China Scholarship Council-Georgetown University Fellowship Program
List of Calls for Applications for 2008-09 Fellowships
1. Department of Biochemistry and Molecular and Cell Biology
Contact Information
Anita Sidhu, Ph.D.,Professor and Head of Laboratory of Molecular Neurochemistry,Department of Biochemistry and Molecular and Cell Biology,
Description of Research
Our laboratory has recently described a novel pathway whereby α-synuclein, a protein linked to Parkinson’s disease, can cause the hyperphosphorylation of Tau [p-Tau], a protein linked to Alzheimer’s disease, thereby implicating p-Tau in the genesis of PD and α-Syn in the genesis of AD. This pathway has been confirmed in MPTP animal models of PD as well as in human post-mortem tissues. Published studies can be found in PubMed.
We would now like to understand the mechanism by which environmental toxins induce neurodegenerative changes leading to synucleopathies and tauopathies in cell and animal models; to develop biomarkers for early identification of these diseases and to develop novel treatment strategies for the prevention of neurodegeneration. Wild type and transgenic mice overexpressing α-synuclein will be treated with rotenone or MPTP, and changes in α-synuclein, p-Tau [phosphorylated at different sites identified by Western blots and proteomics], and associated kinases and phosphatases will be identified. Immunohistochemistry will be used to confirm neurodegeneration. MRI and MRS will be used to measure changes in vivo, enabling us to longitudinally follow disease progression within the same animal, particularly during the early stages of neurodegeneration, for developing possible biomarkers in humans. We will explore several neuroprotective strategies to prevent or reduce the severity of neurodegenerative changes. We will test a novel groups inhibitor in preventing activation of Tau-specific kinases. We will also test the neuroprotective effect of parkin, through lentiviral delivery in specific brain regions, to examine accelerated clearance of aggregates of α-synuclein and p-Tau via proteosomes.
Specific Requirements for Fellows
A strong background and interest in neurodegenerative diseases or neuroscience, as evidenced by publications is mandatory. Prior experience in two or more of the following techniques is also desirable: signal transduction, study of kinases, immunohistochemistry, whole animal studies and stereotaxic surgery, molecular and neurochemical techniques, MRI or MRS experience.
Research Project of the desired postdoctoral fellow
Will depend on the past research experience of the fellow, but will involve one or more of the above listed projects ongoing in the laboratory.
2. Department of Neuroscience
Contact Information
Michael T. Ullman, PhD., Associate Professor, Director, Brain and Language Laboratory, co-Director, Center for the Brain Basis of Cognition, Department of Neuroscience,
Description of Research
The fellow would perform research investigating the neurocognitive (biological, computational and psychological) bases of language and its relation to memory -- specifically, its relation to two well-studied brain memory systems, declarative and procedural memory. The research could be either on first (native) language and/or second (later-learned) language. We are interested in the effects of different types of L2 training on the neurocognition of L2 learning and longer-term retention. We are also very interested in individual and group differences in the neurocognition of language, including those related to sex (male vs. female), handedness, and genetic variability. We examine language both in normal children and adults, and in disordered populations (autism, dyslexia, specific language impairment, ADHD, Tourette's syndrome, Alzheimer's disease, Parkinson' disease, Huntington's disease, aphasia), both with behavioral studies and with neuroimaging (fMRI and ERPs). For more details and relevant papers see brainlang.georgetown.edu
Specific Requirements for Fellows:
cognitive neuroscience; neuroscience; cognitive psychology ADDITIONALLY: training/experience in at least one of the following is very desirable. Statistics, computer science,linguistics. Finally, specific training/experience in one or more of the following would be advantageous: fMRI, ERPs.
3. Department of Biochemistry and Molecular & Cellular Biology
Contact Information
Cathy H. Wu, Ph.D., Professor and Director of Protein Information Resource, Department of Biochemistry and Molecular & Cellular Biology,
Description of Research
Dr. Cathy Wu, Director of Protein Information Resource (PIR), has conducted bioinformatics research since 1990 and has published about 130 peer-reviewed papers and three books. PIR provides bioinformatics resource to support proteomics and systems biology research. It is a member of the UniProt Consortium to provide the central resource on protein sequence and function, and is a key member of the NCI caBIG (cancer Biomedical Informatics Grid) program and the NIAID biodefense proteomics program. PIR also leads the Protein Ontology consortium to develop an ontology of protein evolution and protein modified forms. The PIR web site and the UniProt web site at PIR are accessible by researchers worldwide with over 4 million hits per month from over 100,000 unique sites. Below is a summary of the PIR integrated protein bioinformatics system.
