metabolom ... Full text Link to item Cite

The Hippo Pathway Effector YAP Promotes Ferroptosis via the E3 Ligase SKP2.

Journal Article Mol Cancer Res · June 2021 Ferroptosis is a new form of regulated cell death resulting from the accumulation of lipid-reactive oxygen species. A growing number of studies indicate ferroptosis as an important tumor suppressor mechanism having therapeutic potential in cancers. Previou ... Full text Open Access Link to item Cite

Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications.

Journal Article Genes Dis · May 2021 Ferroptosis is a novel form of iron-dependent cell death characterized by lipid peroxidation. While the importance and disease relevance of ferroptosis is gaining recognition, much remains unknown about various genetic and non-genetic determinants of ferro ... Full text Link to item Cite

DDR2 upregulation confers ferroptosis susceptibility of recurrent breast tumors through the Hippo pathway.

Journal Article Oncogene · March 2021 Recurrent breast cancer presents significant challenges with aggressive phenotypes and treatment resistance. Therefore, novel therapeutics are urgently needed. Here, we report that murine recurrent breast tumor cells, when compared with primary tumor cells ... Full text Open Access Link to item Cite

Zinc transporter ZIP7 is a novel determinant of ferroptosis.

Journal Article Cell Death Dis · February 19, 2021 Ferroptosis is a newly described form of regulated cell death triggered by oxidative stresses and characterized by extensive lipid peroxidation and membrane damages. The name of ferroptosis indicates that the ferroptotic death process depends on iron, but ... Full text Open Access Link to item Cite

A method to culture human alveolar rhabdomyosarcoma cell lines as rhabdospheres demonstrates an enrichment in stemness and Notch signaling.

Journal Article Biol Open · February 9, 2021 The development of three-dimensional cell culture techniques has allowed cancer researchers to study the stemness properties of cancer cells in in vitro culture. However, a method to grow PAX3-FOXO1 fusion-positive rhabdomyosarcoma (FP-RMS), an aggressive ... Full text Link to item Cite

Application of bioluminescence resonance energy transfer-based cell tracking approach in bone tissue engineering.

Journal Article J Tissue Eng · 2021 Bioluminescent imaging (BLI) has emerged as a popular in vivo tracking modality in bone regeneration studies stemming from its clear advantages: non-invasive, real-time, and inexpensive. We recently adopted bioluminescence resonance energy transfer (BRET) ... Full text Open Access Link to item Cite

Characterizing stored red blood cells using ultra-high throughput holographic cytometry

Journal Article · 2021 Holographic cytometry is introduced as an ultra-high throughput implementation of quantitative phase image based on off-axis interferometry of cells flowing through parallel microfluidic channels. Here, it is applied for characterizing morphological change ... Full text Cite

Editorial: Novel Insights Into Ferroptosis.

Journal Article Front Cell Dev Biol · 2021 Full text Link to item Cite

G9a Promotes Breast Cancer Recurrence through Repression of a Pro-inflammatory Program.

Journal Article Cell Rep · November 3, 2020 Dysregulated gene expression is a common feature of cancer and may underlie some aspects of tumor progression, including tumor relapse. Here, we show that recurrent mammary tumors exhibit global changes in gene expression and histone modifications and acqu ... Full text Link to item Cite

Ferroptosis of epithelial ovarian cancer: genetic determinants and therapeutic potential.

Journal Article Oncotarget · September 29, 2020 Epithelial ovarian cancer (OVCA) is the most lethal gynecologic cancer. Current treatment for OVCA involves surgical debulking of the tumors followed by combination chemotherapies. While most patients achieve complete remission, many OVCA will recur and de ... Full text Link to item Cite

The effects of low-carbohydrate diets on the metabolic response to androgen-deprivation therapy in prostate cancer

Journal Article · September 25, 2020 Prostate cancer (PC) is the second most lethal cancer for men and metastatic PC is treated by androgen deprivation therapy (ADT). While effective, ADT has many metabolic side effects. Previously, serum metabolome analysis showed that ADT reduced androstero ... Full text Cite

The Intersection of DNA Damage Response and Ferroptosis-A Rationale for Combination Therapeutics.

Journal Article Biology (Basel) · July 23, 2020 Ferroptosis is a novel form of iron-dependent cell death characterized by lipid peroxidation. While the importance and disease relevance of ferroptosis are gaining recognition, much remains unknown about its interaction with other biological processes and ... Full text Open Access Link to item Cite

RIPK3 upregulation confers robust proliferation and collateral cystine-dependence on breast cancer recurrence.

Journal Article Cell Death Differ · July 2020 The molecular and genetic basis of tumor recurrence is complex and poorly understood. RIPK3 is a key effector in programmed necrotic cell death and, therefore, its expression is frequently suppressed in primary tumors. In a transcriptome profiling between ... Full text Link to item Cite

Metabolomic effects of androgen deprivation therapy treatment for prostate cancer.

Journal Article Cancer Med · June 2020 Androgen deprivation therapy (ADT) is the main treatment strategy for men with metastatic prostate cancer (PC). However, ADT is associated with various metabolic disturbances, including impaired glucose tolerance, insulin resistance and weight gain, increa ... Full text Link to item Cite

27-Hydroxycholesterol Impairs Plasma Membrane Lipid Raft Signaling as Evidenced by Inhibition of IL6-JAK-STAT3 Signaling in Prostate Cancer Cells.

Journal Article Mol Cancer Res · May 2020 We recently reported that restoring the CYP27A1-27hydroxycholesterol axis had antitumor properties. Thus, we sought to determine the mechanism by which 27HC exerts its anti-prostate cancer effects. As cholesterol is a major component of membrane microdomai ... Full text Link to item Cite

Kelch‐like Proteins Have A Sweet Spot: Site‐specific Glycosylation Influences Metabolic Regulation and Protein Homeostasis

Conference The FASEB Journal · April 2020 The Kelch‐like (KLHL) family of proteins, a conserved group of 42 human members, binds to E3 ubiquitin ligase complexes to target protein substrates for proteas ... Full text Cite

Kinome screen of ferroptosis reveals a novel role of ATM in regulating iron metabolism.

Journal Article Cell Death Differ · March 2020 Ferroptosis is a specialized iron-dependent cell death that is associated with lethal lipid peroxidation. Modulation of ferroptosis may have therapeutic potential since it has been implicated in various human diseases as well as potential antitumor activit ... Full text Open Access Link to item Cite

MESH1 is a cytosolic NADPH phosphatase that regulates ferroptosis.

Journal Article Nat Metab · March 2020 Critical to the bacterial stringent response is the rapid relocation of resources from proliferation toward stress survival through the respective accumulation and degradation of (p)ppGpp by RelA and SpoT homologues. While mammalian genomes encode MESH1, a ... Full text Open Access Link to item Cite

Gigaxonin glycosylation regulates intermediate filament turnover and may impact giant axonal neuropathy etiology or treatment.

