Project Investigators/Mentors
Current Project Investigators/Mentors
- Use of C. elegans as a model to study the LAT gene of human herpesvirus type 1 - Dr. Ana Bratanich
- A Novel Genetic Approach for Elucidating Glycopeptide Hormone Functions - Dr. David S. Fay
- A Natural Model for the Study of Chronic and Acute Renal Failure - Dr. Henry J. Harlow
- Development of an Animal Model for Exploring Postpartum Depression - Dr. Gail Leedy
- Lineage-specific Processes of Evolution - Dr. David Liberles
- Respiratory, laryngeal, and oromandibular coordination - Dr. Roger W. Steeve, David L. Jones
- Lifestyle Interventions Targeting Global Vascular Health and Risk Factor Management - Dr. Derek T. Smith, Dr. Clarann L. Weinert
- Amino Acid Infusion on mTOR Signaling in Fetal Muscle under Nutrient Deficiency - Dr. Min Du, Dr. Stephen P. Ford
- Aberrant Integration of Mitochondrial Functions in Human Choreoacanthocytosis - Dr. Peter Thorsness
- Role of Cohesion in Apoptotic Cell Death - Zhaojie Zhang
- Vitamin E, Ovarian Cancer and Fertility - Dr. William Murdoch
- Maternal Undernutrition and its Effects on Fetal Heart Gene Expression - Dr. Hyung Chul Han
Past Project Investigators/Mentors
- Maternal Undernutrition and its Effects on Fetal Heart Gene Expression - Dr. Hyung Chul Han, Dr. Thomas R. Hansen
- Identification of Signal Pathways Involved in Transmitter-mediated Vasopressin Release - Dr. Francis W. Flynn
- Placentomal Vascular Adaptations to Early maternal Nutrient Restriction in the Ewe - Dr. Meijun Zhu, Dr. Stephen P. Ford
- Developing Capacity for Community-Focused Health Research - Dr. Sharon A. Cumbie, Dr. Clarann L. Weinert
Current Project Investigators/Mentors
Use of C. elegans as a model to study the LAT gene of human herpesvirus type 1 - Dr. Ana Bratanich- Top
Dr. Ana Bratanich, Assistant Professor, Veterinary Sciences
Use of C. elegans as a model to study the LAT gene of human herpesvirus type 1
C. elegans will be used as a model to study the anti-apoptotic abilities of the LAT gene of human herpesvirus type 1. Recently, it has been shown that the LAT gene encodes a microRNA which may play a key role the anti-apoptotic effects observed in vitro. Transgenic strains of this worm will be created that express the entire LAT gene as well as the region encoding the microRNA. Expression of these sequences will be achieved using a promoter that is activated in many cell types during early stages of development. A mutant C elegans strain with a defect in apoptotic body removal will be used to create these transgenic strains to facilitate the visualization of cell changes. Transgenic worms will be evaluated phenotypically to establish if the normal cell fate has been altered during expression of any of the LAT sequences. If cell death is prevented, these findings will provide the basis of future experiments to dissect the cellular factors involved in that inhibition.
A Novel Genetic Approach for Elucidating Glycopeptide Hormone Functions - Dr. David S. Fay- Top
Dr. David S. Fay, Associate Professor of Molecular Biology and Director of the Molecular and Cellular Life Sciences Program
A Novel Genetic Approach for Elucidating Glycopeptide Hormone Functions
The glyopeptide hormone receptors (GpHRs) are integral membrane proteins that bind to their cognate peptide hormones on the surface of cells. This interaction leads to the transmission of intracellular signals that result in changes in gene expression and physiology. In mammals, there are three members of the GpHR family that bind to either follicle stimulated hormone (FSH), Luteinizing hormone (LH), or thyroid stimulating hormone (TSH). The FSH and LH receptors function in a number of important processes including the regulation of sperm and oocyte production. In fact, over fifty distinct mutations have been isolated from human patients with severe reproductive defects that alter the coding sequences of FSH, LH, or their cognate receptors. To learn more about the functions of these receptors and their intracellular signaling components, we have initiated studies using the nematode model system, C. elegans. C. elegans expresses a single GpHR famly member, FSHR-1, which is equally similar to all three mammalian receptors. Our studies have revealed roles for FSHR-1 in promoting ooctye development, germline stem cell proliferation, and germ cell survival. Our future work is focused on using the power of C. elegans genetic analysis to identify previously unknown components of GpHR signaling in mammals. Such proteins may be useful therapeutic targets in cases of human infertility or may provide diagnostic markers for better understanding conditions that lead to infertility.
