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Cardiac response to overload states; myocardial hypertrophy and failure, myocardial energy metabolism; coronary vascular response to ischemia.
Metabolic control and regulation in adipocytes, obesity/insulin action, lipid metabolism, protein-lipid association, lipid oxidation, proteomics.
Research in the Bernlohr laboratory focuses on the integration of metabolic regulation, lipid metabolism, gene expression and systems biology towards an understanding of obesity-linked diseases such as Type 2 diabetes, cardiovascular disease and hypertension.
The work focuses on three major projects:
Using a combination of in-vitro and in-situ studies, coupled with RNAi-based knockdown strategies we have demonstrated which cellular proteins facilitate fatty acid flux into and out of adipocytes and how hormones such as insulin and glucagon can regulate such flux.
Dr. Peter Bitterman:
bitte001@umn.edu
Research Interests: Translational Control of Cell Fate
Our research program seeks to understand how the activity state of the protein synthesis apparatus regulates cell function. We have discovered that pathological activation of translation initiation complex eIF4F imparts primary fibroblasts and epithelial cells with autonomy for growth and survival and is required for cancer cells to maintain a malignant phenotype. In contrast, inhibition of eIF4F function activates apoptosis in these cells without harming normal cells. Our research program addresses 3 major questions:
Our investigations feature a dynamic collaborative network of biochemists, cancer biologists, lung biologists and medicinal chemists. Graduate students and post-doctoral fellows will interact with a diverse group of trainees as part of our NIH-sponsored training grant; joining a cohort spanning an educational continuum beginning with honors undergraduates satisfying their research requirement, MD and MD/PhD students, through post-doctoral fellows.
Neuroendocrinology of stress.
The focus of the laboratory is to delineate neuroendocrine mechanisms for the control of adrenal secretion of glucocorticoids, the major output of the hypothalamic-pituitary-adrenal (HPA) axis. One goal is to define the role of adrenal innervation on the control of glucocorticoid secretion. The secretion of the adrenal cortex is dependent on the pituitary hormone, ACTH. Our work has shown that autonomic neural activity contributes to circadian and stress-induced corticosteroid secretion by modulating steroidogenic responses to ACTH, but the central and peripheral neural pathways involved have not been delineated.
To characterize the central neural substrate for circadian changes in glucocorticoids, a combination of a physiological and neuroanatomical methods are employed; plasma ACTH, vasopressin and adrenal steroids are measured and double-label immunohistochemistry and retrograde labeling are used to define the phenotype of neurons activated as a function of time of day. The hypothesis to be tested is that neurons in the paraventricular nucleus (PVN) of the hypothalamus receive input from the suprachiasmatic nucleus (SCN) and project to the spinal cord to provide inhibitory and excitatory input to the adrenal cortex that drives the circadian rhythm.
Other studies are determining the central and peripheral mechanisms that control rapid decreases in glucocorticoids. By active removal of a stressor, rehydration after water restriction or feeding after food restriction are viewed as unique models for assessing processes invoked to reduce stress as reflected by decreases in HPA activity. Using Fos immunohistochemistry coupled with phenotypic labeling, our studies have identified a unique pattern of neural activity in the PVN induced by drinking after repeated water restriction that is not observed after a single episode of water deprivation. Experiments will incorporate microdialysis with CE-LIF detection to determine neurotransmitters released in the PVN that mediate changes in neural and endocrine responses. The goal of this work is to identify central neural circuits controlling HPA activity that could be mobilized to reduce the deleterious effects of stress.
Practice Philosophy
"My philosophy is to provide outstanding and comprehensive care to patients with cardiovascular disease. The therapies for heart disease, offered to my patients, include a number of emerging technologies that are available at the University of Minnesota Medical Center, Fairview. I believe these state-of-the-art therapies also include effective communication, compassion, and a working partnership that collectively result in a high quality of life for my patients."
Specialties
Clinical: Heart Failure and Cardiac Transplantation
Research: Regenerative Medicine, Cardiogenesis, Stem Cell Biology.
I consider learning to be a highly individualized process for which my role as a teacher is to assist individuals to identify the modes of learning which work best for them. In fact, my advice to teaching assistants with whom I have worked is to be as creative in their teaching style as possible. By striving to find new creative angles to present information, a natural result is enhanced learning and perceived excitement for the topic. I personally have enjoyed the advances in computer technology that have allowed for dynamic Powerpoint presentations into which I can easily incorporate video clips.
It has been my good fortune to witness over 50 graduate students complete their degrees while working in my laboratory. Currently, there are 5 doctoral students and 6 masters students working on their research projects in my lab. Yes, it does take much time and effort to train such a group of students, but the mentoring adventure is what, in part, motivates me to continue searching for funding for my research. Additionally, I have been fortunate to have high degrees of camaraderie amongst the students in my lab, hence they play a large role in training each other. More importantly, the way I look at it, I have come to make many good friends while students have worked with me on my research interests.
Dr. Low's research is focused on the use of stem cells for the treatment of neurological disorders such as Parkinson's disease. Research in the area of cell therapy involves the use of neural transplants to repair neural connections in neurodegenerative disorders such as Parkinson's disease.
