Rexford S. Ahima - US grants
Affiliations: | University of Pennsylvania, Philadelphia, PA, United States |
Area:
Neuroscience Biology, Molecular Biology, NutritionWe are testing a new system for linking grants to scientists.
The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Rexford S. Ahima is the likely recipient of the following grants.| Years | Recipients | Code | Title / Keywords | Matching score |
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| 2002 — 2010 | Ahima, Rexford S | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
Cns Action of Appetite Suppressant Aminosterol @ University of Pennsylvania DESCRIPTION (provided by applicant): The obesity epidemic has been linked to increasing incidence of diabetes, cardiovascular disease and other complications. Diet and exercise are essential to weight management;however, it is obvious that many patients would require drug treatment to achieve and maintain weight reduction. The goal of this grant is to understand the actions of a novel aminosterol, which we have found to potently decrease body weight. During the past 3 years, we have shown that the anti-obesity effect of MSI-1436 is mediated through inhibition of food intake as well as increased metabolic rate. Unlike other anorectics, a single intraperitoneal or intracerebroventricular (i.c.v.) injection of MSI-1436 decreases body weight for several days. Moreover, MSI-1436 stimulates insulin response and prevents steatosis. An intact leptin signaling is not critical to the action of MSI-1436, since this compound is effective in ob/ob and db/db mice, fa/fa rats, and diet-induced obese mice. In contrast, agouti (Ay/a) mice are less responsive to MSI-1436, suggesting that melanocortin (MC)3/4 receptors are crucial its action in the brain. MSI-1436 binds to hypothalamic and other brain areas which mediate energy balance, and strongly induces Fos-immunoreactivity in the paraventricular hypothalamic nucleus and to a lesser extent in the arcuate, ventromedial nuclei, central amygdala and nucleus solitarius. A CNS action of MSI-1436 is further evident by the suppression of agouti-related peptide (AGRP) and neuropeptide Y (NPY) in hypothalamus. Hence, we hypothesize that MSI-1436 regulates energy balance and glucose through similar hypothalamic circuits. Specific Aim 1 will investigate whether treatment with NPY or AGRP can reverse the effect of MSI-1436. Moreover, we will determine whether deletion of NPY, AGRP and MC4 receptor genes block the action of MSI-1436. Specific Aim 2 will investigate the roles of NPY, AGRP and MC4 receptor in mediating the effect of MSI-1436 on glucose. Specific Aim 3 will evaluate the effects of MSI-1436 on hypothalamic enzymes, i.e. AMP kinase and fatty acid synthase, implicated in energy homeostasis. Finally, specific Aim 4 will determine whether activation of hypothalamic AMP kinase is able to prevent the effect of MSI-1436, as has been shown for various anorectics. Understanding of the central neuronal actions MSI-1436 may elucidate novel targets for the treatment of obesity and related diseases. |
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| 2006 — 2010 | Ahima, Rexford S | P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Cns Effects of Adipokines On Metabolism @ University of Pennsylvania Obesity has reached epidemic proportions and poses serious public health challenges, in particular type 2 diabetes, cardiovascular disease, sleep apnea, osteoarthritis and cancer. Adipocyte hormones may provide key insights into the pathogenesis of obesity-related diseases. Leptin and adiponectin stimulate fatty acid oxidation, decrease lipid levels and increase insulin sensitivity. In contrast, resistin decreases insulin sensitivity, and increases glucose and lipids. Leptin acts in the CMS to suppress appetite and increase energy expenditure, but also has direct effects on peripheral tissues. Adiponectin and resistin have direct actions on liver and muscle, but recent observations suggest that these adipokines also have central effects. We hypothesize that the divergent effects of these adipocytes on metabolism are mediated, at least in part, through distinct neuronal targets and signaling pathways in the hypothalamus. Specific Aim 1 will compare the effects of CMS administration of leptin, adiponectin and resistin on energy and glucose metabolism. We will examine the regulation of peripheral glucose fluxes using insulin clamp and radioactive tracer kinetics. Based on our preliminary studies showing an attenuation of the CMS effects of leptin and adiponectin in agouti mice, we will determine whether the opposite effects of leptin/adiponectin versus resistin on glucose levels is mediated through melanocortin (MC)4 receptor signaling. Specific Aim 2 will determine the sites of action of these adipocyte hormones in the hypothalamus, using Fos immunohistochemistry and in situ hybridization. Finally, Specific Aim 3 will determine whether the opposing metabolic effects of leptin, adiponectin and resistin occur through AMP-kinase and SOCS-3 in the hypothalamus. We will test the hypothesis that central administration of resistin antagonizes the central effects of leptin and adiponectin on metabolism, through reciprocal regulation of AMPK, SOC-3, or both signaling pathways. Understanding the hypothalamic and signaling pathways that mediate the effects of leptin, adiponctin and resistin will provide novel insights into the pathophysiology of obesity and diabetes that will facilitate novel diagnostic and treatment strategies. |
