A5012506385- Sulfur Compounds in Biology
- Genetics, Aging, and Longevity in Model Organisms
- Dietary Effects on Health
- Diet and metabolism studies
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Circadian rhythm and melatonin
- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Amino Acid Enzymes and Metabolism
- Birth, Development, and Health
- Folate and B Vitamins Research
- Endoplasmic Reticulum Stress and Disease
- Epigenetics and DNA Methylation
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Nutritional Studies and Diet
- Virus-based gene therapy research
- DNA Repair Mechanisms
- Fibroblast Growth Factor Research
- Telomeres, Telomerase, and Senescence
- Genomics, phytochemicals, and oxidative stress
- Proteoglycans and glycosaminoglycans research
- Liver Disease Diagnosis and Treatment
- Air Quality and Health Impacts
- Biochemical effects in animals
Cleveland Clinic Lerner College of Medicine
2017-2024
Birmingham Women’s and Children’s NHS Foundation Trust
2021-2024
Cleveland Clinic
2020-2024
Case Western Reserve University
2020-2024
Case Comprehensive Cancer Center
2021-2024
Birmingham Children's Hospital
2020-2023
Harvard University
2012-2022
St Christopher's Hospice
2016
Pediatrics and Genetics
2015
University of Rochester
2006-2014
A genome stability regulator integrates DNA repair and stress signaling pathways.
The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, mole-rats have an extraordinary resistance cancer as tumors never been observed in these rodents. Furthermore, we show that combination of activated Ras and SV40 LT fails induce robust anchorage-independent growth cells, while it readily transforms mouse fibroblasts. mechanisms responsible for were unknown. Here fibroblasts display hypersensitivity contact inhibition,...
Abstract Hydrogen sulfide (H 2 S) plays important roles in metabolism and health. Its enzymatic generation from sulfur-containing amino acids (SAAs) is well characterized. However, the existence of non-enzymatic H S production SAAs, chemical mechanism, its biological implications remain unclear. Here we present vitro blood via a reaction specific for SAA cysteine serving as substrate requires coordinated catalysis by Vitamin B 6 , pyridoxal(phosphate), iron under physiological conditions. An...
Summary In multicellular organisms, telomerase is required to maintain telomere length in the germline but dispensable soma. Mice, for example, express somatic and tissues, while humans almost exclusively germline. As a result, when telomeres of human cells reach critical enter irreversible growth arrest called replicative senescence. Replicative senescence believed be an anticancer mechanism that limits cell proliferation. The difference between mice led hypothesis repression has evolved as...
Blind mole rats Spalax (BMR) are small subterranean rodents common in the Middle East. BMR is distinguished by its adaptations to life underground, remarkable longevity (with a maximum documented lifespan of 21 y), and resistance cancer. Spontaneous tumors have never been observed spalacids. To understand mechanisms responsible for this resistance, we examined growth fibroblasts vitro species judaei golani . cells proliferated actively 7–20 population doublings, after which began secreting...
Large, long-lived species experience more lifetime cell divisions and hence a greater risk of spontaneous tumor formation than smaller, short-lived species. are thus expected to evolve elaborate suppressor systems. In previous work, we showed that telomerase activity coevolves with body mass, but not lifespan, in rodents: is repressed the somatic tissues large rodent remains active small ones. Without activity, telomeres replicating cells become progressively shorter until, at some critical...
Host nutrition can affect the outcome of parasitic diseases through metabolic effects on host immunity and/or parasite. Here we show that modulation mouse immunometabolism brief restriction food intake (dietary restriction, DR) prevents neuropathology in experimental cerebral malaria (ECM). While no are detected parasite growth, DR reduces accumulation peripheral tissues including brain, and increases clearance spleen. Leptin, a host-derived adipokine linking appetite, energy balance immune...
Abstract Hydrogen sulfide (H 2 S) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SS n H). Despite the known importance of persulfidation, tissue-specific persulfidome profiles and their associated functions are not well characterized, specifically under conditions interventions to modulate H S production. We hypothesize dietary restriction (DR), which increases lifespan can boost production, expands persulfidomes. Here, we find enriched in liver,...
Glioblastoma (GBM) remains among the deadliest of human malignancies, and emergence cancer stem cell (CSC) phenotype represents a major challenge to durable treatment response. Because environmental lifestyle factors that impact CSC populations are not clear, we sought understand consequences diet on enrichment. We evaluated disease progression in mice fed an obesity-inducing high-fat (HFD) versus low-fat, control diet. HFD resulted hyperaggressive accompanied by enrichment shortened...
Rad51 protein, involved in homologous recombination, is overexpressed a variety of tumors, and its expression correlated with poor prognosis. Here we propose to exploit the overexpression cancer cells design promoter-based anticancer therapy. On average, mRNA protein levels are increased four- sixfold, respectively. Serendipitously, discovered that when ORF replaced another ORF, difference promoter activity between normal increases an average 840-fold maximum 12,500-fold. This dramatic has...
Dietary restriction (DR) as a means to increase longevity is well-established in number of model organisms from yeast primates. DR also improves metabolic fitness and increases resistance acute oxidative, carcinogenic toxicological stressors - benefits with more immediate potential for clinical translation than increased lifespan. While the detailed mechanism action remains unclear, conceptual framework involving an adaptive, or hormetic response stress nutrient/energy deprivation has been...
Chronic 1% metformin treatment is nephrotoxic in mice, but this dose may nonetheless confer health benefits if given intermittently rather than continuously. Here, we examined the effects of every-other week (EOW) or two consecutive weeks per month (2WM) on survival 2-year-old male mice fed standard chow. EOW and 2WM had comparable life span compared with control mice. A significant reduction body weight within first few was observed without impact food consumption energy expenditure....
Hydrogen sulfide (H2S) at the right concentration is associated with numerous health benefits in experimental organisms, ranging from protection ischemia/reperfusion injury to life span extension. Given considerable translation potential, two major strategies have emerged: supplementation of exogenous H2S and modulation endogenous metabolism. Recent Advances: Recently, it was reported that hepatic production capacity increased best-characterized mammalian models extension, dietary...
Protein restriction (PR) is important for the benefits of dietary on longevity and stress resistance, but relevant nutrient sensors downstream effectors in mammals remain poorly defined. We used PR-mediated protection from hepatic ischemia reperfusion injury to probe genetic requirements evolutionarily conserved GCN2 mTORC1 resistance. One week PR reduced free amino acids circulating growth factors, activating repressor tuberous sclerosis complex (TSC). However, although was dispensable...