Benny Kaipparettu

Baylor College of Medicine | BCM · Department of Molecular & Human Genetics

Bladder cancer (BLCA) mortality is higher in African American (AA) patients compared with European American (EA) patients, but the molecular mechanism underlying race-specific differences are unknown. To address this gap, we conducted comprehensive RNA-Seq, proteomics, and metabolomics analysis of BLCA tumors from AA and EA. Our findings reveal a d...

Background Betulinic acid (BA) has been well investigated for its antiproliferative and mitochondrial pathway-mediated apoptosis-inducing effects on various cancers. However, its poor solubility and off-target activity have limited its utility in clinical trials. Additionally, the immune modulatory role of betulinic acid analogue in the tumor micro...

Bladder cancer mortality is significantly higher in African American patients compared to their European American counterparts. This inferior survival of African American cancer patients is driven at least in part by distinctive intrinsic tumor biology, more specifically altered metabolic activity. However, underlying molecular mechanism for the Af...

The Hispanic (HA) population is the second largest racial/ethnic group in the United States after non-Hispanic White (NHW). Though the HA population usually has a lower reported incidence of cancers compared to NHW, there are racial disparities exist in the mortality rate of some of the cancers. Factors related to the Social Determinants of Health...

Understanding cancer metabolism is crucial for deciphering various cancer hallmarks, including metastasis and immunosuppression. This study investigated the intricate interplay of catabolic processes involving glucose, fatty acids, and glutamine in cancer cells. Recent evidence highlights the dual reliance of cancer cells on glycolysis and oxidativ...

CD24 is a well-characterized breast cancer (BC) stem cell (BCSC) marker. Primary breast tumor cells having CD24-negativity together with CD44-positivity is known to maintain high metastatic potential. However, the functional role of CD24 gene in triple-negative BC (TNBC), an aggressive subtype of BC, is not well understood. While the significance o...

Background Intestinal epithelial cell (IEC) mitochondrial dysfunction involvement in inflammatory bowel diseases (IBD), including Crohn’s disease affecting the small intestine, is emerging in recent studies. As the interface between the self and the gut microbiota, IECs serve as hubs of bidirectional cross-talk between host and luminal microbiota....

Approximately one-third of endocrine-treated women with estrogen receptor alpha–positive (ER+) breast cancers are at risk of recurrence due to intrinsic or acquired resistance. Thus, it is vital to understand the mechanisms underlying endocrine therapy resistance in ER+ breast cancer to improve patient treatment. Mitochondrial fatty acid β-oxidatio...

Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions required for cellular energy demands. Not surprisingly, mutations that alter FAD binding to flavoproteins cause rare inborn errors of metabolism (IEMs) that disrupt liver function and render fasting intolerance, hepatic steatosis, and lipodystrop...

Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions required for cellular energy demands. Not surprisingly, mutations that alter FAD binding to flavoproteins cause rare inborn errors of metabolism (IEMs) that disrupt liver function and render fasting intolerance, hepatic steatosis, and lipodystrop...

Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions required for cellular energy demands. Not surprisingly, mutations that alter FAD binding to flavoproteins cause rare inborn errors of metabolism (IEMs) that disrupt liver function and render fasting intolerance, hepatic steatosis, and lipodystrop...

Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions required for cellular energy demands. Not surprisingly, mutations that alter FAD binding to flavoproteins cause rare inborn errors of metabolism (IEMs) that disrupt liver function and render fasting intolerance, hepatic steatosis, and lipodystrop...

In most eukaryotic cells fatty acid synthesis occurs in the cytoplasm as well as in mitochondria. However, the relative contribution of mitochondrial fatty acid synthesis (mtFAS) to the cellular lipidome of metazoans is ill-defined. Hence, we studied the function of the fly Mitochondria enoyl CoA reductase (Mecr), the enzyme required for the last s...

Biguanides such as metformin are one of the most widely administered anti-diabetic drugs. Biguanides can suppress OXPHOS by inhibiting the complex-I activity of the mitochondrial electron transport chain (ETC). Though metformin recently generated lots of hope in cancer therapy, several clinical trials showed only limited advantages for metformin in...

