Philip Kramer

Philip Kramer
Wake Forest School of Medicine · Internal Medicine - Gerontology

Ph.D.

About

56
Publications
12,441
Reads
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1,280
Citations
Additional affiliations
August 2010 - July 2015
University of Alabama at Birmingham
Position
  • PhD Student
Education
August 2010 - June 2015
University of Alabama at Birmingham
Field of study
  • Biomedical Science
August 2005 - May 2009
Auburn University in Montgomery
Field of study
  • Medical Technology/Biology

Publications

Publications (56)
Article
Mitochondrial dysfunction underlies the etiology of a broad spectrum of diseases including heart disease, cancer, neurodegenerative diseases, and the general aging process. Therapeutics that restore healthy mitochondrial function hold promise for treatment of these conditions. The synthetic tetrapeptide, elamipretide (SS-31), improves mitochondrial...
Preprint
Full-text available
Mitochondrial dysfunction underlies the etiology of a broad spectrum of diseases including heart disease, cancer, neurodegenerative diseases, and the general aging process. Therapeutics that restore healthy mitochondrial function hold promise for treatment of these conditions. The synthetic tetrapeptide, elamipretide (SS-31), improves mitochondrial...
Article
Full-text available
Dysregulated CD4 T cell responses are causally linked to autoimmune and chronic inflammatory disorders, yet the cellular attributes responsible for maintaining the disease remain poorly understood. Herein, we identify a discrete population of effector CD4 T cells that is able to both sustain and confer intestinal inflammation. This subset of pathog...
Article
Full-text available
Protein S-glutathionylation is an important reversible post-translational modification implicated in redox signaling. Oxidative modifications to protein thiols can alter the activity of metabolic enzymes, transcription factors, kinases, phosphatases, and the function of contractile proteins. However, the extent to which muscle contraction induces o...
Article
Protein S-glutathionylation (P-SSG) is a reversible redox modification known to alter the activity of transcription factors, kinases, and contractile proteins as well as protect critical cysteine residues from irreversible oxidation. Exercise elicits an acute oxidative stress that is reported to result in beneficial adaptive responses, a process kn...
Article
Full-text available
Women living with HIV may present with high levels of body fat that are associated with altered bioenergetic function. Excess body fat may therefore exacerbate the bioenergetic dysfunction observed with HIV infection. To determine if body fat is associated with bioenergetic function in HIV, we conducted a cross-sectional study of 42 women with HIV...
Article
Exercise is the most effective treatment for sarcopenia, the age-related loss of muscle mass and function. Despite its positive effects, many studies indicate that adaptive signaling with exercise is altered or attenuated with age. We and others have found that aging muscle presents with increased mitochondrial reactive oxygen species (ROS) generat...
Article
Full-text available
Metabolic control of cellular function is significant in the context of inflammation-induced metabolic dysregulation in immune cells. Generation of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide are one of the critical events that modulate the immune response in neutrophils. When activated, neutrophil NADPH oxidases consume...
Article
Full-text available
Mitochondrial oxidative stress is a common feature of skeletal myopathies across multiple conditions; however, the mechanism by which it contributes to skeletal muscle dysfunction remains controversial. Oxidative damage to proteins, lipids, and DNA has received the most attention, yet an important role for reversible redox post-translational modifi...
Article
Platelet aggregation is an essential response to tissue injury and is associated with activation of pro-oxidant enzymes, such as cyclooxygenase, and is also a highly energetic process. The two central energetic pathways in the cell, glycolysis and mitochondrial oxidative phosphorylation, are susceptible to damage by reactive lipid species. Interest...
Conference Paper
Stored platelet concentrates have been shown to have decreased quality which could ultimately lead to worsening patient outcomes. This phenomenon termed the platelet storage lesion is characterized by the change in cell morphology, decreased aggregation, an increased glycolytic rate, and decreased mitochondrial function, the mechanisms of which are...
Article
The quality of platelets decreases over storage time, shortening their shelf life and potentially worsening transfusion outcomes. The changes in mitochondrial function associated with platelet storage are poorly defined and to address this we measured platelet bioenergetics in freshly isolated and stored platelets. We demonstrate that the hypotonic...
Article
Full-text available
Monitoring the bioenergetics of leukocytes is now emerging as an important approach in translational research to detect mitochondrial dysfunction in blood or other patient samples. Using the mitochondrial stress test, which involves the sequential addition of mitochondrial inhibitors to adherent leukocytes, we have calculated a single value, the bi...
Article
