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Daniela Salvemini, Ph.D., William Beaumont Professor, chair of the Department of Pharmacology and Physiology, and director of the Institute of Translational Neuroscience, in collaboration with Stephanie Geisler M.D., Ph.D., assistant professor of neurology at Washington University in St. Louis, have been awarded an ICTS/CTRFP grant award of $50,000. The grant 鈥淪phingolipidomics to identify small fiber neuropathy endotypes鈥� will examine whether sphingolipids can be used as biomarkers to identify subgroups of patients with small fiber neuropathy, which may lead to the development of personalized, targeted therapies. There currently are no effective treatments for small fiber neuropathy.

Andrew Butler, Ph.D., a professor of pharmacology and physiology, was awarded a two-year $416,625 grant by the National Institute of Aging titled "Methods for treating aging-related cognitive decline and reducing risk of AD/ADRD by enhancing the endogenous expression of adropin" (R21 AG087308). The investigators of this award recently reported community-dwelling adults with low levels of the secreted peptide adropin have increased risk of cognitive decline. Working with Andrew Nguyen, Ph.D., assistant professor of pharmacology and physiology, this funding will identify methods that induce long-term increases in the expression of the endogenous adropin protein. The long-term objective of this project is to determine whether three to six monthly injections of a long-acting drug are effective at preserving cognition in aging. Other members of the team include Susan Farr, Ph.D., professor of internal medicine; Geetika Aggarwal, Ph.D., staff research scientist; and Denise Smith, senior research assistant.

Butler was also awarded a two-year $416,625 grant by the National Institute of Aging titled "An investigation of the response of preclinical mouse models of dementia to adropin therapy" (R21 AG083451). Aging increases risk for cognitive decline due to neurodegenerative diseases, of which Alzheimer鈥檚 disease is most common. Working with Farr, the goals of this award are to test the efficacy of a small, soluble peptide in protecting the brain and cognitive functions in a mouse model of accelerated aging. The award will also determine whether loss of the peptide accelerates aging-related cognitive decline. This work will define the pathways through which this peptide preserves brain function in aging and could lead to a new therapy for treating Alzheimer鈥檚 disease. Other members of the team include Aggarwal and Aubin Moutal, Ph.D., assistant professor of pharmacology and physiology.

Liberty Francois-Moutal, Ph.D., a research assistant professor of pharmacology and physiology, was awarded a two-year $416,625 grant by the National Institute of Neurological Disorders and Stroke title 鈥淯nraveling how neuropathic pain synaptic transcriptome is signaled by G-quadruplex folds鈥� (R21 NS137054). This funding aims to examine the changes in the synaptic transcriptome of the primary-secondary sensory afferents structure occurring in the spinal cord during synaptic gain of function in neuropathic pain at different time points and different sex. Completion of this work will yield a comprehensive map of the transcriptomic changes that occur in the synapse during neuropathic pain and examine the factors that contribute to this highly polarized transcriptomic population. Other members of the team include Aubin Moutal, Ph.D., assistant professor of pharmacology and physiology.

Gina Yosten, Ph.D., an associate professor of pharmacology and physiology, was awarded an 18-month $162,000 grant from the Foundation of Prader Willi Research titled 鈥淪patial Molecular Imaging of the Human PWS Hypothalamus鈥� (1243623). Working with Grant Kolar, Ph.D., professor of pathology and pharmacology and physiology, this funding will allow for the investigation of spatial molecular profiles of cells of the hypothalamus using tissues from donors with Prader Willi syndrome and matched control donors. The long-term objective of this study is to evaluate how spatially-driven interactions between the different cell types within the hypothalamus might contribute to the pathogenesis and symptomology of Prader Willi syndrome. Ms. Megan Pater, a graduate student in Pharmacology and Physiology, and an expert in spatial molecular imaging, will play an instrumental role in this study.

Yosten was also awarded a one-year $60,156 grant from the Foundation of Prader Willi Research titled 鈥淓valuate Ultrastructure of Hypothalamic Tissues from Mouse and Rat Models of PWS and Human PWS Donors鈥� (1314260). Working with Kolar, this project will investigate how deficiency of the MAGEL2 gene, which exhibits impaired expression in the setting of Prader Willi syndrome, impacts secretory granule structure and function. The long term objective of this study is to determine whether impairments in secretory granule trafficking underly the phenotypes associated with Prader Willi syndrome and other syndromes with MAGEL2 deficiency.