A5034125653- Adipose Tissue and Metabolism
- Immune Cell Function and Interaction
- Regulation of Appetite and Obesity
- Adipokines, Inflammation, and Metabolic Diseases
- Dietary Effects on Health
- Genetics and Neurodevelopmental Disorders
- Genetic Syndromes and Imprinting
- Stress Responses and Cortisol
- Neuroinflammation and Neurodegeneration Mechanisms
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- PI3K/AKT/mTOR signaling in cancer
- Pancreatic function and diabetes
- Autism Spectrum Disorder Research
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- RNA Interference and Gene Delivery
- Metabolism, Diabetes, and Cancer
- Grit, Self-Efficacy, and Motivation
- Epigenetics and DNA Methylation
- Kruppel-like factors research
- Exercise and Physiological Responses
- Hematopoietic Stem Cell Transplantation
- Cancer, Stress, Anesthesia, and Immune Response
- Animal Behavior and Welfare Studies
The Ohio State University
2017-2025
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2018-2022
Aging is associated with increased central nervous system inflammation, in large part due to dysfunctional microglia. Environmental enrichment (EE) provides a model for studying the dynamics of lifestyle factors development age-related neuroinflammation and microglial dysfunction. EE results improvements learning memory, metabolism, mental health variety animal models. We recently reported that implementing middle age promotes healthy aging. In present study, we investigated whether...
Social isolation (SI) is associated with an increased risk of mortality and various chronic diseases—including obesity—in humans. Murine studies probing SI metabolic outcomes remain inconsistent, due in part to a lack consideration for housing temperature. Such experiments typically occur at room temperature, subjecting mice cold stress. Single prevents social thermoregulation, further exacerbating stress obscuring psychosocial influences on metabolism In this study, C57BL/6 BALB/c male were...
Abstract The aging process and age‐related diseases all involve perturbed energy adaption impaired ability to cope with adversity. Brain‐derived neurotrophic factor (BDNF) in the hypothalamus plays important role regulation of balance. Our previous studies show that recombinant adeno‐associated virus (AAV)‐mediated hypothalamic BDNF gene transfer alleviates obesity, diabetes, metabolic syndromes both diet‐induced genetic models. Here we examined efficacy safety a built‐in autoregulatory...
Despite the large body of work describing tumor suppressor functions Phosphatase and tensin homologue deleted on chromosome ten (PTEN), its roles in adipose homeostasis adult animals are not yet fully understood. Here, we sought to determine role PTEN whole-body homeostasis. We genetically manipulated specific fat depots through recombinant adeno-associated viral vector (rAAV)-based gene transfer Cre recombinase PTENflox mice. Additionally, used a denervation agent, 6OHDA, assess sympathetic...
Abstract Prader-Willi syndrome (PWS) is a rare genetic disease that causes developmental delays, intellectual impairment, constant hunger, obesity, endocrine dysfunction, and various behavioral neuropsychiatric abnormalities. Standard care of PWS limited to strict supervision food intake growth hormone therapy, highlighting the unmet need for new therapeutic strategies. Environmental enrichment (EE), housing environment providing physical, social, cognitive stimulations, exerts broad...
It is challenging to genetically manipulate fat in adults. We demonstrate that intraperitoneal (i.p.) injection of an engineered adeno-associated virus (AAV) serotype Rec2 leads high transduction multiple visceral depots at a dose 1 2 orders lower than commonly used doses for systemic gene delivery. To target adipose tissue, we develop single AAV vector harboring two expression cassettes: one using the CBA promoter drive transgene and liver-specific albumin microRNA-targeting WPRE sequence...
With increases in life expectancy, it is vital to understand the dynamics of aging, their interaction with lifestyle factors, and connections age-related disease processes. Our work on environmental enrichment (EE), a housing environment boosting mental health, has revealed novel anticancer anti-obesity phenotype mediated by brain-fat axis: hypothalamic-sympathoneural-adipocyte (HSA) axis young animals. Here we investigated EE effects healthspan lifespan when initiated after middle age....
