Postdoctoral Scholars
Dominique Baldwin, PhD
Faculty Mentor: Judith Simcox, PhD
Automated LC/MS workflow for the characterization of the inflammation driving lipidome
Inflammaging is the chronic, low-grade inflammation that occurs with age. As such, inflammaging is a critical mediator of various age-related disease, particularly cardiovascular disease (CVD). Initial CVD risk assessment typically includes a lipid panel which characterizes low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and total triglyceride levels in the blood plasma. However, recent research suggests that this lipid panel does not equally predict CVD risk in different populations of patients. Fortunately, the Simcox lab has recently found that plasma arachidonic acid (ARA), which is a precursor to proinflammatory oxylipid species, correlates well with CVD risk. My research focuses on creating a mass spectrometry-based lipidomics workflow to quantify inflammation signaling oxylipids and their precursors that can be used for clinical diagnostic assessment of CVD risk and other inflammaging comorbidities.
Kyle Conniff, PhD
Faculty Mentor: Carey Gleason, PhD
Aging and dementia in Native American communities
As a statistician, I navigate two realms of research: statistical methodology assessment/development and applied-science statistical analyses. My statistical research focuses on assessing assumptions and their impacts on results within the time-to-event modeling framework. Primarily motivated by aging and dementia-related outcomes in observational Indigenous healthcare settings, I explore two main avenues of statistical research:
1. How do intricacies within data collection and structure influence the point estimates and predictive ability of our statistical models?
2. How do implicit assumptions in our modeling choices impact our results, and what are the most robust assumptions against these potential misspecifications?
On the applied science side, I examine factors for Native American research participants that are related to dementia diagnoses, dementia progression, and research participation. This includes social determinants of health, biomarkers, and demographic characteristics. Most of my work is focused on improving the aging health experience of our Native American Elders.
Cassandra McGill, PhD
Faculty Mentor: Rozalyn Anderson, PhD
Identifying molecular changes across tissues in different animal models and humans to define pathways of aging
Aging is the primary risk factor for many chronic diseases, yet the biological mechanisms that drive aging remain incompletely understood. Much of our mechanistic insight has come from short-lived models such as mice, which offer genetic tractability but pose challenges for translation to humans due to differences in physiology, lifespan, and aging trajectories. Rhesus macaques provide a complementary model, as their immune, endocrine, and neurological systems more closely resemble those of humans and allow the study of aging patterns that better reflect human biology.
My research identifies sex-specific molecular changes across tissues in mice, rhesus macaques, and humans to define conserved, sexually dimorphic pathways of aging. Identification of conserved signatures will facilitate in-depth mechanistic discovery in preclinical models, allowing for reverse translation of insights from humans to basic science. In parallel, I evaluate interventions that improve aging phenotypes in mice to determine whether their efficacy and mechanisms differ between males and females, establishing a sex-informed framework for biomarkers and therapeutic targets relevant to human aging.
Isabella Whitworth, PhD
Faculty Mentor: Audrey Gasch, PhD
Investigating the role of translational errors in aneuploidy-induced premature aging
Carrying an additional chromosome, also referred to as aneuploidy, has significant consequences for cellular health. One of the most common phenotypes for the human aneuploidy syndrome Down syndrome is premature aging, but the reasons remain a mystery. Recent work in our lab showed that aneuploidy in yeast cells also causes premature chronological aging, regardless of which chromosome is duplicated. This is caused in part by defects in the Ribosomal Quality Control (RQC) pathway that recognizes and disassembles stalled ribosomes and initiates degradation of polypeptides associated with them. Interestingly, errors in translations are known increase during normal aging for unknown reasons. We hypothesize that translation of extra transcripts from duplicated chromosomes creates stress on the translational system that causes higher rates of translational errors to accelerate aging. My work is testing the hypothesis that aneuploidy accelerates translational decline beyond ribosomal stalling. By characterizing translational errors in euploid and aneuploid cell life cycles, we can better understand how translational fidelity changes throughout normal and accelerated aging.