Breast cancer (BC) is one of the most commonly diagnosed cancers worldwide and the most common in women in the United States. The majority of the BC are estrogen receptor alpha positive (ER+) and are likely to respond to endocrine therapy. Tamoxifen and fulvestrant are the most widely used hormonal treatments for ER+ BC. However, nearly half of pat...

Therapeutic effect of tamoxifen (Tam) against ER+ breast cancer (BC) is known to be mediated by its binding to estrogen receptor-alpha (ERά/ESR1) and inhibiting estrogen signaling leading to altered gene expression. Besides this canonical mode of function, our pre-clinical studies had revealed a novel mechanism wherein ESR1 directly binds wild type...

Drug repurposing can overcome both substantial costs and the lengthy process of new drug discovery and development in cancer treatment. Some Food and Drug Administration (FDA)-approved drugs have been found to have the potential to be repurposed as anti-cancer drugs. However, the progress is slow due to only a handful of strategies employed to iden...

Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions required for cellular energy demands. Not surprisingly, mutations that alter FAD binding to flavoproteins cause rare inborn errors of metabolism (IEMs) that disrupt liver function and render fasting intolerance, hepatic steatosis, and lipodystrop...

Triple-negative breast cancer (TNBC) is an aggressive subtype without any effective targeted therapies and rapidly become resistant to generic chemotherapy. Therefore, there is an urgent need to develop new therapeutic strategies. Estrogen receptor beta (ER beta) levels are high in about 60-70% of TNBCs. Recent reports including the Cancer Genome A...

Potential differences and mechanism in metabolism among bladder cancer (BLCA) patients of diverse race or ethnicities remain largely unexplored. Even though the incidence rate of BLCA in African Americans (AA) is nearly half as that of European Americans (EA), but AA have the worst survival. We performed the transcriptomics and metabolomics profili...

The major limitations of DNA-targeting chemotherapy drugs include life-threatening toxicity, acquired resistance and occurrence of secondary cancers. Here, we report a small molecule, Carbazole Blue (CB), that binds to DNA and inhibits cancer growth and metastasis by targeting DNA-related processes that tumor cells use but not the normal cells. We...

We have previously reported that triple negative (TN) breast cancer (BC), an aggressive subtype of BC, has high dependency for mitochondrial fatty acid oxidation (FAO). We have also reported that FAO activates c-Src, one of the frequently upregulated oncopathways in TNBC. Our mechanism-based mathematical model of cancer metabolism by coupling the m...

While aerobic glycolysis, or the Warburg effect, has for a long time been considered a hallmark of tumor metabolism, recent studies have revealed a far more complex picture. Tumor cells exhibit widespread metabolic heterogeneity, not only in their presentation of the Warburg effect but also in the nutrients and the metabolic pathways they are depen...

Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma, small stature, skeletal anomalies, sparse brows/lashes, cataracts, and predisposition to cancer. Type 2 RTS patients with biallelic RECQL4 pathogenic variants have multiple skeletal anomalies and a significantly increased incidence of osteosarc...

A facile base-catalyzed hydrothermal method is used to synthesize a bifunctional luminomagnetic Er³⁺/Yb³⁺ doped Gd2O3 nanorods material. The as-synthesized nanorods material is investigated for structural/microstructural, upconversion, and magnetic properties. The intense emission bands at 520 nm, 540 nm, and 654 nm are observed upon excitation wit...

Compared to hormone receptor (HR) positive breast cancer (BC), basal or triple-negative BC (TNBC) suffers a poor prognosis, attributed to the limited understanding of its driver signaling pathways. Although TNBC exhibits unique characteristics, clinical benefit from currently available targeted therapies is limited, and new therapeutic strategies a...

Paneth cell defects in Crohn’s disease (CD) patients (called the Type I phenotype) are associated with worse clinical outcomes. Recent studies have implicated mitochondrial dysfunction in Paneth cells as a mediator of ileitis in mice. We hypothesized that CD Paneth cells exhibit impaired mitochondrial health and that mitochondrial-targeted therapeu...

Cancer cells have the plasticity to adjust their metabolic phenotypes for survival and metastasis. A developmental programme known as epithelial-to-mesenchymal transition (EMT) plays a critical role during metastasis, promoting the loss of polarity and cell–cell adhesion and the acquisition of motile, stem-cell characteristics. Cells undergoing EMT...