A Natural Model for the Study of Chronic and Acute Renal Failure - Dr. Henry J. Harlow- Top
Dr. Henry J. Harlow, Professor of Zoology and Physiology
A Natural Model for the Study of Chronic and Acute Renal Failure
Humans suffer from a variety of renal pathologies that influence blood volume and pressure regulation. For example, diabetes insipidus is a disease affecting the kidney that is associated with long periods of diuresis, water loss, hypotension, and dehydration caused by low levels of the antidiuretic hormone, AVP. The treatment of this disease is complicated by large fluctuations in kidney solute and electrolyte gradients in response to AVP replacement. Of equal concern is a suite of disorders referred to as Acute Renal Failure (ARF) which is associated with a large decrease of prerenal blood flow and intrinsic glomerular alterations that, unchecked, can result in damage to the kidney tubules and a subsequent loss of the cortico-papillary osmotic gradient needed to conserve urinary water and maintain blood volume. Despite many years of study and advances in treatment, there has been no decline in human deaths from ARF with mortality averaging 50%. As a novel model for study, small mammal hibernators enter bouts of torpor with what appear to be low levels of circulating AVP and extremely low systemic blood pressures resulting in almost complete renal failure; conditions that are similar to diabetes insipidus and ARF. Despite these challenges to the kidney, small mammal hibernators are able to rapidly regain blood pressure and normal kidney function repeatedly every 5-15 days in just 2 hours without any resultant damage to the structure or function of the kidneys. The major goal of this project is to understand how kidneys of hibernators are able to rapidly regain function during arousal from torpor while avoiding the damages seen with untreated diabetes insipidus or ARF. We believe hibernating mammals have a unique capacity to quickly sequester urea as well as counterbalancing and counteracting solutes needed to reinstate a “healthy” kidney capable of conserving water and maintaining blood volume during arousal bouts. The control of blood pressure, sensitivity of vascular tissue and timing of renal perfusion are critical to this adaptive response. By understanding how this natural model of extreme renal function is able to operate without ischemic damage to the kidney, we can better treat human renal disorders and associated blood volume regulation.
Development of an Animal Model for Exploring Postpartum Depression - Dr. Gail Leedy- Top
Dr. Gail Leedy, Associate Professor of Social Work
Development of an Animal Model for Exploring Postpartum Depression
Postpartum mood and anxiety disorders exact an enormous cost in terms of maternal and infant health and wellbeing, with potentially grievous consequences including infanticide. There is a continuum of mood disturbances in the period surrounding childbirth ranging from the “blues” to severe depression and even psychosis. The leading hypothesis for the biological cause of postpartum depression is the impact of the abrupt withdrawal of progesterone, at the time of childbirth, on sensitive brain circuits. However, the lack of a valid animal model of postpartum depression has presented a major barrier to understanding the nature of such mechanisms. We are currently beginning our study of changes in brain structures that occur in postpartum animals, using sheep as our primary animal model. Based on preliminary studies, we have determined that providing mild and chronic stressors to ewes during the first three weeks after lambing results in a reduction in maternal motivation. In the next phase of research, we will further refine this model and begin an investigation into the changes which occur in the brain itself in response to stress and the hormonal changes which occur immediately after lambing.
