Current Postdoctoral Scholars
Kyle Edmunds, PhD
Faculty Mentor – Ozioma Okonkwo, PhD
“Brain-derived neurotrophic factor, cardiorespiratory fitness, and sleep in preclinical Alzheimer’s disease”
Emerging evidence on the risk and resilience factors in preclinical Alzheimer’s disease (AD) points to the hypotheses that: (1) the Val66Met polymorphism in the gene for brain-derived neurotrophic factor (BDNF) adversely impacts both cognitive trajectory and β-amyloid burden, and this relationship is mediated by circulating BDNF expression; and (2) cardiorespiratory fitness (CRF) and sleep moderate the relationship between BNDF genotype and AD biomarkers. My research aims to test these hypotheses by assembling linear mixed models from longitudinal data on cognitive decline, AD neuroimaging/circulating biomarkers, BDNF genotype/plasma levels, CRF measures, and sleep quality. Altogether, this project will provide new knowledge on the mechanistic role of BDNF in preclinical AD and whether the deleterious impacts of the Val66Met polymorphism or differences in BDNF expression can be modified by CRF and sleep as malleable lifestyle factors.
Keith Knurr, DPT, SCS
Faculty Mentor – Bryan Heiderscheit, PT, PhD, FAPTA
“The impact of knee joint injuries during sport on long-term health outcomes in former collegiate athletes”
An anterior cruciate ligament (ACL) injury is devastating, not because of the initial trauma, but rather the ensuing cascade of biological processes that impairs mobility as a person ages. Around 50% of individuals that suffer an ACL injury show signs of osteoarthritis within 10 years and many go on to a total knee arthroplasty at an earlier age than the general population. Factors that influence the onset and progression of osteoarthritis and overall health outcomes later in life are poorly understood in this population. My research aims to 1) elucidate the influence age has on the differences in physical activity levels, quality of life, knee function, and mental health outcomes between former collegiate athletes that sustained an ACL injury and those that did not; and 2) determine the association between knee cartilage loading patterns during walking and running and knee cartilage health in former collegiate athletes that underwent ACL-reconstruction (3-15 years post-operatively). Findings will lay the ground work for a large scale longitudinal cohort and intervention-based trials aimed at mitigating the onset and progression of osteoarthritis in individuals with previous knee injuries.
Ryan Sprenger, PhD
Faculty Mentors – Tracy Baker, PhD & Jyoti Watters, PhD
“Neuronal degeneration of respiratory related brainstem networks in Alzheimer’s Disease”
The focus of my research is primarily on respiratory function in challenging situations, including in aging and age-related diseases. Significant respiratory decline is commonly observed in Alzheimer’s disease (AD) patients, and this respiratory decline may be rooted in respiratory related brainstem networks affected by AD progression. Further, hypoxic damage is suspected to contribute to hastened AD progression, yet the nature of how hypoxia is produced in AD is unclear. Most AD patients experience insufficient ventilation during sleep, as well as sleep apnea episodes, both of which would cause hypoxia and thus potential hypoxia related damage. However, it is not known why these disrupted sleep phenotypes develop. One candidate is loss of chemoreceptor function due to AD progression, and most chemoreceptors are located in the pontine and medullary regions of the brainstem. Thus, investigating neuronal changes in these regions may shed light on respiratory decline in AD as well as aging.
Yang Yeh, PhD
Faculty Mentor – Dudley Lamming, PhD
“Selective protein restriction as a late-life dietary intervention for healthspan, lifespan, and senescence”
I am interested in dissecting the biological mechanisms of aging in order to identify novel life-extending therapeutics. Caloric restriction (CR) remains the most robust mean of improving longevity but its compliance is difficult in humans. The dietary reduction of branch chained amino acids (BCAAs), especially isoleucine (Ile), confers many benefits of CR when fed lifelong. My research will evaluate whether the BCAA- or the Ile-restricted diets can serve as a late-life intervention in aged animals. Further, recent advances with senolytic drugs have entered the clinical stage as a new wave of life-extending treatments with potential benefits in improve dementia symptoms. My work will also evaluate whether the effects of protein-restriction share any common mechanisms with these anti-senescent drugs.
Current Predoctoral Scholars
Faculty Mentor – Miriam Shelef, MD, PhD
“Rheumatoid factor in rheumatoid arthritis and inflammaging”
Rheumatoid arthritis (RA) is a chronic, inflammatory disorder involving pain, stiffness and swelling of the synovial joints that can lead to decreased performance in activities of daily living and decreased productivity in the aging population. Most patients with RA have rheumatoid factor (RF), antibodies against the Fc portion of IgG. RF positivity is a poor prognostic marker in patients with elderly onset RA, underlining a potential pathologic role. My project involves identifying novel sites of binding by RF, which may provide insight into the currently unknown pathology of rheumatoid arthritis. Further, by evaluating RF reactivity in rheumatoid arthritis and control subjects, we will support the development of improved RF-based diagnostic tests. This will benefit the aging population as rheumatoid arthritis is among the most common inflammatory diseases in older age groups. The inflammatory pathway in rheumatoid arthritis may also provide insights into inflammation in other autoimmune and infectious diseases.
Faculty Mentor – Lingjun Li, PhD
“Mass Spectrometry-Based Metabolomics for Alzheimer’s Disease Biomarker Discovery”
Alzheimer’s Disease (AD) is the sixth leading cause of death in the United States and is the most common cause of dementia in the aging population. In order to diagnose AD prior to cognitive symptom onset, the complete metabolome and lipidome of AD must be well-characterized, and there is a need to develop better technology to allow for detection of early AD markers with greater sensitivity and accuracy. Typically, AD metabolomic studies utilize brain tissue, cerebrospinal fluid (CSF), plasma, and serum as tissue sources, but my research focuses on erythrocytes, or red blood cells. Erythrocytes are an overlooked component of blood and are a valuable source of disease biomarkers, as erythrocytes are active metabolic cells with intact biochemical pathways that are maintained throughout the cell’s lifespan. Because of this, any changes in red blood cell metabolite concentrations in AD patients could be indicative of systemic metabolic dysfunction, which could give insight into the systematic progression of AD. In my research, I use mass spectrometry to detect and quantify metabolites and lipids in AD erythrocytes.
Faculty Mentor – Adam Konopka, PhD
“The role of mTOR in age-related osteoarthritis.”
Osteoarthritis (OA) is a degenerative joint disease which disproportionately affects older adults. There are currently no disease modifying therapies for OA, due in part to (1) our incomplete understanding of the mechanisms involved in the onset and progression of OA and (2) the lack of appropriate models to study age-related OA and translate findings from rodent models to humans. My research uses a translational approach to address these gaps in the field and understand the contribution of the mechanistic target of rapamycin (mTOR) pathway to OA pathogenesis. Using chondrocyte culture and transgenic mouse models, we are dissecting the effect of each signaling branch of the mTOR pathway and its downstream effectors on OA. We also analyze primary human tissue and have characterized the common marmoset as novel, non-human primate model of OA to understand translational potential and clinical relevance of our mechanistic findings.
Taylor Schoen, MS
Faculty Mentors – Anna Huttenlocher, MD and Nancy Keller, PhD
“Lipid modulators of inflammation and wound healing”
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 – James Keck, PhD
“Impact of respiratory chain complex I assembly on mitochondrial function”
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.