While aerobic glycolysis, or the Warburg effect, has for a long time been considered a hallmark of tumor metabolism, recent studies have revealed a far more complex picture. Tumor cells exhibit widespread metabolic heterogeneity, utilizing glycolysis, oxidative phosphorylation, or both, and can switch between different metabolic phenotypes. A frame...

Cancer cells have the plasticity to adjust their metabolic phenotypes for survival and metastasis. During metastasis, a developmental program known as the epithelial-mesenchymal transition (EMT) plays a critical role. There is extensive cross-talk between metabolism and EMT, but how this leads to coordinated physiological changes is still uncertain...

That endocrine therapy or HER2 targeted therapies are not effective against TNBC makes it the most difficult breast cancer subtype to treat. Although these tumors initially respond to chemotherapy, there is high risk of relapse. Therefore, there is urgent need to develop new therapeutic strategies against these aggressive cancers. Reports including...

c-Src (Src) is a proto-oncogene involved in signaling that culminates in the control of multiple biological functions. Src is also one of the most frequently upregulated pathways in triple negative breast cancer (TNBC). Dysregulation of Src has been detected in TNBC and is strongly associated with tumor metastasis and poor prognosis. However, even...

Triple negative breast cancer (TNBC) is one of non-targetable cancers which are still poorly understood for the driver pathways and therapeutic targets. Over the past decade, cancer metabolism researches have a huge advance. Thus, it has enhanced our understanding on metabolic reprogramming in cancer therapy. We have previously shown that metabolic...

Whether estrogen receptor beta (ERβ/) is a pro- or anti-oncogenic protein in breast cancer has been controversial. ERβ levels are generally high in triple-negative breast cancer (TNBC). Reports including the Cancer Genome Atlas (TCGA) show that about 80% of TNBC express mutant p53 and it is a major driver of these cancers. We tested the hypothesis...

Ataxia telangiectasia mutated (ATM), a critical DNA damage sensor with protein kinase activity,is frequently altered in human cancers including mantle cell lymphoma (MCL). Loss of ATM protein is linked to accumulation of nonfunctional mitochondria and defective mitophagy, in both murine thymocytes and in A-T cells. However, the mechanistic role of...

Dysregulation of the mammalian target of rapamycin (mTOR) signaling, which is mediated by two structurally and functionally distinct complexes, mTORC1 and mTORC2, has been implicated in several neurological disorders1–3. Individuals carrying loss-of-function mutations in the phosphatase and tensin homolog (PTEN) gene, a negative regulator of mTOR s...

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Anabolic resistance and impaired myocellular qualitycontribute to age-related sarcopenia, which exacer-bates with obesity. Diet-induced muscle mass lossis attenuated by resistance or aerobic plus resis-tance exercise compared to aerobic exercise inobese elderly. We assessed chronic effects of weightloss plus different exercise modalities on musclep...

Metabolic plasticity allows cancer cells to adjust their metabolic phenotypes to grow and metastasize in hostile environments. Both glycolysis and oxidative phosphorylation (OXPHOS) are adapted by cancer cells to meet their bioenergetic and biosynthetic requirements in a context-dependent manner. Despite the advance in studies focusing only on glyc...

Metabolic plasticity allows cancer cells to adjust their metabolic phenotypes to grow and metastasize in hostile environments. Both glycolysis and oxidative phosphorylation (OXPHOS) are adapted by cancer cells to meet their bioenergetic and biosynthetic requirements in a context-dependent manner. Despite the advance in studies focusing only on glyc...

Background: Anti-tumorigenic versus pro-tumorigenic roles of estrogen receptor-beta (ESR2) in breast cancer (BC) remain unsettled. We investigated the potential of TP53 status to be a determinant of the bi-faceted role of ESR2 and associated therapeutic implications for triple negative BC (TNBC). Methods: ESR2-TP53 interaction was analyzed with...

Precisely measuring tumor-associated alterations in metabolism clinically will enable the efficient assessment of therapeutic responses. Advances in imaging technologies can exploit the differences in cancer-associated cell metabolism as compared to normal tissue metabolism, linking changes in target metabolism to therapeutic efficacy. Metabolic im...