Lineage-specific Processes of Evolution - Dr. David Liberles- Top
Dr. David Liberles, Assistant Professor of Molecular Biology
Lineage-specific Processes of Evolution
Past Project Investigators/Mentors
A Novel Genetic Approach for Elucidating Glycopeptide Hormone Functions
The glyopeptide hormone receptors (GpHRs) are integral membrane proteins that bind to their cognate peptide hormones on the surface of cells. This interaction leads to the transmission of intracellular signals that result in changes in gene expression and physiology. In mammals, there are three members of the GpHR family that bind to either follicle stimulated hormone (FSH), Luteinizing hormone (LH), or thyroid stimulating hormone (TSH). The FSH and LH receptors function in a number of important processes including the regulation of sperm and oocyte production. In fact, over fifty distinct mutations have been isolated from human patients with severe reproductive defects that alter the coding sequences of FSH, LH, or their cognate receptors. To learn more about the functions of these receptors and their intracellular signaling components, we have initiated studies using the nematode model system, C. elegans. C. elegans expresses a single GpHR famly member, FSHR-1, which is equally similar to all three mammalian receptors. Our studies have revealed roles for FSHR-1 in promoting ooctye development, germline stem cell proliferation, and germ cell survival. Our future work is focused on using the power of C. elegans genetic analysis to identify previously unknown components of GpHR signaling in mammals. Such proteins may be useful therapeutic targets in cases of human infertility or may provide diagnostic markers for better understanding conditions that lead to infertility.
A Natural Model for the Study of Chronic and Acute Renal Failure - Dr. Henry J. Harlow- Top
Dr. Henry J. Harlow, Professor of Zoology and Physiology
A Natural Model for the Study of Chronic and Acute Renal Failure
Humans suffer from a variety of renal pathologies that influence blood volume and pressure regulation. For example, diabetes insipidus is a disease affecting the kidney that is associated with long periods of diuresis, water loss, hypotension, and dehydration caused by low levels of the antidiuretic hormone, AVP. The treatment of this disease is complicated by large fluctuations in kidney solute and electrolyte gradients in response to AVP replacement. Of equal concern is a suite of disorders referred to as Acute Renal Failure (ARF) which is associated with a large decrease of prerenal blood flow and intrinsic glomerular alterations that, unchecked, can result in damage to the kidney tubules and a subsequent loss of the cortico-papillary osmotic gradient needed to conserve urinary water and maintain blood volume. Despite many years of study and advances in treatment, there has been no decline in human deaths from ARF with mortality averaging 50%. As a novel model for study, small mammal hibernators enter bouts of torpor with what appear to be low levels of circulating AVP and extremely low systemic blood pressures resulting in almost complete renal failure; conditions that are similar to diabetes insipidus and ARF. Despite these challenges to the kidney, small mammal hibernators are able to rapidly regain blood pressure and normal kidney function repeatedly every 5-15 days in just 2 hours without any resultant damage to the structure or function of the kidneys. The major goal of this project is to understand how kidneys of hibernators are able to rapidly regain function during arousal from torpor while avoiding the damages seen with untreated diabetes insipidus or ARF. We believe hibernating mammals have a unique capacity to quickly sequester urea as well as counterbalancing and counteracting solutes needed to reinstate a “healthy” kidney capable of conserving water and maintaining blood volume during arousal bouts. The control of blood pressure, sensitivity of vascular tissue and timing of renal perfusion are critical to this adaptive response. By understanding how this natural model of extreme renal function is able to operate without ischemic damage to the kidney, we can better treat human renal disorders and associated blood volume regulation.
