1. Cellular Mechanisms of Neuronal Loss in the Hippocampus
The hippocampus is a central structure in the brain and has a major role in learning and memory. Hippocampal damage caused by stroke, aging, or neurodegenerative diseases like Alzheimer’s is associated with cognitive impairment. We investigate molecular mechanisms of hippocampal damage and develop strategies to improve hippocampus-dependent cognitive functions using genetic, pharmacological, and nutritional interventions.
4VO-induced global ischemia causes loss of CA1 hippocampal neurons in rats. NeuN positive CA1 hipocampal neurons are decreased at 7 days post-4VO in rats. A, Sharm. B, 4VO.
2. Mechanisms of Bcl-xL Depletion or ΔN-Bcl-xL Accumulation during Pathological Processes in the Brain
B-cell lymphoma-extra large (Bcl-xL) is a anti-apoptotic protein localized to mitochondria. Bcl-xL improves neuronal ATP production supporting neurite outgrowth and neuronal survival. In contrast to its protective role, Bcl-xL also plays a major role in neuronal death when Bcl-xL undergoes caspase 3-dependent N-terminal cleavage to form ΔN-Bcl-xL. We investigate molecular mechanisms of ΔN-Bcl-xL/Bcl-xL balance (e.g. Bcl-xL depletion and ΔN-Bcl-xL accumulation) during pathological processes in the brain such as cerebral stroke, aging, and neurodegenerative diseases.
Supported by Mary A. Crenshaw Research Fund (01/01/2020-5/31/2021)
Park et al. NRR 2021. See details
3. Mechanisms of Mitochondrial Recruitment during Normal Physiology and During Recovery after Neurotoxic Stimulation
Neurite extension and synapse formation require abundant ATP. Therefore, maintaining a healthy population of mitochondria, the ATP producing organelle of the cell, at the growing sites of neurites is critical to preventing neuronal loss during stroke, aging, and neurodegenerative disease. We study mechanisms of mitochondrial docking, distribution, and mobility (Figure 3). We also investigate mitochondrial availability and neurite outgrowth during normal development and during recovery after brain injury.
Supported by the Scientific Research Honor Society (01/01/2021-12/31/2021)
Movement of mitoRED labeled- mitochondria in hippocampal neurites.
4. Neuroprotective Functions of Dietary Antioxidants
The approaches used to date to experimentally prevent neuronal damage or to promote neuronal survival have limitations (e.g. safety and availability) in translation to human subjects. Therefore, we investigate readily-applicable strategies to protect the human brain. We test whether nutrients, food-based compounds with minimal side effects, are capable of regulating activity of target proteins by 1) direct binding, 2) epigenetic control of transcription and translation, 3) intervening on neuronal death signaling pathways. The ultimate goal of this project is to determine whether nutritional intervention can delay neuronal death and promote rehabilitation of the brain.
Supported by Research Grants Committee (05/15/2018-12/31/2020)
Model of ΔN-Bcl-xL-vitamin E complex.
Docking of α-TCT (grey) to the crystal structure of ΔN-Bcl-xL. Park et al. IJMS 2019. See details
5. Lifestyle Factors Influencing Covid-19 Severity
Coronavirus disease 2019 (Covid-19) is a highly infectious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity of Covid-19 symptoms varies by individual. However, there is a knowledge gap understanding the variables that affect the spectrum of Covid-19 symptoms displayed by young and relatively healthy individuals. Our team investigate if lifestyle factors such as vaccination history, diet, and outdoor activity influence the severity of Covid-19 in otherwise healthy young adults. Media
6. Mitochondrial Dysfunction during Breast Cancer Metastasis
Circulating tumor cells (CTCs) are cells which have detached from the primary tumor and circulate through the bloodstream. Survival of CTCs at a secondary location is an early step in metastatic progression of cancer. We investigate mechanisms of alteration of mitochondrial energy production, mitochondria-mediated death mechanisms, and mitochondrial distribution in circulating breast cancer cells.
Supported by Alabama Life Research Institute (01/01/2020-06/30/2021)
7. Epigenetic Influences of Prenatal Dietary Nitrate on Nutritional Programming of Brown Adipose Tissue Differentiation and Cardiometabolic Outcomes in Offspring of Obese Sprague-Dawley Rats
To test if maternal obesity influences adipose tissue differentiation and cardiometabolic outcomes of offspring, and if prenatal intake of dietary nitrates reverses metabolic perturbations on offspring.
Supported by Academy of Nutrition and Dietetics (11/01/2020-10/31/2022)