Current Postdoctoral Trainees
(Faculty Mentor – Rozalyn Anderson)
“RNA-based regulation of gene expression in aging and following caloric restriction.”
My research is focused on how energy metabolism can influence gene expression in different tissues during aging, and in response to aging interventions such as caloric restriction (CR). Specifically, I’m interested in how the transcriptional co-activator PGC1α is regulating alternative splicing and gene expression at the co-transcriptional level in response to shifts in energy metabolism. I’m also interested in the potential role that circulating microRNAs (miRNAs) may play in consequently contributing to a metabolic CR phenotype in animals. Through these lines of investigation, I seek to better understand the molecular mechanisms of aging in the hopes we may be able create nutritional/pharmaceutical therapeutics to mimic a CR phenotype and slow the aging process.
(Faculty Mentors – Barbara Bendlin and Corinne Engelman)
“Unraveling the underlying biology of Alzheimer’s pathology with big-data ‘omics”
The foundation of my research is analysis of genetic associations with quantitative traits, such as disease biomarkers and endophenotypes, to help further our understanding of complex disease. Currently my research integrates genomics, proteomics, metabolomics, and bioinformatics methods to help determine the underlying biology impacting Alzheimer’s disease (AD). By focusing on biological mechanisms rather than clinical diagnosis, my research will not only help in understanding AD pathology but also in understanding disorders that share some of the same biological mechanisms. With greater understanding of the underlying biological mechanisms of disease, we can begin to explore therapeutic targets.
(Faculty Mentor- Dustin Deming)
“Organotypic Cultures to Characterize Heterogenity of Therapeutic Response in Geriatric Oncology”
My research investigates techniques for developing translational tools to advance the practice of precision oncology for geriatric patients with gastrointestinal cancers. The goal of my work is to develop techniques as a correlative biomarker to predict response for an individual patient. Geriatric patients represent 15% of those enrolled in prospective oncology studies while accounting for 70% of cancer-related mortality. Tuning therapies with improved therapeutic activity is necessary to avoid added toxicities from ineffective therapies. This includes prospective investigations of cancer spheroids assessed by change in growth and metabolism from the University of Wisconsin’s Precision Medicine Molecular Tumor Board.
(Faculty Mentor- Wan-Ju Li)
“Optimizing Autologous Mesenchymal Stem Cells: Preparing for the Era of Precision Medicine”
Dr. Walczak, a clinical instructor in the Department of Orthopedics and Rehabilitation, has entered the PhD CI program. He is using nanoparticles and stem cell technologies to develop novel improvements in orthopedic surgery, specifically targeting the mechanisms of aging in mesenchymal stem cells. Dr. Walczak’s background includes degrees in medicine and physical therapy. His mentor is Wan-Ju Li, PhD, Associate Professor of Biomedical Engineering and Orthopedics & Rehabilitation.
Current Predoctoral Trainees
(Faculty Mentor – Darcie Moore)
“The role of nesprin-3 in mammalian neural stem cells”
Hippocampal neural stem cells (NSCs) give rise to new functional neurons throughout life in a process referred to as adult neurogenesis. With increasing age, there is a stark reduction in NSC proliferation, contributing to cognitive flexibility with mechanisms yet unclear. Disruption of the nuclear envelope has been shown to negatively affect NSC proliferation, and may be involved in regulating neurogenesis. My research is focused on characterizing nesprin-3, an outer nuclear envelope protein, in NSCs. Recently we have found that NSCs express a novel, neural-lineage specific variant of nesprin-3. The aim of my work is to characterize this isoform and its protein interactions, and determine the role it may play in NSC maintenance, and hippocampal functioning. These studies will allow us to better understand the physiological processes that govern stem cell proliferation with age.
(Faculty Mentors – Anna Huttenlocher and Nancy Keller)
“Investigating longevity factors as targets of antifungal development”
Aspergillus fumigatus is the primary causative agent of invasive aspergillosis, a devastating fungal disease which primarily affects immunocompromised populations. Canonical regulators of eukaryote longevity such as NAD+ metabolism and sirtuins are conserved in A. fumigatus, however, the role of aging pathways in virulence of this human pathogen remains unknown. The goal of my work is to dissect how metabolic pathways important to longevity drive virulence of A. fumigatus and how those pathways can be targeted to improve antifungal therapies. This work will provide us with a better understanding of the role of aging and metabolism at the host-pathogen interface and allow identification of targetable fungal pathways to treat invasive aspergillosis.
(Faculty Mentor – Roz Anderson)
“Glycogen synthase kinase 3β (GSK-3β) and metabolic dysfunction in age-related neurodegeneration”
My work is characterizing the mechanisms of neuroprotection by caloric restriction (CR), a model of delayed aging. Recently, our lab has established that CR induces a distinct state of energy metabolism in the hippocampus that is associated with reduced levels of GSK-3β, a nutrient-sensitive kinase that is known to participate in neurodegeneration. Additionally, we have demonstrated that GSK-3β negatively regulates the activity and stability of PGC-1a, a critical regulator of energy metabolism. We are now working to directly determine the role of GSK-3β in neuronal energy metabolism both at the cellular level, and in specific regions of the brain that are sensitive to neurodegeneration. This will allow us to better understand the principle factors that underlie age-related cognitive impairment.
(Faculty Mentor – David Pagliarini)
“Defining the biochemical mechanisms of early-stage complex I assembly”
Mitochondria lie at the heart of cellular metabolism, using the oxidative phosphorylation (OXPHOS) system to generate ATP as a cellular energy source. OXPHOS dysfunction has been linked to a wide spectrum of clinical diseases, including disease of aging (e.g. Alzheimer’s disease, type 2 diabetes mellitus). OXPHOS dysfunction is most commonly caused by defects in complex I (CI) of the respiratory chain. While the mature complex has been studied extensively, only a third of CI dysfunctions are due to mutations in its structural subunits. The remaining two thirds are caused by mutations in proteins involved in the assembly and maturation of CI, which are collectively termed “assembly factors (AFs).” To date, 16 AFs have been identified, but the biochemistry underlying their function remains poorly defined. My research interest lies in elucidating the biochemical mechanisms of CI assembly, beginning with the initial stages of assembly. A deeper understanding of this process will advance our knowledge of mitochondrial metabolism as a key player in aging and age-related disease vulnerability.
(Faculty Mentor – David Wassarman)
“The Role of Aging-dependent Metabolic Dysfunction in Traumatic Brain Injury Outcomes”
Traumatic Brain Injury (TBI) is predicted to be the 3rd leading cause of death worldwide by 2020, with 50,000 victims dying each year in the United States and thousands more survivors suffering from long-term disabilities, making it one of the greatest public health burdens in society today. Elderly populations in particular are highly vulnerable to the effects of TBI, resulting in higher rates of mortality, and severe cognitive and emotional deficits in survivors. My work in the Wassarman lab utilizes our Drosophila melanogaster model of TBI to characterize how aging affects the metabolic state of flies immediately following TBI, as well as to elucidate the mechanisms that lead to disrupted energy homeostasis and ultimate TBI outcomes. These studies will provide a better understanding of the critical genes involved in metabolic dysfunction following TBI, establish where the most severe dysregulation is taking place, and identify novel targets for metabolic therapies.