Journal Article JCI Insight · January 16, 2020 Gigaxonin (also known as KLHL16) is an E3 ligase adaptor protein that promotes the ubiquitination and degradation of intermediate filament (IF) proteins. Mutations in human gigaxonin cause the fatal neurodegenerative disease giant axonal neuropathy (GAN), ... Full text Link to item Cite

A TAZ-ANGPTL4-NOX2 Axis Regulates Ferroptotic Cell Death and Chemoresistance in Epithelial Ovarian Cancer.

Journal Article Mol Cancer Res · January 2020 Ovarian cancer is the deadliest gynecologic cancer. Despite recent advances, clinical outcomes remain poor, necessitating novel therapeutic approaches. To investigate metabolic susceptibility, we performed nutrigenetic screens on a panel of clear cell and ... Full text Link to item Cite

Hippo pathway effectors YAP/TAZ as novel determinants of ferroptosis.

Journal Article Mol Cell Oncol · 2020 Ferroptosis is a novel form of programmed cell death. We found that the ferroptosis sensitivity in renal and ovarian cancers are regulated by cell density through TAZ-EMP1-NOX4 and TAZ-ANGPTL4-NOX2 pathway, respectively. These findings reveal TAZ as a nove ... Full text Link to item Cite

G9a Promotes Breast Cancer Recurrence Through Repression of a Pro-inflammatory Program

Journal Article · 2020 Epigenetic dysregulation is a common feature of cancer, and is thought to underlie many aspects of tumor progression. Using a genetically engineered mouse model of breast cancer recurrence, we show that recurrent mammary tumors undergo widespread epigenomi ... Full text Cite

Parkin coordinates mitochondrial lipid remodeling to execute mitophagy

Journal Article · 2020 Mitochondrial failure caused by Parkin mutations contributes to Parkinson’s disease. Parkin binds, ubiquitinates, and targets impaired mitochondria for autophagic destruction. Robust mitophagy involves peri-nuclear concentration of Parkin-tagged mitochondr ... Full text Cite

A method to culture human alveolar rhabdomyosarcoma cell lines as rhabdospheres demonstrates an enrichment in stemness and notch signaling.

Journal Article Biol Open · January 1, 2020 The development of three-dimensional cell culture techniques has allowed cancer researchers to study the stemness properties of cancer cells in in vitro culture. However, a method to grow PAX3-FOXO1 fusion-positive rhabdomyosarcoma (FP-RMS) - an aggressive ... Full text Link to item Cite

Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging.

Journal Article PLoS Genet · December 2019 Malaria parasites follow a complex life cycle that consists of multiple stages that span from the human host to the mosquito vector. Among the species causing malaria, Plasmodium falciparum is the most lethal, with clinical symptoms manifesting during the ... Full text Open Access Link to item Cite

The Hippo Pathway Effector TAZ Regulates Ferroptosis in Renal Cell Carcinoma.

Journal Article Cell Rep · September 3, 2019 Despite recent advances, the poor outcomes in renal cell carcinoma (RCC) suggest novel therapeutics are needed. Ferroptosis is a form of regulated cell death, which may have therapeutic potential toward RCC; however, much remains unknown about the determin ... Full text Link to item Cite

Abstract 3590: Mechanisms and inhibition RIOK2 for obesity-driven prostate cancer

Conference Cancer Research · July 1, 2019 AbstractObesity is associated with greater risk of high-grade prostate cancer (PC), recurrence after therapy, metastases, and PC specific mortality. The fact that obesity is a PC risk factor creates an oppor ... Full text Cite

Abstract 4900: Dynamic metabolic response of prostate cancer patients treated with ADT and low carb diet

Conference Cancer Research · July 1, 2019 AbstractBackground: Prostate cancer (PrCa) is one of the most common cancers among men and managed through surgery, hormonal therapy, chemotherapy, radiation, and cryotherapy. Depending on the stage of PrCa, ... Full text Cite

Abstract 2667: Genetic removal of metazoan SpoT homolog I (MESH1) inhibits proliferation through the repression of HIPPO effector TAZ

Conference Cancer Research · July 1, 2019 AbstractThe capacity of tumor cells to survive various stresses is an essential property that endows them invulnerability. One of the bacterial key adaptive strategies against nutrient deprivation is stringe ... Full text Cite

Abstract 4472: The hippo pathway effector TAZ regulates ferroptosis in renal cell carcinoma

Conference Cancer Research · July 1, 2019 AbstractFerroptosis is a newly appreciated lipid peroxidation-dependent regulated cell death with relevance for many human diseases, which may be a tumor suppression mechanism and may have antitumor potentia ... Full text Cite

Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells and protects against liver fibrosis

Conference · 2019 Background and Aims Liver fibrosis develops in the context of excessive oxidative stress, cell death and accumulation of myofibroblasts (MFs) derived from hepatic stellate cells (HSCs). Ferroptosis is a type of regulated cell death that can be cau ... Full text Cite

Quantitative phase imaging of erythrocytes under microfluidic constriction in a high refractive index medium reveals water content changes.

Journal Article Microsyst Nanoeng · 2019 Changes in the deformability of red blood cells can reveal a range of pathologies. For example, cells which have been stored for transfusion are known to exhibit progressively impaired deformability. Thus, this aspect of red blood cells has been characteri ... Full text Open Access Link to item Cite

RIPK3 upregulation confers robust proliferation and collateral cystine-dependence on breast cancer recurrence

Journal Article · 2019 The molecular and genetic basis of tumor recurrence is complex and poorly understood. RIPK3 is a key effector in programmed necrotic cell death and, therefore, its expression is frequently suppressed in primary tumors. In a transcriptome profiling between ... Full text Cite

Glycosylation of gigaxonin regulates intermediate filaments: Novel molecular insights into giant axonal neuropathy

Journal Article · 2019 Gigaxonin (also known as KLHL16) is an E3 ligase adaptor protein that promotes the ubiquitination and degradation of intermediate filament (IF) proteins. Mutations in human gigaxonin cause the fatal neurodegenerative disease giant axonal neuropathy (GAN), ... Full text Open Access Cite

Functional crosstalk among oxidative stress and O-GlcNAc signaling pathways.

Journal Article Glycobiology · August 1, 2018 In metazoans, thousands of intracellular proteins are modified with O-linked β-N-acetylglucosamine (O-GlcNAc) in response to a wide range of stimuli and stresses. In particular, a complex and evolutionarily conserved interplay between O-GlcNAcylation and o ... Full text Open Access Link to item Cite

Methods for high-dimensional analysis of cells dissociated from cryopreserved synovial tissue.