Development of an Animal Model for Exploring Postpartum Depression - Dr. Gail Leedy- Top
Dr. Gail Leedy, Associate Professor of Social Work
Development of an Animal Model for Exploring Postpartum Depression
Postpartum mood and anxiety disorders exact an enormous cost in terms of maternal and infant health and wellbeing, with potentially grievous consequences including infanticide. There is a continuum of mood disturbances in the period surrounding childbirth ranging from the “blues” to severe depression and even psychosis. The leading hypothesis for the biological cause of postpartum depression is the impact of the abrupt withdrawal of progesterone, at the time of childbirth, on sensitive brain circuits. However, the lack of a valid animal model of postpartum depression has presented a major barrier to understanding the nature of such mechanisms. We are currently beginning our study of changes in brain structures that occur in postpartum animals, using sheep as our primary animal model. Based on preliminary studies, we have determined that providing mild and chronic stressors to ewes during the first three weeks after lambing results in a reduction in maternal motivation. In the next phase of research, we will further refine this model and begin an investigation into the changes which occur in the brain itself in response to stress and the hormonal changes which occur immediately after lambing.
Lineage-specific Processes of Evolution - Dr. David Liberles- Top
Dr. David Liberles, Assistant Professor of Molecular Biology
Lineage-specific Processes of Evolution
Past Project Investigators/Mentors
Development of an Animal Model for Exploring Postpartum Depression
Postpartum mood and anxiety disorders exact an enormous cost in terms of maternal and infant health and wellbeing, with potentially grievous consequences including infanticide. There is a continuum of mood disturbances in the period surrounding childbirth ranging from the “blues” to severe depression and even psychosis. The leading hypothesis for the biological cause of postpartum depression is the impact of the abrupt withdrawal of progesterone, at the time of childbirth, on sensitive brain circuits. However, the lack of a valid animal model of postpartum depression has presented a major barrier to understanding the nature of such mechanisms. We are currently beginning our study of changes in brain structures that occur in postpartum animals, using sheep as our primary animal model. Based on preliminary studies, we have determined that providing mild and chronic stressors to ewes during the first three weeks after lambing results in a reduction in maternal motivation. In the next phase of research, we will further refine this model and begin an investigation into the changes which occur in the brain itself in response to stress and the hormonal changes which occur immediately after lambing.
Lineage-specific Processes of Evolution - Dr. David Liberles- Top
Dr. David Liberles, Assistant Professor of Molecular Biology
Lineage-specific Processes of Evolution
Past Project Investigators/Mentors
Maternal Undernutrition and its Effects on Fetal Heart Gene Expression - Dr. Hyung Chul Han, Dr. Thomas R. Hansen- Top
Dr. Hyung Chul Han Project Investigator, Research Assistant Professor
Post Doctoral Research Associate, Animal Science
hanh@uwyo.edu
Dr. Thomas R. Hansen Mentor/Collaborator
Professor, Animal Science
thansen@uwyo.edu
Summary:
Hypothesis: Maternal undernutrition programs gene expression in fetal heart contributing cardiac dysfunction later in life. AT2 mediates fetal cardiac hypertrophy through type 1 (AT2R1) and type 2 (AT2R2) receptors that are coupled to gene products identified via subtractive screening of fetal LV mRNA.
Nutrient restriction will occur during the first half of gestation. Fetuses will be collected on day 78 to complete the following aims. The primary comparison will be between fetal LV collected from control-fed and nutrient restricted ewes on day 78 of gestation.
1. Determine circulating AT2 and aldosterone levels in fetal blood on day 78 of gestation in nutrient restricted and control-fed ewes.
2. Determine morphological changes, degree of collagen staining, and localization of AT2R1 and AT2R2 in fetal LV using in situ hybridization and immunohistochemistry.
3. Localize mRNAs shown to be differentially expressed in fetal LV using in situ hybridization and where appropriate, associated proteins using immunohistochemistry.
4. Determine if AT2 induces transcription of differentially expressed genes in cultured cardiac myocytes and fibroblasts.