Predoctoral Scholars
Tina Dang
Faculty Mentor: Lingjun Li, PhD
Advanced Mass Spectrometry Approaches to Elucidate Antimicrobial Peptide Dysregulation in Alzheimer’s Disease
My research centers around antimicrobial peptides (AMPs) which are critical components of the innate immune system that neutralizes pathogens and regulates innate immune signaling. While traditionally studied in the context of host defense, emerging evidence suggests that AMPs also play important roles in neuroinflammation and neurodegenerative diseases. Amyloid beta 1-42 (Aβ 1-42) has been long associated with Alzheimer’s Disease (AD), but has recently been shown to exhibit antimicrobial activity and structure similarity to canonical AMPs. These findings have contributed to the growing support for the Microbial Alzheimer’s Disease (MAD) hypothesis, which proposes that microbes and the dysregulated innate immune response may drive neurodegeneration and AD pathology. I aim to quantify AMP dysregulation in AD using targeted and discovery based mass spectrometry techniques. Using LC-MS/MS to profile AMPs, including LL-37, Aβ 1-42, Lactoferrin, and Defensins, as well as their post-translational modifications. To complement the LC-MS/MS peptidomics data, my work also incorporates mass spectrometry imaging with photocleavable mass tags to enable spatial mapping of AMPs in AD mouse brain tissue and integration with lipidomic analysis to explore AMP-associated lipid oxidation. Collectively, this work integrates advanced mass spectrometry techniques to provide molecular insight into AMP dysregulation in AD and contribute to a better understanding of how innate immune peptides may influence neuroinflammatory pathology.
Nicholas Garcia
Faculty Mentor: Anna Huttenlocher, MD
Aging Immunology: How aging alters neutrophil function and migration
Neutrophils are the most abundant immune cell present in the human body, accounting for 50-70% of immune cells in the body. Neutrophils act as first responders responding to injury and infection and are crucial in host defense. It is known that neutrophil function changes with age. These changes are associated with increased susceptibility to infection, delayed wound healing, and chronic inflammation associated with aging. Specific changes in neutrophil function with age include decreased pathogen clearance, increased reactive oxygen species (ROS) production, altered migration, and chronic neutrophil activation. While it is established that neutrophil function is altered with age, the underlying mechanisms that regulate these changes remain unclear. My research is focused on uncovering these mechanisms leveraging human induced pluripotent stem cell derived neutrophils in tandem with zebrafish. The combination of these two powerful systems will enable unique insight into alterations in neutrophil biology with aging. A better understanding of how neutrophil biology changes with aging will provide insight and can inform future therapeutic intervention to increase healthspan.
Sam Reid
Faculty Mentor: Luigi Puglielli, MD, PhD
Overexpression of COASY effects on downstream acetylation machinery in the ER and aging
The endoplasmic reticulum (ER) is important for maintaining proteostasis in the secretory pathway as well as metabolic crosstalk between different intracellular compartments through the ER acetylation machinery. AT-1 along with SLC25A1 and SLC13A5 maintain the intracellular flux of citrate and acetyl coenzyme A (acetyl-CoA). The COASY protein along with Pantothenic acid produces CoA in the cytosol, which is required for the biosynthesis of acetyl-CoA prior to being transported into the ER by AT-1. Previous models of AT-1 overexpressing mice as well as SLC25A1 and SLC13A5 overexpressing mice have shown behavioral phenotypes as well as metabolic responses suggesting that abnormal flux of acetyl-CoA from the cytosol to the ER could be mechanistically related to behavioral and metabolic differences. To expand on these previous findings, we are looking at the effects of overexpression of the COASY protein in mouse models to elucidate the potential metabolic consequences.
Sam Saghafi
Faculty Mentor: Dawn Davis, MD, PhD
Impact of Dietary Interventions on the Outcomes of Bariatric Surgery
Obesity and Type 2 Diabetes (T2D) are highly prevalent diseases that negatively impact the normal aging process. Bariatric surgery is currently the most effective treatment for both obesity and T2D, with patients experiencing dramatic weight loss and many reaching remission of T2D. However, it is unclear how diet composition after surgery impacts weight loss and improvements to glycemia. My research is focused on assessing how modulating the levels of dietary protein that mice consume after bariatric surgery impacts weight loss, glucose tolerance, insulin sensitivity, and hormone secretion. I am particularly interested in studying how hormone signaling from the intestine to the pancreatic islet change in the context of bariatric surgery, and how this effects insulin secretion.
Nicole Wicker
Faculty Mentor: Snehal Chaudhari, PhD
Using C. elegans to understand microbe-host interactions in aging
It has been known for decades that the community of microbes inhabiting our gut can impact aging. Small molecule metabolites made by the gut microbiome represent the most dominant way our gut bacteria influence us. The mechanisms by which the gut microbiome affects aging are poorly understood. Research in this field is limited by the lack of preclinical models that can allow investigation of individual gut bacteria on molecular mechanisms underlying aging. My research aims to establish Caenorhabditis elegans as a new model organism for studying mammalian host-microbe interactions in aging. Novel high-throughput screening techniques will allow identification of bacterial molecules and host signaling mechanisms that underly microbiome-mediated aging phenotypes. Characterizing these mechanisms will increase our understanding of the biology of aging and will provide therapeutic targets to combat aging-associated diseases.