IL-15 is a proinflammatory cytokine that plays an essential role in the development and activation of natural killer (NK) cells. Adipose tissue acts as endocrine organ secretes cytokines important reservoir for lymphocytes. We hypothesized signaling adipose will activate expand NK cell population control tumor growth. recently developed adipocyte-targeting recombinant adeno-associated viral (rAAV) vector with minimal off-target transgene expression liver. Here, we used this rAAV system to...
As the elderly population grows, chronic metabolic dysfunction including obesity and diabetes are becoming increasingly common comorbidities.Hypothalamic inflammation through CNS resident microglia serves as a pathway between developing systemic aging pathologies.Despite understanding life-long process involving interactions individuals their environment, limited studies address dynamics of environment with or therapeutics.We previously demonstrated environmental enrichment (EE) is an...
Fibroblast growth factor 21 (FGF21) is a peptide hormone that serves as potent effector of energy homeostasis. Increasingly, FGF21 viewed promising therapeutic agent for type 2 diabetes, fatty liver disease, and other metabolic complications. Exogenous administration native has proved difficult due to unfavorable pharmacokinetic properties. Here, we utilized an engineered serotype adeno-associated viral (AAV) vector coupled with dual-cassette design selectively overexpress in visceral...
Obesity is becoming a global epidemic and risk factor for breast cancer. Environmental enrichment (EE), model recapitulating an active lifestyle, leads to leanness, resistance diet-induced obesity (DIO) One mechanism the activation of hypothalamic–sympathoneural–adipocyte (HSA) axis. This results in release norepinephrine onto adipose tissue inducing drop leptin. study aimed test effects EE on cancer onset progression while considering effect leptin by utilizing transgenic MMTV-PyMT as well...
Environmental enrichment (EE) is a physiological model to investigate brain-fat interactions. We previously discovered that EE activates the hypothalamic-sympathoneural adipocyte (HSA) axis via induction of brain-derived neurotrophic factor (BDNF), thus leading sympathetic stimulation white adipose tissue (WAT) and an anti-obesity phenotype. Here, we whether PTEN acts as downstream mediator HSA in EE. Mice were housed for 4- 16-week periods determine how regulates PTEN. Hypothalamic...
Macroenvironmental factors, including a patient's physical and social environment, play role in cancer risk progression. Our previous preclinical studies have shown that the enriched environment (EE) confers anti-obesity anti-cancer phenotypes are associated with enhanced adaptive immunity mediated by brain-derived neurotrophic factor (BDNF). Natural killer (NK) cells anti-viral properties, their absence or depletion is inferior clinical outcomes. In this study, we investigated effects of EE...
Abstract Aging is a complex physiological process that leads to the progressive decline of metabolic and immune function, among other biological mechanisms. As global life expectancy increases, it important understand determinants healthy aging—including environmental genetic factors—and thus slow onset or progression age-related disease. Environmental enrichment (EE) housing environment wherein laboratory animals engage with physical social stimulation. EE prime model influences on aging...
Individuals with Prader-Willi syndrome (PWS) exhibit several metabolic and behavioral abnormalities associated excessive food-seeking activity. PWS is thought to be driven in part by dysfunctional hypothalamic circuitry blunted responses peripheral signals of satiety. Previous work described a transcriptomic signature individuals PWS. Notably, patients exhibited downregulation genes involved neuronal development an upregulation neuroinflammatory genes. Deficiencies brain-derived neurotrophic...
Abstract: Social and environmental factors impact cancer energy balance profoundly. Years ago, our lab established the existence of a novel brain-fat interaction we termed “hypothalamic-sympathoneural-adipocyte (HSA) axis”, through which complex stimuli provided by an enriched environment regulate body composition, balance, development cancer. We have spent significant portion past decade to further characterize broad health benefits (for example, leanness, enhanced immune function,...
CD1d, a lipid Ag-presenting molecule for invariant NKT (iNKT) cells, is abundantly expressed on adipocytes and regulates adipose homeostasis through iNKT cells. CD1d gene expression was restored in visceral tissue of knockout (KO) mice to investigate the interactions between immune cells within tissue. We developed an adipocyte-specific targeting recombinant adeno-associated viral vector, with minimal off-target transgene liver, rescue KO mice, followed by assessment cell alternations...