Current Trainees

Current Postdoctoral Trainees

Josef Clark
(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.

Mark Farrugia photoMark Farrugia
(Faculty Mentor - Luigi Puglielli)
"Structural characterization and inhibition of the endoplasmic reticulum protein acetylation machinery for the purpose of ameliorating or preventing Alzheimer’s disease."
My work is focused on exploring the components of the endoplasmic reticulum acetylation machinery, namely the acetyl-CoA transporter, AT1, and the acetyltransferases, ATase1 and ATase2. In brief, my aim is to better determine the structures of these components to develop specific inhibitors for the acetyltransferases, inhibition which has been shown to halt the development of Alzheimer’s disease in a mouse model system. The main goal of this work is to determine the regulation network for endoplasmic reticulum protein acetylation and use this knowledge to allow us to better understand and control the progression of several age-related degenerative diseases.

David KosoffDavid Kosoff
(Faculty Mentor- Joshua Lang)
"Age-related loss of immune function promotes the development and progression of cancer in the elderly"
Dr. Kosoff’s project will focus on age-related immune dysfunction and how this relates to prostate cancer. Through the use of novel microfluidic platforms, he will seek to analyze the functional relationship between immune and prostate cancer cells in co-culture. He will attempt to further delineate the mechanisms behind age-related loss of immune function and how this may be mediated by epigenetic alterations that accumulate with age.  Additionally, he aims to evaluate immune targeted therapies for treatment of prostate cancer as well as the ability of epigenetic modulators to enhance the effectiveness of such agents.

Joshua RothJoshua Roth
(Faculty Mentor- Darryl Thelen)
"Optimal Patient-Specific Treatments for Osteoarthritis"
Symptomatic osteoarthritic is a debilitating disease that causes pain, stiffness, and loss of knee function. Symptomatic osteoarthritis of the knee occurs in 10% of men and 14% of women aged 60 years or older, and the prevalence is expected to increase with the aging population. Treatments for osteoarthritis range from non-invasive interventions (e.g., braces and shoe inserts) to invasive interventions (e.g., osteotomy and total knee replacement). The aim of my research is to investigate how both biomechanical and biological factors affect the outcome of different treatment options in these older adults. A better understanding of these factors should enable clinicians to identify the optimal treatment for an individual patient that best restores normal knee function and keeps these patients active.

 

Current Predoctoral Trainees

Nicole Cummings
(Faculty Mentor - Dudley Lamming)
"The role of branched chain amino acids in metabolic health and longevity"

My work in the Lamming lab focuses on the metabolism of the branched chain amino acids (BCAAs; leucine, isoleucine, and valine). The lab found previously that restriction of dietary BCAAs reduces adiposity and improves glycemic control. We are now working to determine if restricting BCAAs can promote healthy aging and possibly extend the lifespan of several mouse models of accelerated aging. In addition, we are working on determining the mechanism by which BCAA restriction supports a healthy metabolism.

Inca DieterichInca Dieterich
(Faculty Mentor - Luigi Puglielli)
"AT-1: A critical regulator of intracellular crosstalk that ensures cellular homeostasis"

My work in Dr. Luigi Puglielli’s lab addresses questions of the aging brain at a biochemical and molecular level. Specifically: how do intracellular organelles communicate between each other to maintain cell homeostasis?  The secretory pathway is a quality control system in the cell and is responsible for acetylating nascent polypeptides in the Endoplasmic Reticulum.  AcetylCoA is the donor for aforementioned acetylation events. AT-1 is the ER membrane transporter which translocates AcetylCoA from the cytosol into the ER.  Changes in AT-1 activity are rapidly sensed by the nucleus, where it causes epigenetic changes, the mitochondria, where it causes metabolic changes, and the cytosol, where it causes changes in lipid metabolism. Therefore, AT-1 is emerging as a central novel regulator of intracellular and metabolic cross-talk linking together different cell organelles and metabolic pathways. I aim to understand the specific biochemical and molecular mechanisms that ensure this cross-talk, which are currently unknown. 

Kyle Robinson

Kyle Robinson
(Faculty Mentor - David Pagliarini )
"Systematic functional annotation of mitochondrial proteins: missing steps in Coenzyme Q biosynthesis"

Mitochondria are central to cellular metabolism and fundamentally connected to aging and age-related disorders, and yet ~20% of mitochondrial proteins remain uncharacterized. Because of this knowledge gap, many mitochondrial processes are incompletely understood. One example is the biosynthesis of Coenzyme Q (CoQ), a critically important lipid that is present in all living cells. CoQ was discovered here at UW-Madison about sixty years ago, but multiple steps in its biosynthesis pathway are still unknown. Mitochondrial CoQ levels naturally decline as humans age, and it is believed that the resulting effects on electron transport and/or oxidative stress could underlie many aging-related pathologies. To this end, Kyle’s research focuses on identifying the proteins involved in the endogenous production of CoQ and characterizing their functions.

Dylan SouderDylan Souder
(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.

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