Identification of Signal Pathways Involved in Transmitter-mediated Vasopressin Release - Dr. Francis W. Flynn- Top
Dr. Francis W. Flynn, Mentor/Collaborator
Director, Graduate Neuroscience Program
flynn@uwyo.edu
Summary:
The rational for the proposal is provided by findings that: the paraventricular nucleus of the hypothalamus (PVN) is dense with tachykinin NK3 receptors; injections of NK3 receptor agonists intraventricularly or into the PVN stimulate vasopressin (VP) release; and the majority of VP immunoreactive (IR) neurons express NK3 receptors. The tachykinin peptide, neurokinin B (NKB) shows the highest affinity for the NK3 receptor but the NKB innervation of the PVN and the subcellular distribution of NKB in the PVN is unknown.
Aim 1 will use immunohistochemistry and retrograde tract tracing to test the hypothesis that NKB neurons project to the PVN. Our Preliminary Results show that NKB terminals are present in the PVN but the source of these NKB afferents is unknown. NKB projections to the PVN will be determined by injecting a retrograde tracer into the PVN and combining that with NKB immunohistochemistry. Several nuclei, including the subfornical organ (SFO), arcuate nucleus, and bed nucleus of the stria terminalis (BNST), project to the PVN and contain NKB immunoreactive soma.
Aim 2 will utilize transmission electron microscopy to characterize the subcellular distribution of NKB and test the hypothesis that NKB may be released from dendrites of PVN neurons. The majority of magnocellular PVN neurons express both VP and NKB. The physiological action(s) of NKB that is expressed by PVN neurons is unknown. Studies show that VP is released from the dendrites of PVN neurons and the co-localization of NKB and VP raises the possibility of a dendritic release of NKB. This would be consistent with the proposal that there is an intranuclear release of NKB from PVN neurons, which stimulates proximal NK3 receptors. We will use electron microscopy to determine if the subcellular organization of NKB immunoreactivity is consistent with a somatic or dendritic release of NKB.
Placentomal Vascular Adaptations to Early maternal Nutrient Restriction in the Ewe - Dr. Meijun Zhu, Dr. Stephen P. Ford- Top
Principal Investigator: Dr. Meijun Zhu, Research Associate, Department of Animal Sciences
Mentor: Dr. Stephen P. Ford, Professor & Rochelle Chair Reproductive Biology, Department of Animal Sciences
Placentomal vascular adaptations to early maternal nutrient restriction in the ewe.
Initial studies demonstrated that the environment under which a ewe was selected prior to study influenced her sensitivity to a bout of maternal nutrient restriction. Ewes were selected from two flocks originally derived from the same population ~30 years ago, and 1) subjected to a harsh nomadic existence with limited nutritional inputs near Baggs, WY (Baggs ewes), and 2) maintained by the University of Wyoming under optimal conditions and receiving more than adequate nutritional input (UW ewes). When subjected to a nutrient restriction (50% of NRC recommendations) from day 28 to day 78 of gestation, nutrient restricted (NR) Baggs ewe lost less body weight and body condition than NR UW ewes. Further, while NR and control fed (CF; 100% of NRC recommendations) Baggs ewes exhibited similar fetal weights and crown rump lengths on day 78, fetuses of NR UW ewes were ~30% lighter and smaller than those of CF UW ewes and exhibited asymmetric organ development . The ability of NR Baggs ewes to maintain normal fetal growth rate was found to be associated with their ability to convert Type A placentomes to more efficient Types B, C, and D in response to early gestational nutrient restriction, NR UW ewes did not. Placentomes are the individual functional units of the ruminant placenta where nutrients from the maternal blood stream are transported to the conceptus, and it had been thought that placentomal conversion only occurred in late gestation as fetal nutrient demands marked increased. The fact that B, C, and D placentomes were more efficient than A placentomes in delivering nutrients to the fetus was confirmed by the fact that NR and CF Baggs fetuses had normal blood levels of glucose and essential amino acids (major fetal substrates for energy and growth), while NR UW fetuses had markedly lower blood levels of glucose and essential amino acids than CF UW fetuses. We then set out to