A5039629265- Sirtuins and Resveratrol in Medicine
- CRISPR and Genetic Engineering
- Adipose Tissue and Metabolism
- Cancer, Hypoxia, and Metabolism
- Genetics, Aging, and Longevity in Model Organisms
- Immune cells in cancer
- Extracellular vesicles in disease
- Evolution and Genetic Dynamics
- RNA modifications and cancer
- Caveolin-1 and cellular processes
- Epigenetics and DNA Methylation
- Cancer, Lipids, and Metabolism
- Biochemical effects in animals
- Diet and metabolism studies
- Insect symbiosis and bacterial influences
- Metabolomics and Mass Spectrometry Studies
- Lipid metabolism and biosynthesis
- Neurological Complications and Syndromes
- Insect behavior and control techniques
- Heme Oxygenase-1 and Carbon Monoxide
- Chemotherapy-induced organ toxicity mitigation
- Nutrition and Health in Aging
- Regulation of Appetite and Obesity
- Polyamine Metabolism and Applications
- Tryptophan and brain disorders
Cornell University
2022-2025
Weill Cornell Medicine
2022-2025
Tsinghua University
2016-2022
Harvard University
2017-2019
Diet influences macronutrient availability to cells, and although mechanisms of sensing dietary glucose amino acids are well characterized, less is known about lipids. We defined a nutrient signaling mechanism involving fatty acid–binding protein 5 (FABP5) mechanistic target rapamycin complex 1 (mTORC1) that activated by the essential polyunsaturated acid (PUFA) ω-6 linoleic (LA). FABP5 directly bound regulatory-associated mTOR (Raptor) enhance formation functional mTORC1 substrate binding,...
Calorie restriction (CR) extends lifespan from yeast to mammals. SIRT6 is a member of the sirtuin family NAD+-dependent histone deacetylases, which responsible for mediating effects CR. The transcription factor NF-κB, involved in inflammation and aging, has been shown be regulated by SIRT6. Here we describe crucial role aging inflammation. We show that CR had improved renal insufficiency enhanced expression after 6-month treatment aged mice. Culture cells low glucose (LG) conditions also...
ABSTRACT Background Cachexia is a wasting syndrome associated with imbalanced energy metabolism and loss of adipose muscle tissues contributes to morbidity mortality in ageing as well patients severe chronic diseases, including cancer. At present, there are no treatments addressing cachexia that have reached validation be used the clinic. In this study, we investigate protective role SIRT6, an important regulator homeostasis health preservation, against Lewis lung carcinoma (LLC)–induced...
Genome-wide screens in Drosophila cells have offered numerous insights into gene function, yet a major limitation has been the inability to stably deliver large multiplexed DNA libraries cultured allowing barcoded pooled screens. Here, we developed site-specific integration strategy for library delivery and performed genome-wide CRISPR knockout screen S2R+ cells. Under basal growth conditions, 1235 genes were essential cell fitness at false-discovery rate of 5%, representing...
Abstract The systemic metabolic shifts that occur during aging and the local alterations of a tumor, its stroma their communication cooperate to establish unique tumor microenvironment (TME) fostering cancer progression. Here, we show methylmalonic acid (MMA), an aging-increased oncometabolite also produced by aggressive cells, activates fibroblasts in TME, which reciprocally secrete IL-6 loaded extracellular vesicles (EVs) drive progression, drug resistance metastasis. cancer-associated...
Serine/one-carbon metabolism provides critical resources for nucleotide biosynthesis and epigenetic maintenance is thus necessary in cancer cell growth, although the detailed regulatory mechanisms remain unclear. We uncover a role of glycogen synthase kinase 3 (GSK3) regulating expression serine/one-carbon metabolic enzymes. Nuclear enrichment GSK3 significantly suppresses genes that mediate de novo serine synthesis, including PHGDH, PSAT1, PSPH, one-carbon metabolism, SHMT2 MTHFD2. FRAT1...
Abstract Aging‐associated microbial dysbiosis exacerbates various disorders and dysfunctions, is a major contributor to morbidity mortality in the elderly, but underlying cause of this aging‐related syndrome confusing. SIRT6 knockout (SIRT6 KO) mice undergo premature aging succumb death by 4 weeks, are therefore useful as research model. Here, fecal microbiota transplantation from KO into wild‐type (WT) phenocopies gut observed mice. Conversely, an expanded lifespan was when transplanted...