This abstract was withdrawn by the authors. Citation Format: Das GM, Kulkarni S, Oturkar C, Edge SB, Wilton JH, Wang J, Swetzig WM, Adjei AA, Bies R, Hutson AD, Morrison CD, Kaipparettu BA, Groman A, Kumar S, Capuccino H. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelph...

Among breast cancers (BCs), the driver pathways and therapeutic targets are still poorly understood for triple negative (TN) BCs. Advances in cancer metabolism research over the last decade have enhanced our understanding on metabolic reprogramming in cancer therapy. We have previously shown that metabolic reprogramming to fatty acid β-oxidation (F...

c-Src (Src) is a proto-oncogene involved in signaling that culminates in the control of multiple biological functions. Src is also one of the most frequently upregulated pathways in triple negative breast cancer (TNBC). Dysregulation of Src has been detected in TNBC and is strongly associated with tumor metastasis and poor prognosis. However, even...

Significance Metabolic plasticity allows cancer cells to adjust their metabolic phenotypes to adapt in hostile environments. There is an urgent need to understand the cross-talk between gene regulation and metabolic pathways underlying cancer metabolic plasticity. We establish a theoretical framework to decode the coupling of gene regulation and me...

Quantum dots encompass a broad spectrum of optical, catalytic, and electrochemical properties bringing in novel applications in catalysis, imaging, displays, and optoelectronics. Herein, the unanticipated broad‐spectrum light absorption and high fluorescence quantum yield in fluorinated boron nitride (FBN) quantum dots are discussed. A heterostruct...

Metabolic plasticity enables cancer cells to switch their metabolism phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) during tumorigenesis and metastasis. However, it is still largely unknown how cancer cells orchestrate gene regulation to balance their glycolysis and OXPHOS activities for better survival. Here, we establish a t...

Instantaneous adhesion between different materials is a requirement for several applications ranging from electronics to biomedicine. Approaches like surface patterning, chemical cross-linking, surface modification, and chemical synthesis have been adopted to generate temporary adhesion between various materials and surfaces. Because of the lack of...

c-Src is a proto-oncogene involved in signaling that culminates in the control of multiple biological functions. Src is also one of the most frequently upregulated pathways in triple negative breast cancer (TNBC). Dysregulation of Src has been detected in TNBC and is strongly associated with tumor metastasis and poor prognosis. However, even after...

Bio-derived materials could play an important role in future sustainable green and health technologies.This work reports the synthesis of a unique egg white-based bio-derived material showing excellent stiffness and ductility by polymerizing it with primary amine-based chemical compounds to form strong covalent bonds. As shown by both experiments a...

c‐Src is a commonly upregulated oncogene in colorectal cancer. High fat diet (HFD) augments the numbers and function of Lgr5 + intestinal stem cells (ISCs), increasing the capacity of these stems cells to initiate tumors. Discoveries in triple negative breast cancer models and patient specimens suggest that mitochondrial reprogramming to fatty acid...

Aerobic glycolysis, also referred to as the Warburg effect, has been regarded as the dominant metabolic phenotype in cancer cells for a long time. More recently, it has been shown that mitochondria in most tumors are not defective in their ability to carry out oxidative phosphorylation (OXPHOS). Instead, in highly aggressive cancer cells, mitochond...

The unfolded protein response (UPR) is a cellular homeostatic mechanism that is activated in many human cancers and plays pivotal roles in tumor progression and therapy resistance. However, the molecular mechanisms for UPR activation and regulation in cancer cells remain elusive. Here, we show that oncogenic MYC regulates the inositol-requiring enz...

Triple-negative breast cancers (TNBCs) represent aggressive heterogeneous subtype of breast cancer with poor clinical outcome. TNBCs have been reported to have high levels of replication stress due to i) various oncogene activations (C-myc or EGFR) ii) germline BRCA mutations iii) “BRCAness” in the absence of BRCA mutations in sporadic TNBCs. Repli...

Despite altered metabolism being an accepted hallmark of cancer, it is still not completely understood which signaling pathways regulate these processes. Given the central role of androgen receptor (AR) signaling in prostate cancer, we hypothesized that AR could promote prostate cancer cell growth in part through increasing glucose uptake via the e...