evaluate anatomical and physiological differences between placentomal types. We found that as placentomes progressed from Type A to Types B, C, and D, both the cotyledonary (COT, placental portion) and the caruncular (CAR, maternal portion) components progressively increased in size, blood vessels/unit COT and CAR tissue area (image analysis) and blood flow per g of COT and CAR tissue (fluorescent microsphere infusion). We further determined that the MAPK/ERK1/2 and PIP3-K/Akt growth signaling pathways were important in modulating placentomal vascularity (Western analysis and Immunohistochemistry). We next asked whether alterations in placentomal phenotype were associated with gene expression differences as placentomes progressed from Type A to D. RNA isolated from 3 NR UW Type A placentomes (UWA), and 3 NR Baggs Type A, B, C and D PLACs (BA, BB, BC and BD) were used to probe 15 Affymetrix Bovine Genome Arrays. Preliminary analysis of the microarray data identified 50 differentially expressed genes (≥2X; p<0.05) between UWA and BA, 99 between BA and BB, 7 between BB and BC, and 13 between BC and BD. The results suggest that differences in gene expression between UWA and BA PLACs may be responsible for the transformation of Type A to B PLACs, and remain critical for B to D transformations as well. We are now beginning the process of confirming differential gene expression in ovine placentomal tissues using Real time PCR techniques. By understanding the pattern of gene expression associated with placentomal conversion, a greater understanding of the factors mediating increased placental efficiency can be achieved.
Developing Capacity for Community-Focused Health Research - Dr. Sharon A. Cumbie, Dr. Clarann L. Weinert- Top
Dr. Sharon A. Cumbie, Project Investigator
Assistant Professor, College of Nursing
sacumbie@uwyo.edu
Dr. Clarann L. Weinert, Mentor/Collaborator
Professor, College of Nursing
Montana State University
cweinert@montana.edu
Summary
Geographical, environmental, sociological, and cultural elements inherent to rural populations of Wyoming often prohibit the people of the state from benefiting from many current national health initiatives. Due to restraints related to inadequate infrastructures for the delivery of services, smaller communities often lack adequate access to health care and health promotional services. As a step in ameliorating these problems, the intention of the proposed initiative is to develop campus-community partnerships for health with underserved communities of Wyoming through the development of a multidisciplinary research and community health intervention infrastructure. The implementation of a multidisciplinary community-centered model for statewide health promotion has the potential to make a national dream of health quality, set forth in Healthy People 2010, a reality to the citizens of Wyoming.
The long-range objective of the project is to establish and maintain long-term campus-community partnerships to advance interdisciplinary research related to rural community health that will contribute to the quality of life among the citizens of Wyoming. In order to meet these needs, we must recast the entire system of clinical research if such efforts are to become meaningful to rural and frontier populations. Clinical research needs to develop new partnerships among organized community populations, service organizations, community-based care providers, community colleges and academic researchers. The objective of this proposed health initiative is to re-engineer the clinical research enterprise by developing a systematic infrastructure that will better support Wyoming health researchers to participate in collaborative efforts and contribute to the evolving field of health related scientific discovery and health quality improvement.
Director, Graduate Neuroscience Program
flynn@uwyo.edu
Summary:
The rational for the proposal is provided by findings that: the paraventricular nucleus of the hypothalamus (PVN) is dense with tachykinin NK3 receptors; injections of NK3 receptor agonists intraventricularly or into the PVN stimulate vasopressin (VP) release; and the majority of VP immunoreactive (IR) neurons express NK3 receptors. The tachykinin peptide, neurokinin B (NKB) shows the highest affinity for the NK3 receptor but the NKB innervation of the PVN and the subcellular distribution of NKB in the PVN is unknown.