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| 2006 — 2016 | Ahima, Rexford S | P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Mouse Metabolic Phenotyping Core @ University of Pennsylvania ABSTRACT NOT PROVIDED |
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| 2007 — 2016 | Ahima, Rexford S. | P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Mouse Phenotyping, Physiology, and Metabolism Core @ University of Pennsylvania The incidence of diabetes is increasing rapidly as a result of the obesity epidemic. The Mouse Phenotyping, Physiology and Metabolism Core supports the overall mission of the Penn DRC to prevent, treat, and cure diabetes mellitus. Our understanding of the pathogenesis of diabetes, obesity and other metabolic disorders has benefited from the use of gene targeting methodology in mice to elucidate molecular mechanisms. However, such efforts are often hampered by a lack of facilities or expertise for metabolic phenotyping. The Mouse Phenotyping, Physiology and Metabolism Core provides investigators of the Penn Diabetes Research Center (DRC) with state-of-the-art, timely and cost-effective diagnostic studies in mice. The core offers consultation and experimental design, monitoring of feeding, drinking, energy expenditure, locomotor activity and sleep epochs using a Comprehensive Laboratory Animal Monitoring System (CLAMS), measurement of body composition using dual emission x-ray absorptiometry (DEXA) or nuclear magnetic resonance spectroscopy, and assessment of glucose homeostasis with glucose and insulin tolerance tests, and insulin clamp and radioactive tracer kinetics. Studies in the core are performed by two research specialists under the direction of Rexford Ahima. The core maintains a database of metabolic and hormonal parameters in mouse models of diabetes and obesity, and coordinates its services with other core laboratories, i.e. Islet Biology (Franz Matschinsky; Doris Stoffers), Radioimmunoassay and Biomarkers (Muredach Reilly), Transgenic and Chimeric (Nancy Cooke; Stephen Liebhaber), and Functional Genomics Core (Klaus Kaestner). These efforts facilitate in vivo metabolic phenotyping of mice, and the translation of ideas from the bench to mice, and ultimately to humans. |
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| 2012 — 2016 | Ahima, Rexford S. | P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Brain and Peripheral Metabolic Adaptations to Feeding Entrainment @ University of Pennsylvania Shift work, insufficient sleep and other disrupters of circadian activity increase the risk of metabolic syndrome, characterized by obesity, insulin resistance, dyslipidemia, hypertension, and cardiovascular morbidity. The next cycle of Project #3 will investigate interactions of the brain and peripheral organs in a feeding entrainment model in mice that mimic metabolic disorders resulting from circadian disruption in humans. Mice restricted to 5 hours feeding during the light cycle (L-Fed) develop hypothalamic leptin insensitivity and elevation of resistin levels in 1 week, followed by hepatic steatosis, insulin resistance and obesity. Hepatic CREB coactivator (Crtc2) is increased and Akt activation is blunted in L-Fed mice. We hypothesize that the signaling of leptin and resistin in the brain and liver are crucial for the pathogenesis of steatosis, insulin resistance and obesity in L-Fed mice. Aim 1 will determine how enhanced leptin sensitivity in the hypothalamus resulting from Tyr985 knock-in mutation in the leptin receptor or Socs3 deletion in AGRP and POMC neurons affects energy homeostasis, and glucose and lipid metabolism during feeding entrainment. Aim 2 will determine how leptin interacts with Crtc2 and Akt2 in the liver to regulate glucose and lipid metabolism during feeding entrainment. Aim 3 will determine whether resistin knockout mice are protected against insulin resistance during feeding entrainment, and whether Socs3 mediates resistin's ability to induce insulin resistance. The proposed studies will address critical mechanisms underiying the development of obesity and metabolic dysregulation in mice restricted to feeding during the day. The project will benefit from collaborations with other P01 investigators, and has the potential to provide novel pathophysiological mechanisms and therapies for obesity, diabetes and dyslipidemia associated with disruption of circadian rhythms. RELEVANCE (See instructions): Shift work and other activities that disrupt circadian rhythms increase the risk of obesity, diabetes and heart disease. This project will evaluate the metabolic effects of fat-derived hormones in a mouse model that resembles circadian disruption in humans. We will determine how disruption of the timing of feeding affects the actions of leptin and resistin, and how these fat hormones act in the brain and peripheral organs to cause fatty liver, insulin resistance and obesity. |