Carbon-based nanomaterials have garnered a lot of attention in the research of yesteryear. Here this study reports a composite based on fluorinated graphene oxide—a multifunctional subsidiary of graphene; and iron oxide nanoparticles as a contrast agent for magnetic resonance imaging (MRI). Extensive structural and functional characterization is ca...

Smoking is a major risk factor for the development of Bladder Cancer (BLCA); however, the functional consequences of the carcinogens in tobacco smoke and BLCA-associated metabolic alterations remains poorly defined. We assessed the metabolic profiles in BLCA smokers and non-smokers, and identified the key alterations in their metabolism. Liquid Chr...

Carbon based nanomaterials garnered a lot of attention in biomedical research of yesteryear. Here we report a composite based on fluorinated graphene oxide (FGO) - a multifunctional subsidiary of graphene; and iron oxide nanoparticles as efficient contrast agents for magnetic resonance imaging (MRI). Extensive structural and functional characteriza...

Rare-earth free and biocompatible two dimensional carbon based boron oxynitride (2D BCNO) nanophosphors were synthesized using facile auto-combustion of inexpensive compounds such as urea, boric acid and polyethylene glycol at ambient atmosphere and relatively low temperatures. The surface morphology and microstructure images indicate that the nano...

Peripheral blood chronic lymphocytic leukemia (CLL) cells are quiescent but have active transcription and translation processes, suggesting that these lymphocytes are metabolically active. Based on this premise, the metabolic phenotype of CLL lymphocytes was investigated by evaluating the two intracellular ATP-generating pathways. Metabolic flux wa...

Compared to hormone regulated/responsive (ER+) breast cancer (BC), triple negative BC (TNBC) patients have a worse overall survival, a significantly shorter disease-free survival, and a shorter post-recurrence survival. Using transmitochondrial cybrid (cybrid) (compares different mitochondria under a common defined nuclear background)-based discove...

Abnormal metabolism is a hallmark of cancer, yet its regulatory mechanism is poorly understood. Cancer cells were considered to mostly utilize glycolysis, referred to as the Warburg effect. However recent evidence suggests that oxidative phosphorylation also plays a crucial role during cancer progression. Here we utilized a systems biology approach...

Background: Triple-negative breast cancers (TNBC) are the most aggressive forms of breast cancer and almost 60% of patients with TNBCs develop chemo-resistance, leading to recurrence, poor prognosis and poor survival. TNBCs have been reported to have high levels of replication stress, which plays pivotal role in genomic instability, and therapy res...

Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a sy...

For triple negative breast cancer (TNBC), the driver pathways are still poorly understood. Advances in cancer metabolism research over the last decade have enhanced and modified our understanding on Warburg effect. It is now known that mitochondria in tumors are not always defective in their ability to carry out oxidative phosphorylation. Instead,...

Nanoparticles exhibiting both magnetic and luminescent properties are need of the hour for many biological applications. A single compound exhibiting this combination of properties is uncommon. Herein, we report a strategy to synthesize a bifunctional luminomagnetic Gd2−xEuxO3 (x = 0.05 to 0.5) nanorod, with a diameter of ~20 nm and length in ~0.6...

The precise molecular alterations driving castration-resistant prostate cancer (CRPC) are not clearly understood. Using a novel network-based integrative approach, here, we show distinct alterations in the hexosamine biosynthetic pathway (HBP) to be critical for CRPC. Expression of HBP enzyme glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) is...

Compared to other subtypes of tumors, triple negative breast cancers (TN BCa) currently suffer from limited knowledge on its etiology and treatment options. Transmitochondrial cybrids (cybrid) and multiple OMICs approaches were used to understand mitochondrial reprogramming and mitochondria-regulated cancer pathways in TN BCa. Analysis of cybrids a...

The precise molecular alterations driving castration-resistant prostate cancer (CRPC) are not clearly understood. Using a novel network-based integrative approach, here, we show distinct alterations in the hexosamine biosynthetic pathway (HBP) to be critical for CRPC. Expression of HBP enzyme glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) is...

R software code used for integrative analysis

This is the matched gene expression and metabolomics data that was used for the integrative analysis. The metabolomics data was originally published in Nature 2009, PMID 19212411.