Aim 1 will use immunohistochemistry and retrograde tract tracing to test the hypothesis that NKB neurons project to the PVN. Our Preliminary Results show that NKB terminals are present in the PVN but the source of these NKB afferents is unknown. NKB projections to the PVN will be determined by injecting a retrograde tracer into the PVN and combining that with NKB immunohistochemistry. Several nuclei, including the subfornical organ (SFO), arcuate nucleus, and bed nucleus of the stria terminalis (BNST), project to the PVN and contain NKB immunoreactive soma.
Aim 2 will utilize transmission electron microscopy to characterize the subcellular distribution of NKB and test the hypothesis that NKB may be released from dendrites of PVN neurons. The majority of magnocellular PVN neurons express both VP and NKB. The physiological action(s) of NKB that is expressed by PVN neurons is unknown. Studies show that VP is released from the dendrites of PVN neurons and the co-localization of NKB and VP raises the possibility of a dendritic release of NKB. This would be consistent with the proposal that there is an intranuclear release of NKB from PVN neurons, which stimulates proximal NK3 receptors. We will use electron microscopy to determine if the subcellular organization of NKB immunoreactivity is consistent with a somatic or dendritic release of NKB.
Placentomal Vascular Adaptations to Early maternal Nutrient Restriction in the Ewe - Dr. Meijun Zhu, Dr. Stephen P. Ford- Top
Principal Investigator: Dr. Meijun Zhu, Research Associate, Department of Animal Sciences
Mentor: Dr. Stephen P. Ford, Professor & Rochelle Chair Reproductive Biology, Department of Animal Sciences
Placentomal vascular adaptations to early maternal nutrient restriction in the ewe.
Initial studies demonstrated that the environment under which a ewe was selected prior to study influenced her sensitivity to a bout of maternal nutrient restriction. Ewes were selected from two flocks originally derived from the same population ~30 years ago, and 1) subjected to a harsh nomadic existence with limited nutritional inputs near Baggs, WY (Baggs ewes), and 2) maintained by the University of Wyoming under optimal conditions and receiving more than adequate nutritional input (UW ewes). When subjected to a nutrient restriction (50% of NRC recommendations) from day 28 to day 78 of gestation, nutrient restricted (NR) Baggs ewe lost less body weight and body condition than NR UW ewes. Further, while NR and control fed (CF; 100% of NRC recommendations) Baggs ewes exhibited similar fetal weights and crown rump lengths on day 78, fetuses of NR UW ewes were ~30% lighter and smaller than those of CF UW ewes and exhibited asymmetric organ development . The ability of NR Baggs ewes to maintain normal fetal growth rate was found to be associated with their ability to convert Type A placentomes to more efficient Types B, C, and D in response to early gestational nutrient restriction, NR UW ewes did not. Placentomes are the individual functional units of the ruminant placenta where nutrients from the maternal blood stream are transported to the conceptus, and it had been thought that placentomal conversion only occurred in late gestation as fetal nutrient demands marked increased. The fact that B, C, and D placentomes were more efficient than A placentomes in delivering nutrients to the fetus was confirmed by the fact that NR and CF Baggs fetuses had normal blood levels of glucose and essential amino acids (major fetal substrates for energy and growth), while NR UW fetuses had markedly lower blood levels of glucose and essential amino acids than CF UW fetuses. We then set out to evaluate anatomical and physiological differences between placentomal types. We found that as placentomes progressed from Type A to Types B, C, and D, both the cotyledonary (COT, placental portion) and the caruncular (CAR, maternal portion) components progressively increased in size, blood vessels/unit COT and CAR tissue area (image analysis) and blood flow per g of COT and CAR tissue (fluorescent microsphere infusion). We further determined that the MAPK/ERK1/2 and PIP3-K/Akt growth signaling pathways were important in modulating placentomal vascularity (Western analysis and Immunohistochemistry). We next asked whether alterations in placentomal phenotype were associated with gene expression differences as placentomes progressed from Type A to D. RNA isolated from 3 NR UW Type A placentomes (UWA), and 3 NR Baggs Type A, B, C and D PLACs (BA, BB, BC and BD) were used to probe 15 Affymetrix Bovine Genome Arrays. Preliminary analysis of the microarray data identified 50 differentially expressed genes (≥2X; p<0.05) between UWA and BA, 99 between BA and BB, 7 between BB and BC, and 13 between BC and BD. The results suggest that differences in gene expression between UWA and BA PLACs may be responsible for the transformation of Type A to B PLACs, and remain critical for B to D transformations as well. We are now beginning the process of confirming differential gene expression in ovine placentomal tissues using Real time PCR techniques. By understanding the pattern of gene expression associated with placentomal conversion, a greater understanding of the factors mediating increased placental efficiency can be achieved.
