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.
Jason Moody, PhD
Faculty Mentor – Barbara Bendlin, PhD
“Improving early detection, staging neurodegeneration, and identifying risk factors along the biological and clinical Alzheimer’s disease continuum”
My research uses quantitative magnetic resonance imaging (MRI) techniques to detect and stage neurodegenerative, microstructural brain changes along the biological and clinical Alzheimer’s disease (AD) continuum. Using markers of microstructural neurodegeneration derived from various diffusion-weighted MRI (DWI) models, I am currently assessing the relationships between changes in brain tissue microstructure, age, cerebrospinal fluid markers of AD pathology, and AD clinical status in hundreds of aging adults. I am particularly interested in the potential for novel DWI metrics to be able to detect the earliest manifestations of pathological brain alterations associated with AD (years before the onset of clinical symptoms) as well as differentiate between distinct stages of AD, including mild cognitive impairment (MCI) and AD clinical syndrome. I am also interested in using these DWI techniques to identify genetic, environmental, and acquired risk factors for AD dementia, with a current focus on examining the relationships between metabolites impacted by the gut microbiome and brain alterations associated with AD.
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.
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 – Andrea Galmozzi, PhD
“Adipose tissue dysfunction in aging”
Adipose tissue is a central mediator of physiologic metabolism and is implicated in the development of age-associated metabolic disorders. Adipose tissue dysfunction increases with age and often underlies the development of obesity, insulin resistance and type II diabetes (T2D). A prominent feature of aging is the loss of brown adipose tissue (BAT) depots, which are uniquely thermogenic and serve as a metabolic sink via mitochondrial uncoupling. Activation of BAT increases metabolic rate and has been demonstrated to increase energy expenditure in humans. Furthermore, the density of BAT and “beiging” (i.e. the emergence of brown-like adipocytes) in WAT depots is associated with improved metabolic function. My research focuses on identifying adipocyte-intrinsic metabolic and signaling processes that govern the adoption and maintenance of thermogenic machinery, and how these processes change during aging and in metabolic disease development. Identification of pathways regulating adipocyte function and stress responses may reveal new avenues for therapeutic intervention and lead to a novel class of anti-obesity therapies.
Faculty Mentor – Sean Palecek, PhD
“Multi-omic profiling of human pluripotent stem cell-derived cardiomyocytes matured through extended culture”
Heart disease is the leading cause of death in the United States and across the world. This is in part because the cardiomyocytes of the adult human heart have very little capacity for regeneration across the lifespan in times of good health or disease. Human pluripotent stem cell-derived cardiomyocytes offer an ideal source of cardiomyocytes to restore damaged heart tissue through cell therapy; however, stem cell derived-cardiomyocytes remain relatively immature in culture leading to engraftment arrhythmias and limiting their therapeutic potential. My project involves studying the maturation of stem cell-derived cardiomyocytes in vitro through extended culture. Thus far, we have generated metabolomics, proteomics, and transcriptomics data out to 200 days in culture. Currently, we are employing multi-omic data integration to identify novel pathways and markers of cardiomyocyte maturation and aging in vitro. Through improved differentiation and maturation, stem cell-derived cardiomyocytes will serve as a better source of cardiomyocytes for modeling diseases of the aging heart, drug toxicity and discovery, as well as cellular therapy.
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.