Journal Article Arthritis Res Ther · July 11, 2018 BACKGROUND: Detailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct ... Full text Link to item Cite

Single-Cell Analysis Reveals Distinct Gene Expression and Heterogeneity in Male and Female Plasmodium falciparum Gametocytes.

Journal Article mSphere · April 25, 2018 Sexual reproduction is an obligate step in the Plasmodium falciparum life cycle, with mature gametocytes being the only form of the parasite capable of human-to-mosquito transmission. Development of male and female gametocytes takes 9 to 12 days, and altho ... Full text Open Access Link to item Cite

CoA synthase regulates mitotic fidelity via CBP-mediated acetylation.

Conference Nat Commun · March 12, 2018 The temporal activation of kinases and timely ubiquitin-mediated degradation is central to faithful mitosis. Here we present evidence that acetylation controlled by Coenzyme A synthase (COASY) and acetyltransferase CBP constitutes a novel mechanism that en ... Full text Open Access Link to item Cite

Heterogeneous timing of asexual cycles in Plasmodium falciparum quantified by extended time-lapse microscopy

Journal Article · 2018 ABSTRACT Malarial fever arises from the synchronous bursting of human red blood cells by the Plasmodium parasite. The released parasites re-infect neighboring red blood cells and undergo another asexual cycle of differentiation and proliferation f ... Full text Cite

Mammalian stringent-like response mediated by the cytosolic NADPH phosphatase MESH1

Journal Article · 2018 Nutrient deprivation triggers stringent response in bacteria, allowing rapid reallocation of resources from proliferation toward stress survival. Critical to this process is the accumulation/degradation of (p)ppGpp regulated by the RelA/SpoT homologues. Wh ... Full text Cite

Contextual tumor suppressor function of T cell death-associated gene 8 (TDAG8) in hematological malignancies.

Journal Article J Transl Med · October 10, 2017 BACKGROUND: Extracellular acidosis is a condition found within the tumor microenvironment due to inadequate blood perfusion, hypoxia, and altered tumor cell metabolism. Acidosis has pleiotropic effects on malignant progression; therefore it is essential to ... Full text Link to item Cite

Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer.

Journal Article Radiat Res · August 2017 Breast cancer is the most common malignancy diagnosed among women and represents a heterogeneous group of subtypes. Radiation therapy is a critical component of treatment for breast cancer patients. However, little is known about radiation response among t ... Full text Link to item Cite

Glycosylation of KEAP1 links nutrient sensing to redox stress signaling.

Journal Article EMBO J · August 1, 2017 O-GlcNAcylation is an essential, nutrient-sensitive post-translational modification, but its biochemical and phenotypic effects remain incompletely understood. To address this question, we investigated the global transcriptional response to perturbations i ... Full text Open Access Link to item Cite

Cystine addiction of triple-negative breast cancer associated with EMT augmented death signaling.

Journal Article Oncogene · July 27, 2017 Despite the advances in the diagnosis and treatment of breast cancer, breast cancers still cause significant mortality. For some patients, especially those with triple-negative breast cancer, current treatments continue to be limited and ineffective. There ... Full text Link to item Cite

Cystine addiction of triple-negative breast cancer associated with EMT augmented death signaling.

Journal Article Oncogene · July 27, 2017 This corrects the article DOI: 10.1038/onc.2016.394. ... Full text Link to item Cite

Abstract 5457: OGT restrains the NRF2 antioxidant pathway via O-GlcNAcylation of KEAP1

Conference Cancer Research · July 1, 2017 AbstractO-GlcNAcylation is a reversible post-translational modification that adds an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety onto serine/threonine residues of target proteins. This modification is r ... Full text Cite

Trans-kingdom small RNA transfer during host-pathogen interactions: The case of P. falciparum and erythrocytes.

Journal Article RNA Biol · April 3, 2017 This review focuses on the role of trans-kingdom movement of small RNA (sRNA) molecules between parasites, particularly Plasmodium falciparum, and their respective host cells. While the intercellular transfer of sRNAs within organisms is well recognized, r ... Full text Link to item Cite

CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer.

Journal Article Cancer Res · April 1, 2017 In this study, we used a bioinformatic approach to identify genes whose expression is dysregulated in human prostate cancers. One of the most dramatically downregulated genes identified encodes CYP27A1, an enzyme involved in regulating cellular cholesterol ... Full text Link to item Cite

Discovery, Genomic Analysis, and Functional Role of the Erythrocyte RNAs

Journal Article Current Pathobiology Reports · March 1, 2017 Purpose of Review: Human erythrocytes are responsible for oxygen delivery in the body. Erythrocytes are a product of terminal differentiated erythroid cells that accumulate hemoglobin and exclude nuclei. The long-held conventional wisdom has been that matu ... Full text Cite

KEAP1 has a sweet spot: A new connection between intracellular glycosylation and redox stress signaling in cancer cells.

Journal Article Mol Cell Oncol · 2017 The KEAP1/NRF2 pathway is a master regulator of the redox stress response and is dysregulated in numerous human tumors. We discovered that NRF2 signaling is controlled by the site-specific glycosylation of KEAP1, revealing a potentially broad link among nu ... Full text Open Access Link to item Cite

Fluorescence-based measurement of cystine uptake through xCT shows requirement for ROS detoxification in activated lymphocytes.

Journal Article J Immunol Methods · November 2016 T and B lymphocytes undergo metabolic re-programming upon activation that is essential to allow bioenergetics, cell survival, and intermediates for cell proliferation and function. To support changes in the activity of signaling pathways and to provide suf ... Full text Link to item Cite

Discovery of Manassantin A Protein Targets Using Large-Scale Protein Folding and Stability Measurements.

Journal Article J Proteome Res · August 5, 2016 Manassantin A is a natural product that has been shown to have anticancer activity in cell-based assays, but has a largely unknown mode-of-action. Described here is the use of two different energetics-based approaches to identify protein targets of manassa ... Full text Link to item Cite

Abstract 1647: Radiation response genome-wide analysis using paired pre and post-radiation FFPE human breast tumor samples

Conference Cancer Research · July 15, 2016 AbstractBackground: Breast cancer is the most common female malignancy in the US, and radiotherapy is a routine part of multi-disciplinary breast cancer care. Radiation treatment (RT) tailored to target radi ... Full text Cite

Abstract 1628: MAFF, a new hypoxia target gene involving tumor invasion and metastasis

Conference Cancer Research · July 15, 2016 AbstractActivation of hypoxia-inducible factor (HIF) under hypoxia is significantly correlated with tumor progression and treatment resistance by regulating target genes involved in invasion, metastasis, ang ... Full text Cite

GNA13 loss in germinal center B cells leads to impaired apoptosis and promotes lymphoma in vivo.