Systems integration is becoming the driving force for 21st century biology. Researchers are systematically tackling gene functions and complex regulatory processes by studying organisms at different levels of organization, from genomes, transcriptomes, proteomes, peptidomes, to metabolomes and interactomes. These studies provide a global view of gene function and temporal and spatial regulation of genes in different disease states. To fully realize the value of such high-throughput datarequires advanced bioinformatics for integration, mining, comparative analysis, and functional interpretation. We are developing a protein-centric bioinformatics framework for functional and pathway analysis in the systems biology context. The integration of bioinformatics tools with a large number of biomedical databases in such a framework will support associative analysis of expressed genes, proteins, peptides, metabolites and pathways; thereby revealing hidden interrelationships among the various components of the biological systems. The integrative approach will allow researchers to ask complex biological questions, gain better understanding of disease processes, and facilitate biomarker and drug target discovery.
The post-doc will be involved in research project that is synergistic and complementary to other PIR projects. The major research areasconducted by Dr. Wu’s research team at PIR include protein family classification and structure-function analysis for protein annotation, biological data integration, proteomicsand systems biology informatics, and biomedical text mining and ontology.
Protein Information Resource (PIR):
Cathy Wu:
Specific Requirements for Fellows
The fellow should have basic knowledge in both biomedical sciences and bioinformatics.
4. Department of Physiology and Biophysics
Contact Information
Jian-young Wu, Ph.D., Professor, Department: Physiology and biophysics,
Description of Research
Dr. Wu studies the dynamic process of neuronal activity in the brain, including how a large scale neuronal activity such as sensory, motor or thinking is developed from the activity of few neurons. In particular we examine spatiotemporal patterns of neuronal activities in the mammalian neocortex. His major tool for visualizing the neuronal activities in the cortex is voltage-sensitive dye imaging. Many cortical activities are organized as propagating waves. An ultimate hypothesis is that propagating wave is a basic form of organization for population neuronal activities in the cortex. The waves may be utilized as mechanisms for developing a correlated activity over large spatial range and sustaining an activity after long temporal delays. Dr. Wu's projects are focused how the wave initiate, propagate and organized into different patterns (e.g., spirals).
Dr. Wu's research is also directly related to the understanding of brain disorders such as epilepsy and Parkinson’s disease. These pathological activities share some common neuronal process as the normal brain activity initiation and propagation.
As a world renowned expert of the voltage-sensitive dye imaging community, Dr. Wu also develops specialized cameras with extremely high dynamic range for detecting small optical signals at very fast frame rates. Voltage-sensitive dye signals are small and imaging propagating waves is technically difficult. A device that Dr. Wu designed, photodiode array, has been used by more than 50 laboratories in the US, Europe and Japan. Dr. Wu's technical development has been contributing to communities in imaging brain and other fields such as imaging cardiac waves. At Georgetown his laboratory (Georgetown Laboratory of Optical Imaging, GLOI) has participated as a core facility in a number of program project grants and is providing service for collecting preliminary imaging data and helping other faculty members to submit grants.
In the past ten years since Dr. Wu joined the Georgetown faculty, his research has been continuously supported by grants from NIH, epilepsy foundation, Department of Defense and the Whitehall foundation. Dr. Wu's collaborations with laboratories in China are also supported by The Chinese National Science Foundation and the KC Wang Foundation Fellowship.
The desired post-doc fellow will participate in one of the ongoing projectsin the Wu lab on imaging sensory evoked neuronal activity in rodent cortex. In this project the post-doc will be trained in voltage-sensitive dye imaging, a highly innovative technique. We expect the project can produce one original publication in a duration of one year. The project is fully supported by an active NIH grant studying cortical dynamics. The Wu lab would considercontinuing support for the post-doc fellow when the fellowship is ended if necessary and permitted by CSC.