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| 2014 — 2018 | Ahima, Rexford S. Arnold, Steven E (co-PI) [⬀] Arvanitakis, Zoe |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Mechanisms Linking Insulin Resistance to Brain Structure, Pathology, and Function @ Rush University Medical Center DESCRIPTION (provided by applicant): Metabolic disturbances in particular type 2 diabetes mellitus (T2D), are common and increasing in incidence with contemporary lifestyles. T2D is associated with adverse health consequences, including impaired brain Yet, the causes and effects of insulin resistance in the brain are complex, as there are reciprocal interactions with other hormone signaling systems, in particular the adipokines (e.g., adiponectin and leptin) which strongly affect insulin sensitivity. Characterizing the molecular mechanisms that increase risk of AD for persons with insulin resistance is now of great scientific interest (PAS-11-029) and their elucidation may lead to novel therapeutic strategies. Insulin resistance, a core feature of T2D, may lead to increased brain pathology. T2D is modestly associated with cerebrovascular disease, but perhaps of even greater interest, recent data show brain insulin signaling abnormalities associated with AD pathology, specifically amyloid-ß and tau-related pathology as well. Furthermore, adipokine receptor expression abnormalities have also been found in AD. The overall goal of the proposed interdisciplinary collaborative project is to establish molecular mechanisms linking insulin, adopinectin, and leptin signaling in human brain, and determine how dysregulation in this network is associated with brain structure, pathology, and function, including AD and cognitive impairment. The proposed study will quantify markers of insulin, adiponectin, and leptin signaling, neurons and synapses, and use existing pathologic and clinical data from 200 community-dwelling women and men, with and without T2D and across a spectrum of cognitive function, who were well-characterized clinically and died and came to autopsy as participants in the Religious Orders Study (P30AG010161; R01AG015819). First, we will describe expression levels of brain insulin, adiponectin, and leptin pathway components in subjects with and without T2D (Aim 1). Then, using a novel ex-vivo stimulation paradigm in human postmortem tissue, we will experimentally test the stimulated responses and interactions of insulin and adipokine signaling in brain tissue (Aim 2). Finally, in the clinicopathologic translational component of the study, we will test the relations of insulin, adiponectin, and lepti signaling to brain structure (synaptic markers), pathology (amyloid-ß and tau), and function (cognition). Because insulin resistance is a common condition for which therapies are available, this study will break new ground in research of insulin and adipokine mechanisms in human brain, and show insulin resistance and adipokine dysfunction are associated with changes in the human brain at multiple levels, thus providing important data with potential to improve public health. |
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| 2018 | Ahima, Rexford S. Arnold, Steven E (co-PI) [⬀] Arvanitakis, Zoe |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Linking Peripheral and Brain Insulin Resistance to Ad Neuropathology and Cognition @ Rush University Medical Center PROJECT SUMMARY/ABSTRACT Type 2 diabetes mellitus (T2D) is common and results in enormous personal and societal costs. While many complications of T2D are well-established, less is known about the link between T2D and the brain, beyond associations with cerebrovascular disease, cognitive impairment, and dementia. Recent data show that insulin resistance (InsRes), a key component in T2D, may be present in the aging human brain itself and be associated with Alzheimer?s disease (AD) pathology, including amyloid-?, and cognitive impairment. A pressing scientific question is whether peripheral (systemic) InsRes is related to central (brain) InsRes and to AD. In response to PAR-17-031 calling for studies to elucidate metabolic regulation, and insulin signaling in particular, in AD, we propose an interdisciplinary project with the overall goal to examine associations of peripheral with central insulin resistance, and the associations of peripheral and central insulin resistance with AD neuropathology and cognitive function. The proposed study will take advantage of available biospecimens (frozen ante-mortem serum and peripheral blood mononuclear cells, and postmortem skeletal muscle and brain tissues) from which to quantify markers of chronic hyperglycemia and InsRes, and from which to use existing laboratory, clinical, and neuropathologic data, from 200 community-dwelling women and men, with and without T2D, who were well-characterized clinically and died and came to autopsy (R01AG17917). First, we will characterize peripheral (blood, muscle) and central (brain) InsRes in biospecimens, using two complementary approaches, including biochemical assays and an ex vivo stimulation paradigm to directly examine the insulin receptor signaling cascade (Aims 1 and 2). Next, we will test the hypothesis that peripheral InsRes is linked to central InsRes, and conduct additional analyses considering secondary markers of interest and whether other factors, such as sex and others, affect associations (Aim 3). Finally, in a translational aim, we will test the hypotheses that peripheral and central InsRes are associated with neurodegenerative and cerebrovascular neuropathology, and domain-specific cognitive function (Aim 4). Because InsRes is a key component of T2D for which therapies are available, this study which will test the link of peripheral and central InsRes, and neuropathology and cognition in persons with and without T2D, will fill major gaps in scientific knowledge and inform future research in the field of metabolism, insulin signaling, and AD, and provide important data with potential to improve public health. |
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