Journal Article Blood · June 2, 2016 GNA13 is the most frequently mutated gene in germinal center (GC)-derived B-cell lymphomas, including nearly a quarter of Burkitt lymphoma and GC-derived diffuse large B-cell lymphoma. These mutations occur in a pattern consistent with loss of function. We ... Full text Link to item Cite

Hemoglobin consumption by P. falciparum in individual erythrocytes imaged via quantitative phase spectroscopy.

Journal Article Sci Rep · April 18, 2016 Plasmodium falciparum infection causes structural and biochemical changes in red blood cells (RBCs). To quantify these changes, we apply a novel optical technique, quantitative phase spectroscopy (QPS) to characterize individual red blood cells (RBCs) duri ... Full text Link to item Cite

Cystine Deprivation Triggers Programmed Necrosis in VHL-Deficient Renal Cell Carcinomas.

Journal Article Cancer Res · April 1, 2016 Oncogenic transformation may reprogram tumor metabolism and render cancer cells addicted to extracellular nutrients. Deprivation of these nutrients may therefore represent a therapeutic opportunity, but predicting which nutrients cancer cells become addict ... Full text Link to item Cite

Nrf2 is the key to chemotherapy resistance in MCF7 breast cancer cells under hypoxia.

Journal Article Oncotarget · March 22, 2016 Hypoxia leads to reactive oxygen species (ROS) imbalance, which is proposed to associate with drug resistance and oncogenesis. Inhibition of enzymes of antioxidant balancing system in tumor cells was shown to reduce chemoresistance under hypoxia. However, ... Full text Link to item Cite

Phase 1 Study of a Sulforaphane-Containing Broccoli Sprout Homogenate for Sickle Cell Disease.

Journal Article PLoS One · 2016 Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide. Our previous results indicate that the reduced oxidative stress capacity of sickle erythrocytes may be caused by decreased expression of NRF2 (Nuclear factor (erythroid-deri ... Full text Link to item Cite

Automated Detection of P. falciparum Using Machine Learning Algorithms with Quantitative Phase Images of Unstained Cells.

Journal Article PLoS One · 2016 Malaria detection through microscopic examination of stained blood smears is a diagnostic challenge that heavily relies on the expertise of trained microscopists. This paper presents an automated analysis method for detection and staging of red blood cells ... Full text Open Access Link to item Cite

Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum.

Journal Article J Vis Exp · December 4, 2015 The genetic variation responsible for the sickle cell allele (HbS) enables erythrocytes to resist infection by the malaria parasite, P. falciparum. The molecular basis of this resistance, which is known to be multifactorial, remains incompletely understood ... Full text Link to item Cite

A comprehensive joint analysis of the long and short RNA transcriptomes of human erythrocytes.

Journal Article BMC Genomics · November 16, 2015 BACKGROUND: Human erythrocytes are terminally differentiated, anucleate cells long thought to lack RNAs. However, previous studies have shown the persistence of many small-sized RNAs in erythrocytes. To comprehensively define the erythrocyte transcriptome, ... Full text Link to item Cite

Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3-FOXO1-Positive Alveolar Rhabdomyosarcoma.

Journal Article Clin Cancer Res · November 1, 2015 PURPOSE: Rhabdomyosarcoma (RMS) is a soft tissue sarcoma associated with the skeletal muscle lineage. Of the two predominant subtypes, known as embryonal (eRMS) and alveolar (aRMS), aRMS has the poorer prognosis, with a five-year survival rate of <50%. The ... Full text Link to item Cite

FAS Death Receptor: A Breast Cancer Subtype-Specific Radiation Response Biomarker and Potential Therapeutic Target.

Journal Article Radiat Res · November 2015 Although a standardized approach to radiotherapy has been used to treat breast cancer, regardless of subtype (e.g., luminal, basal), recent clinical data suggest that radiation response may vary significantly among subtypes. We hypothesized that this clini ... Full text Link to item Cite

Synthesis and Biological Evaluation of Manassantin Analogues for Hypoxia-Inducible Factor 1α Inhibition.

Journal Article J Med Chem · October 8, 2015 To cope with hypoxia, tumor cells have developed a number of adaptive mechanisms mediated by hypoxia-inducible factor 1 (HIF-1) to promote angiogenesis and cell survival. Due to significant roles of HIF-1 in the initiation, progression, metastasis, and res ... Full text Link to item Cite

ACLY and ACC1 Regulate Hypoxia-Induced Apoptosis by Modulating ETV4 via α-ketoglutarate.

Journal Article PLoS Genet · October 2015 In order to propagate a solid tumor, cancer cells must adapt to and survive under various tumor microenvironment (TME) stresses, such as hypoxia or lactic acidosis. To systematically identify genes that modulate cancer cell survival under stresses, we perf ... Full text Open Access Link to item Cite

A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models.

Journal Article Nat Commun · August 4, 2015 Packaging clinically relevant hydrophobic drugs into a self-assembled nanoparticle can improve their aqueous solubility, plasma half-life, tumour-specific uptake and therapeutic potential. To this end, here we conjugated paclitaxel (PTX) to recombinant chi ... Full text Link to item Cite

Abstract 3331: Gene expression profiling after radiation in human breast cancer specimens and breast cancer cell lines

Conference Cancer Research · August 1, 2015 AbstractBackground: Breast radiotherapy is currently “one size fits all” regardless of breast cancer subtype (eg. luminal, basal). Emerging clinical data suggests that these distinct subtypes of breast cance ... Full text Cite

Abstract 1100: Functional genomics to investigate the genetic determinants of cell death induced by oxidative stresses

Conference Cancer Research · August 1, 2015 AbstractIncreased oxidative stress in the tumor microenvironments is a prominent stress that many tumor cells need to cope with during oncogenesis. The stress depletes intracellular glutathione, increases re ... Full text Cite

Abstract 3004: Contextual RNAi screen identifies ACLY and ACC1 as mediators of hypoxia-induced apoptosis through metabolic and transcriptional mechanisms

Conference Cancer Research · August 1, 2015 AbstractTo become established as a solid tumor, cancer cells must adapt to and survive under various tumor microenvironment (TME) stresses, such as hypoxia or lactic acidosis. While many stress-signaling mec ... Full text Cite

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers.

Journal Article Int J Radiat Oncol Biol Phys · July 15, 2015 PURPOSE: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for ... Full text Link to item Cite

Suppression of PGC-1α Is Critical for Reprogramming Oxidative Metabolism in Renal Cell Carcinoma.

Journal Article Cell Rep · July 7, 2015 Long believed to be a byproduct of malignant transformation, reprogramming of cellular metabolism is now recognized as a driving force in tumorigenesis. In clear cell renal cell carcinoma (ccRCC), frequent activation of HIF signaling induces a metabolic sw ... Full text Link to item Cite

Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism.