Abstract Enhanced cholesterol synthesis and storage in lipid droplets are strongly associated with cancer aggressiveness, particularly lipid-rich hormone-sensitive cancers such as prostate cancer. While tumor cells tightly regulate anabolism catabolism response to nutrient states, the mechanisms that sense status drive these processes remain poorly understood. Emerging evidence highlights mitochondria key hubs of signal transduction, mitochondrial metabolites serving pivotal signaling...
Obesity-related renal diseases have been a worldwide issue. Effective strategy that prevents high fat-diet induced damage is of great significance. Resveratrol, natural plant polyphenol, famous for its antioxidant activity, cardioprotective effects and anticancer properties. However whether resveratrol can play role in the treatment unknown. In this study, we added normal glucose or medium provide evidences protects against high-glucose triggered oxidative stress cell senescence. Moreover,...
Sirtuin 6 (SIRT6), as a NAD + -dependent deacetylase, plays an indispensable role in the regulation of health and physiology. Loss SIRT6 causes spontaneous colitis mice makes intestinal epithelial cells prone to stress. However, whether overexpression increases resistance remains unknown. Here, vivo results demonstrated that attenuates DSS-induced terms clinical manifestations, histopathological damage, loss tight junction function imbalanced microenvironment. Additionally, we also found...
Abstract Mammalian sirtuin 6 (SIRT6) is involved in the regulation of many essential processes, especially metabolic homeostasis. SIRT6 knockout mice undergo premature aging and die at age ~4 weeks. Severe glycometabolic disorders have been found mice, whether a dietary intervention can rescue remains unknown. In our study, we that same calorie intake, high‐fat diet dramatically increased lifespan to 26 weeks (males) 37 (females), reversed multi‐organ atrophy, reduced body weight,...
Abstract High‐throughput screens in Drosophila melanogaster cell lines have led to discovery of conserved gene functions related signal transduction, host‐pathogen interactions, ion transport, and more. CRISPR/Cas9 technology has opened the door new types large‐scale cell‐based screens. Whereas array‐format require liquid handling automation assay miniaturization, pooled‐format screens, which reagents are introduced at random bulk, can be done a standard lab setting. We provide detailed...
Abstract Spermatogenesis‐associated protein 4 (SPATA4) is conserved across multiple species. However, the function of this gene remains largely unknown. In study, we generated Spata4 transgenic mice to explore tissue‐specific SPATA4. overexpression displayed increased subcutaneous fat tissue compared with wild‐type littermates at an old age, while difference was not observed in younger mice. Aging‐induced ectopic distribution, inflammation, and insulin resistance were also significantly...
Significance Synthetic sick or lethal (SS/L) interactions occur when disruption of two genes reduces cell viability to a greater extent than expected based on the individual gene disruptions. SS/L involving tumor suppressors represent candidate drug targets for cancers because treatment is kill cells carrying suppressor mutation but leave healthy unaffected. Identification vital importance develop new therapies tumorigenic disease. We have developed an RNAi-based approach called variable...
Like many diseases, cancer is influenced by oxidative stress. Increases in stress caused factors such as environmental stressors and unhealthy diets can increase the risk of worsen prognoses. However, does not always promote cancer. On contrary, chemotherapeutics induce production to kill cells. The tumor microenvironment (TME) another factor progression. Stromal cells, a part TME, communicate with cells through extracellular vesicles (EVs) - primary vehicles for delivery messengers,...
Abstract Genome-wide screens in Drosophila cells have offered numerous insights into gene function, yet a major limitation has been the inability to stably deliver large multiplexed DNA libraries cultured allowing barcoded pooled screens. Here, we developed site-specific integration strategy for library delivery and performed genome-wide CRISPR knockout screen S2R+ cells. Under basal growth conditions, 1235 genes were essential cell fitness at false-discovery rate of 5%, representing...
Abstract Lung cancer is the leading cause of cancer-related deaths in United States. Identifying new factors that promote drug resistance critical to restoring sensitivity and improving patient outcomes. Methylmalonic acid (MMA) a dicarboxylic by-product propionate metabolism. MMA levels rise serum with age are associated mortality (the higher MMA, worse mortality). We recently asked whether this metabolite had functional impact showed treating non-small cell lung (NSCLC) cells vitro...