Developing Capacity for Community-Focused Health Research - Dr. Sharon A. Cumbie, Dr. Clarann L. Weinert- Top
Dr. Sharon A. Cumbie, Project Investigator
Assistant Professor, College of Nursing
sacumbie@uwyo.edu
Dr. Clarann L. Weinert, Mentor/Collaborator
Professor, College of Nursing
Montana State University
cweinert@montana.edu
Summary
Geographical, environmental, sociological, and cultural elements inherent to rural populations of Wyoming often prohibit the people of the state from benefiting from many current national health initiatives. Due to restraints related to inadequate infrastructures for the delivery of services, smaller communities often lack adequate access to health care and health promotional services. As a step in ameliorating these problems, the intention of the proposed initiative is to develop campus-community partnerships for health with underserved communities of Wyoming through the development of a multidisciplinary research and community health intervention infrastructure. The implementation of a multidisciplinary community-centered model for statewide health promotion has the potential to make a national dream of health quality, set forth in Healthy People 2010, a reality to the citizens of Wyoming.
The long-range objective of the project is to establish and maintain long-term campus-community partnerships to advance interdisciplinary research related to rural community health that will contribute to the quality of life among the citizens of Wyoming. In order to meet these needs, we must recast the entire system of clinical research if such efforts are to become meaningful to rural and frontier populations. Clinical research needs to develop new partnerships among organized community populations, service organizations, community-based care providers, community colleges and academic researchers. The objective of this proposed health initiative is to re-engineer the clinical research enterprise by developing a systematic infrastructure that will better support Wyoming health researchers to participate in collaborative efforts and contribute to the evolving field of health related scientific discovery and health quality improvement.
Assistant Professor, College of Nursing
sacumbie@uwyo.edu
Dr. Clarann L. Weinert, Mentor/Collaborator
Professor, College of Nursing
Montana State University
cweinert@montana.edu
Summary
Geographical, environmental, sociological, and cultural elements inherent to rural populations of Wyoming often prohibit the people of the state from benefiting from many current national health initiatives. Due to restraints related to inadequate infrastructures for the delivery of services, smaller communities often lack adequate access to health care and health promotional services. As a step in ameliorating these problems, the intention of the proposed initiative is to develop campus-community partnerships for health with underserved communities of Wyoming through the development of a multidisciplinary research and community health intervention infrastructure. The implementation of a multidisciplinary community-centered model for statewide health promotion has the potential to make a national dream of health quality, set forth in Healthy People 2010, a reality to the citizens of Wyoming.
The long-range objective of the project is to establish and maintain long-term campus-community partnerships to advance interdisciplinary research related to rural community health that will contribute to the quality of life among the citizens of Wyoming. In order to meet these needs, we must recast the entire system of clinical research if such efforts are to become meaningful to rural and frontier populations. Clinical research needs to develop new partnerships among organized community populations, service organizations, community-based care providers, community colleges and academic researchers. The objective of this proposed health initiative is to re-engineer the clinical research enterprise by developing a systematic infrastructure that will better support Wyoming health researchers to participate in collaborative efforts and contribute to the evolving field of health related scientific discovery and health quality improvement.
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University of Wyoming
1000 E. University Ave.
Laramie, WY 82071
(307) 766-6751
e-mail: hsawyer@uwyo.edu