Journal Article Thromb Res · April 2015 INTRODUCTION: Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose pa ... Full text Link to item Cite

Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis.

Journal Article PLoS Genet · April 2015 Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger ... Full text Link to item Cite

Design, synthesis, and biological evaluation of manassantin analogues for HIF-1 alpha inhibition

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 22, 2015 Link to item Cite

Syngeneic Murine Ovarian Cancer Model Reveals That Ascites Enriches for Ovarian Cancer Stem-Like Cells Expressing Membrane GRP78.

Journal Article Mol Cancer Ther · March 2015 Patients with ovarian cancer are generally diagnosed at FIGO (International Federation of Gynecology and Obstetrics) stage III/IV, when ascites is common. The volume of ascites correlates positively with the extent of metastasis and negatively with prognos ... Full text Link to item Cite

E2F1-Mediated Induction of NFYB Attenuates Apoptosis via Joint Regulation of a Pro-Survival Transcriptional Program.

Journal Article PLoS One · 2015 The E2F1 transcription factor regulates cell proliferation and apoptosis through the control of a considerable variety of target genes. Previous work has detailed the role of other transcription factors in mediating the specificity of E2F function. Here we ... Full text Link to item Cite

Modulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis.

Journal Article PLoS One · 2015 PICALM (Phosphatidyl Inositol Clathrin Assembly Lymphoid Myeloid protein) is a ubiquitously expressed protein that plays a role in clathrin-mediated endocytosis. PICALM also affects the internalization and trafficking of SNAREs and modulates macroautophagy ... Full text Link to item Cite

Abstract PR09: A genome-wide RNAi screen reveals a protective role of decreased lipogenesis under hypoxia

Conference Cancer Research · January 1, 2015 AbstractAs solid tumors form, a number of physiological changes occur within the tumor, including low oxygen levels (hypoxia) and an accumulation of lactic acid with concomitant lowered pH levels (lactic aci ... Full text Cite

Alternative fuels for cancer cells.

Journal Article Cancer J · 2015 Tumor metabolism is significantly altered to support the various metabolic needs of tumor cells. The most prominent change is the increased tumor glycolysis that leads to increased glucose uptake and utilization. However, it has become obvious that many no ... Full text Link to item Cite

The role of glutamine synthetase in the glutamine independence in mammary tissue

Journal Article · January 1, 2015 Glutamine addiction of cancer cells is thought to be an attractive way to prevent cancer growth and spreading. Although some regulatory factors of glutamine consumption are known, the actual cell-type specific regulatory mechanism hasn’t been explored yet. ... Full text Cite

Utilization of the Eμ-Myc mouse to model heterogeneity of therapeutic response.

Journal Article Mol Cancer Ther · December 2014 Human aggressive B-cell non-Hodgkin lymphomas (NHL) encompass the continuum between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL), and display considerable clinical and biologic heterogeneity, most notably related to therapy response. We previ ... Full text Link to item Cite

An unexpected alliance between stress responses to drive oncogenesis.

Journal Article Breast Cancer Res · November 6, 2014 XBP1 is a well-characterized regulator of the unfolding protein response that is activated in response to unfolded or misfolded proteins or nutrient deprivation. The conventional wisdom is that XBP1 is activated to coordinate the unfolded protein response ... Full text Link to item Cite

Glycolysis-dependent histone deacetylase 4 degradation regulates inflammatory cytokine production.

Journal Article Mol Biol Cell · November 1, 2014 Activation of the inflammatory response is accompanied by a metabolic shift to aerobic glycolysis. Here we identify histone deacetylase 4 (HDAC4) as a new component of the immunometabolic program. We show that HDAC4 is required for efficient inflammatory c ... Full text Link to item Cite

Abstract A57: The secreted Wnt inhibitor SFRP3 is required for PAX3-FOXO1-positive alveolar rhabdomyosarcoma tumorigenesis

Conference Cancer Research · October 15, 2014 AbstractIntroduction: This study aims to understand the contribution of the Wnt pathway inhibitor secreted frizzled related protein 3 (SFRP3) to alveolar rhabdomyosarcoma tumorigenesis. Rhabdomyosarcoma is t ... Full text Cite

Preoperative Partial Breast Radiation Therapy: One Year Outcomes and Radiation-Induced Changes in Gene Expression

Conference International Journal of Radiation Oncology*Biology*Physics · September 2014 Full text Cite

A joint analysis of metabolomics and genetics of breast cancer.

Journal Article Breast Cancer Res · August 5, 2014 INTRODUCTION: Remodeling of cellular metabolism appears to be a consequence and possibly a cause of oncogenic transformation in human cancers. Specific aspects of altered tumor metabolism may be amenable to therapeutic intervention and could be coordinated ... Full text Link to item Cite

Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression.

Journal Article J Clin Invest · January 2014 Alveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle characterized by expression of the paired box 3-forkhead box protein O1 (PAX3-FOXO1) fusion oncogene. Despite its discovery nearly two decades ago, the mechanisms by which PAX3-FO ... Full text Link to item Cite

A genomic analysis of cellular responses and adaptions to extracellular acidosis

Chapter · January 1, 2014 Even though lactic acidosis is a prominent feature of solid tumors, we have limited understanding of the mechanisms by which lactic acidosis influences the genetic, epigenetic, proteomic, and metabolic phenotypes of cancer cells. This chapter aims to (1) b ... Full text Cite

Molecular genetics of dysregulated pH homeostasis

Book · January 1, 2014 Most biological reactions and functions occur within a narrow range of pH. Any changes in the pH have great impacts on the biological function at every level, including protein folding, enzymatic activities and proliferation, and cell death. Therefore, mai ... Full text Cite

Introduction: Molecular genetics of acid sensing and response

Chapter · January 1, 2014 Since most biological reactions in human body occur within narrow ranges around neutral environments, any changes in the pH environment have great impacts on a wide variety of functions, including gene expression, protein folding, enzymatic activities, cel ... Full text Cite

Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress.

Journal Article Cancer Metab · December 23, 2013 BACKGROUND: A variety of oncogenic and environmental factors alter tumor metabolism to serve the distinct cellular biosynthetic and bioenergetic needs present during oncogenesis. Extracellular acidosis is a common microenvironmental stress in solid tumors, ... Full text Link to item Cite

Fish oil slows prostate cancer xenograft growth relative to other dietary fats and is associated with decreased mitochondrial and insulin pathway gene expression

Journal Article Prostate Cancer and Prostatic Diseases · December 1, 2013 BACKGROUND:Previous mouse studies suggest that decreasing dietary fat content can slow prostate cancer (PCa) growth. To our knowledge, no study has yet compared the effect of multiple different fats on PCa progression. We sought to systematically compare t ... Full text Cite

Fish oil slows prostate cancer xenograft growth relative to other dietary fats and is associated with decreased mitochondrial and insulin pathway gene expression.

