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Each Sandler Research Fellow is awarded $15,000 in research funding to complete either a basic science or translational research project. These fellowships are meant to provide postdoctoral fellows with seed money to initiate a novel project that can be continued when they transition to their independent research positions.
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Science at the Cutting Edge
03.03.2008
Regulation and significance of Arp2 phosphorylation
in motile cells (Lawrence LeClaire)
UCSF is home to over 3% of the biomedical postdoctoral fellows in the United States. It is imperative that we provide an environment where postdoctoral fellows can have the opportunity not only to design and complete ground-breaking research but also to develop the professional skills to be successful independent investigators.
The Sandler Postdoctoral Research Fellowships, funded by the Sandler Family Foundation, are designed to encourage creative and independent research driven by postdoctoral scholars. The fellowships support UCSF postdoctoral fellows who wish to explore biomedical research directions that are not directly linked to the research interests of their postdoctoral mentor and require the engagement of an additional collaborator or co-mentor.
In keeping with the mission and spirit of UCSF, these fellowships foster collaborative relationships between research groups at UCSF and support innovative, cutting-edge science.
Charles Harris
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Molecular dissection of glucocorticoid action in metabolic syndrome. My work aims to understand how glucocorticoids cause obesity, diabetes, osteoporosis and muscle loss. The research should also determine if glucocorticoid signaling is involved in the obesity and diabetes that is associated with a high-fat Western diet. |
| My efforts are focused on elucidating the molecular mechanism of quinoline drug resistance in Plasmodium falciparum, the parasite which causes most forms of malaria in humans. A detailed understanding of this resistance would facilitate significant inroads in public health. |
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Musculoskeletal disorders affecting the bones are a growing health problem. My ongoing research has shown that young mice have an enormous bone-forming capacity. I plan to extend these findings by examining whether the healing response to local bone injury is affected by hormone signals. The results promise to reveal new mechanisms of bone repair and potentially improve treatments for bone injuries. |
| Regulation and significance of Arp2 phosphorylation in motile cells. Migrating cells depend on the actin-related protein 2/3 complex (Arp2/3complex) as a regulator of cytoskeletal assembly. My project examines how the Arp2/3 complex is controlled by phosphorylation in response to migratory cues and how Arp2/3 complex phosphorylation regulates cell migration and membrane protrusion. |
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Mitochondrial morphology and dynamics: a computational imaging approach. Mitochondrial shapes range from small individual organelles to giant reticular networks of tubules. My goals are to understand how the shape of these complex structures is determined, how their remodeling is regulated in response to changes in environmental conditions and how mitochondrial morphology affects cell functions. |
| Influence of peripheral temperature detection on core body temperature regulation. Temperature detection and regulation is of vital importance to any homeothermic organism. Our previous work has shown that the TRP ion channels TRPM8 and TRPV1 are important for the sensation of environmental temperatures. Mice deficient for TRPM8 and TRPV1 are severely impaired in their ability to detect cold and hot temperatures respectively. These mouse lines will be used to analyze the role of peripheral temperature detection on core body temperature regulation. |
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Identifying targets and genetic interactions of Mediator subunits in a metazoan. Some subunits of the so-called Mediator complex, which affects gene transcription, are implicated in diseases. My current work aims to investigate the Mediator genes mdt-28 and cdk-8 in the model organism C. elegans. Specifically, I shall elucidate genetic interactions and transcriptional targets of these specific Mediator subunits, allowing us to learn about their biological roles in health and disease. |
| Understanding the role of microRNAs in T Cell tolerance and auto-immunity. Inappropriate T cell responses that are directed towards the body’s own tissues are a root cause of many human diseases. In collaboration with Dr. Michael McManus, we aim to identify microRNAs that specifically influence self-reactive T lymphocytes. These studies will provide valuable insights for the pathogenesis of autoimmunity and could facilitate discovery of novel therapeutics meant to curb excessive, T cell-driven inflammation. |
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Investigating a role for the proteosome in mRNA export. A large-scale genetic interaction study has identified an exciting connection between Sem1/Dss1, a component of the proteasome, and the Sac3-Thp1 mRNA transcription and export complex. I plan to further investigate the role of Sem1/Dss1 and the proteasome in mRNA export. Sem1/Dss1 is conserved from yeast to humans and also binds to BRCA2 (a breast cancer susceptibility protein) in humans, suggesting that an understanding of this novel function will be important for understanding its roles in disease progression. |
| Role of estrogen signaling in the arcuate nucleus of hypothalamus in regulation of feeding behavior. Gonadal hormone estrogen exerts a powerful influence on feeding behaviors and metabolism. My project is designed to examine the expression of estrogen receptor alpha (ERα) in the arcuate nucleus of hypothalamus and the role of ERα signaling in regulating arcuate neuropeptide expression and food intake. These studies will help to unravel the mechanism by which a sex hormone known to regulate reproductive behavior affects energy homeostasis. |
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Investigating the role of Notch signaling in bronchiolitis obliterans/organizing pneumonia (BOOP). I am investigating the role of Notch pathway activation in the fibrotic lung disease bronchiolitis obliterans / organizing pneumonia (BOOP for short). Using a mouse model, I have determined that activated Notch4 overexpression in lung epithelial cells results in symptoms similar to human BOOP. This research may lead to a better understanding of this lung disorder and potential novel therapeutic avenues. |
| Functional analysis of miR-21 involvement in HER2/neu-mediated cancer cell invasion. Using a miRNA array, I have identified a putative oncogenic miRNA, miR-21, whose expression is correlated with HER2/neu upregulation. Importantly, inhibition of miR-21 activity significantly compromised the HER2/neu mediated cancer cell invasion, suggesting that miR-21 might be an important player for HER2/neu induced tumor metastasis. This study could direct an effective approach for development of anti-metastasis therapeutics via repression of this miRNA. |
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Evaluating GRK2 kinase inhibition as a novel strategy for treating cardiac hypertrophy and failure. G protein-coupled receptor kinase-2 (GRK2) is a GPCR regulatory protein that has generated considerable attention as a therapeutic target for heart disease. However, the specific contribution of GRK2 kinase activity in vivo has not yet been assessed, due to a lack of experimental tools available. I have developed a new "chemical genetics"-based model that will allow for evaluating GRK2 kinase inhibition on cardiac function in vivo. |
| Noise or adaptive tuning? Measuring directional tuning in human motor planning areas and their contribution to movement variability using fMRI. This project centers on using fMRI to look for evidence of experience dependent plasticity in brain regions that plan rapid shifts of gaze (e.g. saccades). By adopting ultra-high resolution spatial resolution imaging along with single-trial analysis techniques, we can observe evidence of the directional tuning of the cells that plan eye movements in humans and see how this tuning changes with recent experience. |
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