Activation of the phagocytic NADPH oxidase (NOX-2) in neutrophils is a critical process in the innate immune system and is associated with elevated local concentrations of superoxide, hydrogen peroxide and hypochlorous acid. Under pathological conditions, NOX-2 activity has been implicated in the development of autoimmunity, indicating a role in mo...
Article
Mitochondrial function has long been recognized as central to normal physiology and a contributor to a broad range of pathologies. Much of the early research in mitochondrial biology focused on the mechanisms to generate ATP and characterization of mitochondria from highly energetic tissues such as the heart or liver. More recent studies emphasize...
Article
Full-text available
Platelet thrombus formation includes several integrated processes involving aggregation, secretion of granules, release of arachidonic acid and clot retraction, but it is not clear which metabolic fuels are required to support these events. We hypothesized that there is flexibility in the fuels that can be utilized to serve the energetic and metabo...
Article
Full-text available
The apolipoprotein (apo)A-I mimetic peptide 4F favors the differentiation of human monocytes to an alternatively-activated M2 phenotype. The goal of the current study was to test whether the 4F-mediated differentiation of monocyte-derived macrophages (MDMs) requires the induction of an oxidative metabolic program. 4F treatment induced several genes...
Chapter
Macrophages are a versatile and heterogeneous group of cells which vary in phenotype and function. M1-polarized macrophages play a key role in the host defense response via the production of inflammatory mediators and cytokines. The concept of macrophage plasticity proposes that these cells can be reprogrammed to an alternatively activated, M2-pola...
Article
Full-text available
Atherosclerosis and valvular heart disease often require treatment with corrective surgery to prevent future myocardial infarction, ischemic heart disease, and heart failure. Mechanisms underlying the development of the associated complications of surgery are multifactorial and have been linked to inflammation and oxidative stress, classically as m...
Article
Full-text available
Bioenergetics has become central to our understanding of pathological mechanisms, the development of new therapeutic strategies and as a biomarker for disease progression in neurodegeneration, diabetes, cancer and cardiovascular disease. A key concept is that the mitochondrion can act as the 'canary in the coal mine' by serving as an early warning...
Article
Bioenergetics has become central to our understanding of pathological mechanisms, the development of new therapeutic strategies and as a biomarker for disease progression in neurodegeneration, diabetes, cancer and cardiovascular disease. A key concept is that the mitochondrion can act as the 'canary in the coal mine' by serving as an early warning...
Article
Full-text available
Mitochondrial dysfunction is known to play a significant role in a number of pathological conditions such as atherosclerosis, diabetes, septic shock, and neurodegenerative diseases but assessing changes in bioenergetic function in patients is challenging. Although diseases such as diabetes or atherosclerosis present clinically with specific organ i...
Article
Full-text available
The assessment of metabolic function in cells isolated from human blood for treatment and diagnosis of disease is a new and important area of translational research. It is now becoming clear that a broad range of pathologies which present clinically with symptoms predominantly in one organ, such as the brain or kidney, also modulate mitochondrial e...
Conference Paper
Oxidative stress and the formation of reactive oxygen, nitrogen and lipid species (ROS/RNS/RLS) have been attributed to the increased development of complications arising post cardiovascular surgery. Markers of oxidative stress such as cell-free hemoglobin and the presence of F2-isoprostanse have been found in the pericardial fluid (PCF) within fou...
Article
Full-text available
Peripheral blood mononuclear cells and platelets have long been recognized as having the potential to act as sensitive markers for mitochondrial dysfunction in a broad range of pathological conditions. However, the bioenergetic function of these cells has not been examined from the same donors, yet this is important for the selection of cell types...
Article
Full-text available
Objective Many different genes or mediators have been implicated in promoting the development of vasculitis, although little is known regarding the mechanisms that normally act to suppress lesion formation. Endothelial nitric oxide synthase (eNOS) has been shown to inhibit vascular inflammation in many different model systems, but its roles in the...
Conference Paper
Postoperative complications following cardiac surgery significantly increase morbidity and mortality. However, the precise mechanisms involving cardiac dysfunction following cardiothoracic surgery are not clear but are thought to involve oxidative stress. We have made a novel observation that following cardiothoracic surgery, the pericardial fluid...
Article
Oxidative modifications to cellular proteins are critical in mediating redox-sensitive processes such as autophagy, the antioxidant response, and apoptosis. The proteins that become modified by reactive species are often compartmentalized to specific organelles or regions of the cell. Here, we detail protocols for identifying the subcellular protei...

Projects

Project (1)