Journal Article Prostate Cancer Prostatic Dis · December 2013 BACKGROUND: Previous mouse studies suggest that decreasing dietary fat content can slow prostate cancer (PCa) growth. To our knowledge, no study has yet compared the effect of multiple different fats on PCa progression. We sought to systematically compare ... Full text Link to item Cite

Aspirin exposure reveals novel genes associated with platelet function and cardiovascular events.

Journal Article J Am Coll Cardiol · October 1, 2013 OBJECTIVES: The aim of this study was to develop ribonucleic acid (RNA) profiles that could serve as novel biomarkers for the response to aspirin. BACKGROUND: Aspirin reduces death and myocardial infarction (MI), suggesting that aspirin interacts with biol ... Full text Link to item Cite

Understanding the tumor microenvironment and radioresistance by combining functional imaging with global gene expression.

Journal Article Semin Radiat Oncol · October 2013 The objective of this review is to present an argument for performing joint analyses between functional imaging with global gene expression studies. The reason for making this link is that tumor microenvironmental influences on functional imaging can be un ... Full text Link to item Cite

Abstract A18: Genetic elements of cancer cell survival in tumor microenvironment stresses

Journal Article Molecular Cancer Therapeutics · May 1, 2013 AbstractAs solid human cancer tumors form there are a number of physiological changes that occur within the tumor itself, including low oxygen levels (hypoxia) and an accumulation of lactic acid with concomi ... Full text Cite

Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin.

Journal Article PLoS Genet · April 2013 Ferroportin (FPN) is the only known cellular iron exporter in mammalian cells and plays a critical role in the maintenance of both cellular and systemic iron balance. During iron deprivation, the translation of FPN is repressed by iron regulatory proteins ... Full text Link to item Cite

Acidosis activation of the proton-sensing GPR4 receptor stimulates vascular endothelial cell inflammatory responses revealed by transcriptome analysis.

Journal Article PLoS One · 2013 Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular m ... Full text Link to item Cite

Catabolism of exogenous lactate reveals it as a legitimate metabolic substrate in breast cancer.

Journal Article PLoS One · 2013 Lactate accumulation in tumors has been associated with metastases and poor overall survival in cancer patients. Lactate promotes angiogenesis and metastasis, providing rationale for understanding how it is processed by cells. The concentration of lactate ... Full text Link to item Cite

A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation.

Journal Article Genome Res · December 2012 Monoallelic point mutations of the NADP(+)-dependent isocitrate dehydrogenases IDH1 and IDH2 occur frequently in gliomas, acute myeloid leukemias, and chondromas, and display robust association with specific DNA hypermethylation signatures. Here we show th ... Full text Link to item Cite

Using High-Throughput Sequencing of Red Blood Cells and Platelets to Identify Micrornas Associated with Hematopoiesis.

Conference Blood · November 16, 2012 AbstractAbstract 2326Human mature red blood cells (RBC) and platelets are both terminally differentiated cells lacking nuclei. However, these two cell types do possess a dive ... Full text Cite

Gene Expression Response to Ionizing Radiation in Luminal and Basal Breast Cancer Cell Lines

Conference International Journal of Radiation Oncology*Biology*Physics · November 2012 Full text Cite

Global identification of MLL2-targeted loci reveals MLL2's role in diverse signaling pathways.

Journal Article Proc Natl Acad Sci U S A · October 23, 2012 Myeloid/lymphoid or mixed-lineage leukemia (MLL)-family genes encode histone lysine methyltransferases that play important roles in epigenetic regulation of gene transcription. MLL genes are frequently mutated in human cancers. Unlike MLL1, MLL2 (also know ... Full text Link to item Cite

Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance.

Journal Article Cell Host Microbe · August 16, 2012 Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains ... Full text Link to item Cite

Abstract 5255: Methionine restriction limits prostate tumor cell proliferation

Conference Cancer Research · April 15, 2012 AbstractIntroduction: Methionine restriction has been shown to have growth inhibitory effects in a number of tumor cell lines in vitro. Methionine restriction has previously been demonstrated to slow PC-3 pr ... Full text Cite

Time-dependent changes in non-COX-1-dependent platelet function with daily aspirin therapy.

Journal Article J Thromb Thrombolysis · April 2012 To develop an integrated metric of non-COX-1-dependent platelet function (NCDPF) to measure the temporal response to aspirin in healthy volunteers and diabetics. NCDPF on aspirin demonstrates wide variability, despite suppression of COX-1. Although a varie ... Full text Link to item Cite

Functional interaction between responses to lactic acidosis and hypoxia regulates genomic transcriptional outputs.

Journal Article Cancer Res · January 15, 2012 Within solid tumor microenvironments, lactic acidosis, and hypoxia each have powerful effects on cancer pathophysiology. However, the influence that these processes exert on each other is unknown. Here, we report that a significant portion of the transcrip ... Full text Link to item Cite

Associations between Intake of Folate, Methionine, and Vitamins B-12, B-6 and Prostate Cancer Risk in American Veterans.

Journal Article J Cancer Epidemiol · 2012 Prostate cancer (PC) is the second leading cause of cancer death in men. Recent reports suggest that excess of nutrients involved in the one-carbon metabolism pathway increases PC risk; however, empirical data are lacking. Veteran American men (272 control ... Full text Open Access Link to item Cite

Whole blood gene expression analyses in patients with single versus recurrent venous thromboembolism.

Journal Article Thromb Res · December 2011 INTRODUCTION: Venous thromboembolism may recur in up to 30% of patients with a spontaneous venous thromboembolism after a standard course of anticoagulation. Identification of patients at risk for recurrent venous thromboembolism would facilitate decisions ... Full text Link to item Cite

Protein Pathway Activation after Ionizing Radiation in Luminal and Basal Breast Cancer Cell Lines

Journal Article International Journal of Radiation Oncology*Biology*Physics · October 2011 Full text Cite

Polysome profiling of the malaria parasite Plasmodium falciparum.

Journal Article Mol Biochem Parasitol · September 2011 In the malaria parasite Plasmodium falciparum, global studies of translational regulation have been hampered by the inability to isolate malaria polysomes. We describe here a novel method for polysome profiling in P. falciparum, a powerful approach which a ... Full text Link to item Cite

Targeting GLUT1 and the Warburg effect in renal cell carcinoma by chemical synthetic lethality.

Journal Article Sci Transl Med · August 3, 2011 Identifying new targeted therapies that kill tumor cells while sparing normal tissue is a major challenge of cancer research. Using a high-throughput chemical synthetic lethal screen, we sought to identify compounds that exploit the loss of the von Hippel- ... Full text Link to item Cite

Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia.