Research Interests:
Investigations in my laboratory have focused on understanding mechanisms and regulation of electrolyte transport across epithelial tissues and regulation of eosinophil activation in patients with asthma. Cultured human airway epithelial cells and endometrial epithelial cells are currently used to study regulation of ion transport function and cell migration by a variety of signaling molecules. A combination of electrophysiological approaches and molecular techniques provide a means to identify transport mechanisms and signaling pathways that are important in controlling electrolyte and fluid transport across these epithelia. Studies of eosinophil activation conducted in collaboration with Dr. Hirohito Kita from the Mayo Clinic address the mechanism of granule acidification required for granule protein dissolution and the signaling pathways that regulate this process.
Research in my laboratory is directed towards gaining an integrative understanding of the role of the central nervous system in the long-term regulation of arterial pressure and the pathogenesis of hypertension. At the present time we are investigating how circulating hormones, such as angiotensin II and aldosterone, are monitored by specialized sites within the brain called circumventricular organs. We are investigating how these regions influence ongoing sympathetic nerve discharge and ultimately the regulation of arterial pressure. Our long-term goal is to understand, in a quantitative way, the role of such hormonal-sympathetic interactions in normal physiology and the pathophysiology of hypertension. Specifically, we are studying how such interactions are influenced by alterations in dietary salt in hopes of understanding the neurogenic basis of salt-dependent hypertension. A variety of experimental approaches are employed to address these issues including state-of-the-art long-term monitoring of cardiovascular hemodynamics and application of cellular/molecular neurobiological techniques. We have also initiated a collaborative project with the Department of Mathematics to begin developing new mathematical models of how the nervous system regulates cardiovascular function over long periods of time.
In addition to the work in my own laboratory, I am the coordinator for a newly formed national research effort to study the role of the brain in cardiovascular diseases. “The Neurogenic Cardiovascular Diseases Consortium” is a novel NIH funded project which joins 5 major research Universities to investigate neurogenic cardiovascular diseases at all levels of regulation; gene, single cell, neural networks and whole animal. This work will be carried out by Universities of Minnesota (home institution), Pittsburgh, Texas-San Antonio, Florida-Gainesville and Michigan State University.
As the Medtronic-Bakken Chair in Cardiac Repair and the Director of the Center for Cardiovascular Repair, Dr. Taylor blends research using stem cells, genes, and devices to develop novel cardiac and vascular technologies--ones to prevent, treat, and hopefully one day, cure heart ailments. She is involved in both laboratory and clinical studies using cell therapy to treat disease.
Teaching Responsibilities: Theory of Therapeutic Exercise; Biology of Aging, Exercise Physiology of the Elderly.
Special interests: Geriatric Rehabilitation, Aging Skeletal Muscle, Exercise and Inactivity
Other interests: Skeletal Muscle Physiology, Functional Assessment, Congestive Heart Failure
Project 1:
Following myocardial infarction, a prolonged period of LV remodeling with hemodynamic stability may be followed by the development of congestive heart failure (CHF). Hearts with stable remodeling or CHF have many abnormal bioenergetic characteristics, but whether limitations in the ATP synthetic or transport processes actually contribute to the transition from hemodynamic stability to CHF is unclear. Using 4.7 and 9.4 Tesla large bore magnets, the research program has been using porcine models of cardiac hypertrophy (pressure overload or postinfarction LV remodeling) in which a significant portion of the animals develop CHF.
The objectives are to: 1) use new techniques to define the rate limiting step(s) in the ATP synthesis/utilization processes that ultimately restrict maximal contractile performance and myocardial oxygen consumption (MVO2) in either normal or failing hearts; 2)examine in vivo spatially localized (from peri-scar to remote area, and from inner layer to outer layers of the left ventricle) myocardial high energy phosphates, ventricular contractile performance, blood flow, myoglobin saturation, and MVO2 under basal and maximal cardiac workstates in pigs with postinfarction LV remodeling, and during the transition from compensated hypertrophy to heart failure. The results of these experiments may lead to better preventive, diagnostic and therapeutic modalities for heart failure.
Project 2:
The Molecular Lab is located at the Cardiology Division and its goal is to further our understanding of the molecular details of energy metabolism related abnormal expression of genes and proteins in hearts with CHF. These gene and protein expression measurements in combination with the whole animal physiology and myocardial energetics profile measured earlier from the same animal, provide a unique integrated examination of the relationships between gene/protein expression level, myocardial energetics and systemic hemodynamics under the different cardiac workstates, and at the different phases of LV dysfunction. These studies aim to delineate the molecular and cellular details of myocardial dysfunction and to improve our understanding of the basic mechanisms of bioenergetics in failing heart, and hence would be expected to result in improved clinical care of the patients.
Project 3:
The Stem Cell Lab is located at cardiology division. Its goal is to use autologous bone marrow stem cells transplantation andhigh field NMR to follow cellular trafficking in stem cell therapy for myocardial repair. Following myocardial infarction, a prolonged period of LV remodeling with hemodynamic stability may be followed by the development of congestive heart failure (CHF). The recent reports indicate that myocardial environment of hearts with stable postinfarction LV remodeling is permissive to stem cells homing and differentiation. However, the mechanisms of which are not known and the reported beneficial effects of stem cell transplantation remain controversial.