Journal Article PLoS Genet · August 2011 Although significant variations in the metabolic profiles exist among different cells, little is understood in terms of genetic regulations of such cell type-specific metabolic phenotypes and nutrient requirements. While many cancer cells depend on exogeno ... Full text Link to item Cite

Glomeruloid microvascular proliferation is associated with lack of response to chemotherapy in breast cancer.

Journal Article Br J Cancer · June 28, 2011 BACKGROUND: Glomeruloid microvascular proliferation (GMP), a novel histology-based angiogenesis marker, has been associated with decreased survival in several human cancers. METHODS: In this study, we evaluated the ability of GMP to predict clinical respon ... Full text Link to item Cite

Analysis of tumor environmental response and oncogenic pathway activation identifies distinct basal and luminal features in HER2-related breast tumor subtypes.

Journal Article Breast Cancer Res · June 7, 2011 INTRODUCTION: Breast cancer heterogeneity occurs as a consequence of the dysregulation of numerous oncogenic pathways as well as many non-genetic factors, including tumor microenvironmental stresses such as hypoxia, lactic acidosis, and glucose deprivation ... Full text Link to item Cite

Abstract 1518: Gene expression profiling reveals acidosis/GPR4-induced inflammatory responses in vascular endothelial cells

Conference Cancer Research · April 15, 2011 AbstractDue to deficient blood perfusion, hypoxia, and glycolytic metabolism, acidic tissue microenvironments commonly exist in solid tumors, inflammation, and many other pathological conditions. However, th ... Full text Cite

Comparison of genomics and functional imaging from canine sarcomas treated with thermoradiotherapy predicts therapeutic response and identifies combination therapeutics.

Journal Article Clin Cancer Res · April 15, 2011 PURPOSE: While hyperthermia is an effective adjuvant treatment to radiotherapy, we do not completely understand the nature of the response heterogeneity. EXPERIMENTAL DESIGN: We performed gene expression analysis of 22 spontaneous canine sarcomas before an ... Full text Link to item Cite

microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease.

Journal Article Blood · November 18, 2010 Although individuals with homozygous sickle cell disease (HbSS) share the same genetic mutation, the severity and manifestations of this disease are extremely heterogeneous. We have previously shown that the microRNA expression in normal and HbSS erythrocy ... Full text Link to item Cite

Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA.

Journal Article PLoS Genet · September 2, 2010 Although lactic acidosis is a prominent feature of solid tumors, we still have limited understanding of the mechanisms by which lactic acidosis influences metabolic phenotypes of cancer cells. We compared global transcriptional responses of breast cancer c ... Full text Open Access Link to item Cite

Latent factor analysis to discover pathway-associated putative segmental aneuploidies in human cancers.

Journal Article PLoS Comput Biol · September 2, 2010 Tumor microenvironmental stresses, such as hypoxia and lactic acidosis, play important roles in tumor progression. Although gene signatures reflecting the influence of these stresses are powerful approaches to link expression with phenotypes, they do not f ... Full text Open Access Link to item Cite

Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells.

Journal Article Nat Med · April 2010 Hematopoietic stem cell (HSC) self-renewal is regulated by both intrinsic and extrinsic signals. Although some of the pathways that regulate HSC self-renewal have been uncovered, it remains largely unknown whether these pathways can be triggered by deliver ... Full text Link to item Cite

Contact lens management of infantile aphakia.

Journal Article Clin Exp Optom · January 2010 The visual outcomes for infants 18 months or younger with cataracts have improved dramatically over the past couple of decades. Earlier detection of infantile cataract and prompt surgical removal-with subsequent visual rehabilitation with contact lenses-me ... Full text Link to item Cite

Isolation and characterization of microRNAs of human mature erythrocytes.

Journal Article Methods Mol Biol · 2010 Human mature erythrocytes are terminally differentiated cells that have lost their nuclei and organelles during development. Even though mature erythrocytes lack ribosomal and other large-sized RNAs, they still retain small-sized RNAs. We have recently sho ... Full text Link to item Cite

p38gamma mitogen-activated protein kinase is a key regulator in skeletal muscle metabolic adaptation in mice.

Journal Article PLoS One · November 20, 2009 Regular endurance exercise induces skeletal muscle contractile and metabolic adaptations, conferring salutary health benefits, such as protection against the metabolic syndrome. The plasticity of skeletal muscle has been extensively investigated, but how t ... Full text Link to item Cite

Tumor vasculature is regulated by PHD2-mediated angiogenesis and bone marrow-derived cell recruitment.

Journal Article Cancer Cell · June 2, 2009 Sustained angiogenesis, through either local sprouting (angiogenesis) or the recruitment of bone marrow-derived cells (BMDCs) (vasculogenesis), is essential to the development of a tumor. How BMDCs are recruited to the tumor and their contribution to the t ... Full text Link to item Cite

Cross-study projections of genomic biomarkers: An evaluation in cancer genomics

Journal Article Plos One · February 19, 2009 Human disease studies using DNA microarrays in both clinical/ observational and experimental/controlled studies are having increasing impact on our understanding of the complexity of human diseases. A fundamental concept is the use of gene expression as a ... Full text Cite

Cross-study projections of genomic biomarkers: an evaluation in cancer genomics.

Journal Article PLoS One · 2009 Human disease studies using DNA microarrays in both clinical/observational and experimental/controlled studies are having increasing impact on our understanding of the complexity of human diseases. A fundamental concept is the use of gene expression as a " ... Full text Link to item Cite

AN INTEGRATIVE ANALYSIS OF CANCER GENE EXPRESSION STUDIES USING BAYESIAN LATENT FACTOR MODELING.

Journal Article Ann Appl Stat · 2009 We present an applied study in cancer genomics for integrating data and inferences from laboratory experiments on cancer cell lines with observational data obtained from human breast cancer studies. The biological focus is on improving understanding of tra ... Full text Link to item Cite

The genomic analysis of lactic acidosis and acidosis response in human cancers.

Journal Article PLoS Genet · December 2008 The tumor microenvironment has a significant impact on tumor development. Two important determinants in this environment are hypoxia and lactic acidosis. Although lactic acidosis has long been recognized as an important factor in cancer, relatively little ... Full text Link to item Cite

Combining biological gene expression signatures in predicting outcome in breast cancer: An alternative to supervised classification.

Journal Article Eur J Cancer · October 2008 INTRODUCTION: Gene expression profiling has been extensively used to predict outcome in breast cancer patients. We have previously reported on biological hypothesis-driven analysis of gene expression profiling data and we wished to extend this approach thr ... Full text Link to item Cite

The genomic analysis of erythrocyte microRNA expression in sickle cell diseases.

Journal Article PLoS One · June 4, 2008 BACKGROUND: Since mature erythrocytes are terminally differentiated cells without nuclei and organelles, it is commonly thought that they do not contain nucleic acids. In this study, we have re-examined this issue by analyzing the transcriptome of a purifi ... Full text Open Access Link to item Cite

Transcriptome analysis

Journal Article · March 26, 2008 Full text Cite

Modeling cancer progression via pathway dependencies.

Journal Article PLoS Comput Biol · February 2008 Cancer is a heterogeneous disease often requiring a complexity of alterations to drive a normal cell to a malignancy and ultimately to a metastatic state. Certain genetic perturbations have been implicated for initiation and progression. However, to a grea ... Full text Link to item Cite

A viral microRNA functions as an orthologue of cellular miR-155.

Journal Article Nature · December 13, 2007 All metazoan eukaryotes express microRNAs (miRNAs), roughly 22-nucleotide regulatory RNAs that can repress the expression of messenger RNAs bearing complementary sequences. Several DNA viruses also express miRNAs in infected cells, suggesting a role in vir ... Full text Link to item Cite

Regional specialization of endothelial cells as revealed by genomic analysis

Journal Article · December 1, 2007 The vascular system is locally specialized to accommodate widely varying needs of individual tissues. The regional specialization of vascular structure is closely linked to the topographic differentiation of endothelial cells (ECs). The gene expression pro ... Full text Cite

The Identification and Genomic Analysis of microRNAs in Human Erythrocytes in Sickle Cell Diseases.

Conference Blood · November 16, 2007 AbstractErythrocytes are circulating blood cells responsible for efficient gas exchange in human body. Since mature erythrocytes are terminally differentiated cells without nuclei and organelles, it is commo ... Full text Cite

Gene expression programs of human smooth muscle cells: tissue-specific differentiation and prognostic significance in breast cancers.

Journal Article PLoS Genet · September 2007 Smooth muscle is present in a wide variety of anatomical locations, such as blood vessels, various visceral organs, and hair follicles. Contraction of smooth muscle is central to functions as diverse as peristalsis, urination, respiration, and the maintena ... Full text Link to item Cite

The potential role of intrinsic hypoxia markers as prognostic variables in cancer.

Journal Article Antioxid Redox Signal · August 2007 Tumor hypoxia is related to tumor progression and therapy resistance, which leads to poor patient outcome. It has been suggested that measuring the hypoxic status of a tumor helps to predict patient outcome and to select more targeted treatment. However, c ... Full text Link to item Cite

Minimizing off-target effects by using diced siRNAs for RNA interference.

Journal Article J RNAi Gene Silencing · July 17, 2006 Microarray studies have shown that individual synthetic small interfering RNAs (siRNAs) can have substantial off-target effects. Pools of siRNAs, produced by incubation of dsRNAs with recombinant Dicer or RNase III, can also be used to silence genes. Here ... Link to item Cite

Lysyl oxidase is essential for hypoxia-induced metastasis.

Journal Article Nature · April 27, 2006 Metastasis is a multistep process responsible for most cancer deaths, and it can be influenced by both the immediate microenvironment (cell-cell or cell-matrix interactions) and the extended tumour microenvironment (for example vascularization). Hypoxia (l ... Full text Link to item Cite

Gene expression programs in response to hypoxia: cell type specificity and prognostic significance in human cancers.

Journal Article PLoS Med · March 2006 BACKGROUND: Inadequate oxygen (hypoxia) triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxia response ... Full text Link to item Cite

Predicting a local recurrence after breast-conserving therapy by gene expression profiling.

Journal Article Breast Cancer Res · 2006 INTRODUCTION: To tailor local treatment in breast cancer patients there is a need for predicting ipsilateral recurrences after breast-conserving therapy. After adequate treatment (excision with free margins and radiotherapy), young age and incompletely exc ... Full text Link to item Cite

High-throughput RNA interference

Journal Article · January 1, 2005 Introduction RNA interference (RNAi) is an evolutionarily conserved pathway of gene silencing that identifies and destroys mRNA sequences derived from selfish repetitive or viral sequences. The mechanisms and physiologic functions of RNAi pathways are disc ... Full text Cite

Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds.

Journal Article PLoS Biol · February 2004 Cancer invasion and metastasis have been likened to wound healing gone awry. Despite parallels in cellular behavior between cancer progression and wound healing, the molecular relationships between these two processes and their prognostic implications are ... Full text Link to item Cite

Systemic and cell type-specific gene expression patterns in scleroderma skin.

Journal Article Proc Natl Acad Sci U S A · October 14, 2003 We used DNA microarrays representing >12,000 human genes to characterize gene expression patterns in skin biopsies from individuals with a diagnosis of systemic sclerosis with diffuse scleroderma. We found consistent differences in the patterns of gene exp ... Full text Link to item Cite

Endothelial cell diversity revealed by global expression profiling.

Journal Article Proc Natl Acad Sci U S A · September 16, 2003 The vascular system is locally specialized to accommodate widely varying blood flow and pressure and the distinct needs of individual tissues. The endothelial cells (ECs) that line the lumens of blood and lymphatic vessels play an integral role in the regi ... Full text Link to item Cite

Genomewide view of gene silencing by small interfering RNAs.

Journal Article Proc Natl Acad Sci U S A · May 27, 2003 RNA interference (RNAi) is an evolutionarily conserved mechanism in plant and animal cells that directs the degradation of messenger RNAs homologous to short double-stranded RNAs termed small interfering RNA (siRNA). The ability of siRNA to direct gene sil ... Full text Link to item Cite

Diversity, topographic differentiation, and positional memory in human fibroblasts.

Journal Article Proc Natl Acad Sci U S A · October 1, 2002 A fundamental feature of the architecture and functional design of vertebrate animals is a stroma, composed of extracellular matrix and mesenchymal cells, which provides a structural scaffold and conduit for blood and lymphatic vessels, nerves, and leukocy ... Full text Link to item Cite

Comprehensive analysis of the gene expression profiles in human gastric cancer cell lines.

Journal Article Oncogene · September 19, 2002 Gastric adenocarcinoma is one of the major malignancies worldwide. Gastric cell lines have been widely used as the model to study the genetics, pharmacology and biochemistry of gastric cancers. Here we describe a comprehensive survey of the gene expression ... Full text Link to item Cite

Differential effect of B lymphocyte-induced maturation protein (Blimp-1) expression on cell fate during B cell development.

Journal Article J Exp Med · August 3, 1998 The B lymphocyte-induced maturation protein (Blimp-1) upregulates the expression of syndecan-1 and J chain and represses that of c-myc. We have transfected Blimp-1 into two sublines of the BCL1 B cell lymphoma that represent distinct stages of B cell devel ... Full text Link to item Cite