A full PubMed listed publication can be found at the website:
Specific Requirements for Fellows
A Ph.D from a neurophysiology lab. Experience indicated by publications. General knowledge of neocortex, skills of small animal surgery, neurophysiology recordings.
5. Department of Medicine
Contact Information
Chenglong Liu, PhD, Assistant Professor of MedicineMary A. Young, MD Assistant Professor of Medicine, Department of Medicine, Division of Infectious Diseases, , youngma@georgetown,edu
Description of Research
Our research focuses on almost all aspects of HIV/AIDS related topics under the Women’s Interagency HIV Study (WIHS), the largest HIV/AIDS cohort study among women in the United States which has been ongoing since 1994. WIHS consists of six sites - WashingtonDC, Los Angeles, San Francisco, Chicago, Bronx and Brooklyn, NY and the data coordination center located at JohnsHopkinsUniversity in Baltimore. So far, more than 330 peer-reviewed papers have been published in the leading HIV/AIDS journals, with topics ranging from epidemiology, behavior, immunology, virology, genetics, health service, sexually transmitted diseases, opportunistic infection, cancers, cardiovascular diseases, coinfection with human papillomavirus and hepatitis C etc. Across site and interdisciplinary collaboration has been a culture for WIHS, and the data and specimens collected are open to outside investigators.
As an integral part of WIHS, Georgetown has recruited more than 400 women with or at risk of HIV infection under the leadership of Dr. Mary Young. The women followed are mainly minority and of low socioeconomic status from WashingtonDC, Maryland and Virginia. The cohort represents the HIV/AIDS epidemic among women in the Washington Metropolitan Area, one of the most hard hit areas in the US. Last year, a research team was formed at Georgetown WIHS consisting of two epidemiologists, a family medicine physician and two infectious diseases physicians. Every week, a research meeting is held and research concept sheets, manuscripts and important updates in the HIV/AIIDS field are discussed. Our current research topics cover behavioral, clinical, and immunologic areas.
Given the rich experience we have obtained from WIHS in both cohort operation and longitudinal data analysis, it would be very helpful to translate our HIV/AIDS research experience to developing countries, like China, which are facing an increasing challenge from HIV/AIDS. To our knowledge, no HIV/AIDS cohort exists at this moment in China. In addition, Dr. Young has many years experience in treating HIV patients and is involved in training interns, residents, and fellows. She has also been involved in workshops for Peace Corp, the US Department of State, and has hosted visiting groups including a yearly seminar with public health officials from Russia. Furthermore, Dr. Chenglong Liu has worked for three years in HIV/AIDS prevention in China before he came to pursue his Ph.D. degree at UCLA. Given his experience and personal connections in China, any future collaboration would be much more feasible and productive.
We would like the post-doc to work with WIHS data on research projects especially applicable to resource limited regions. For example, in WIHS we have demonstrated that total lymphocyte count and hemoglobin level can effectively predict HIV progression to AIDS and death after initiation of highly active antiretroviral therapy [1]. In addition, serum albumin was also demonstrated as a powerful predictor for survival among HIV-infected women [2]. Comparing to the convention measures of CD4+ cell count and HIV RNA level, these biomarkers are much cheaper and can be affordable in the developing countries if further studies show their cost-effectiveness. However, as we have collected a huge HIV/AIDS dataset with thousands of variables, research interest for the post-doc are open for discussion.
Website:
Specific Requirements for Fellows
We require the post-doc to have strong background in epidemiology and biostatistical analytical skills. Some knowledge in medicine and experience in HIV/AIDS a plus. Good communication skills are needed.
References:
1.Anastos K, Shi Q, French AL, Levine A, Greenblatt RM, Williams C, DeHovitz J, Delapenha R, Hoover DR: Total lymphocyte count, hemoglobin, and delayed-type hypersensitivity as predictors of death and AIDS illness in HIV-1-infected women receiving highly active antiretroviral therapy.J Acquir Immune Defic Syndr 2004, 35:383-392.
2.Feldman JG, Gange SJ, Bacchetti P, Cohen M, Young M, Squires KE, Williams C, Goldwasser P, Anastos K: Serum albumin is a powerful predictor of survival among HIV-1-infected women.J Acquir Immune Defic Syndr 2003, 33:66-73.
6. Department of Oncology
Contact Information
Saijun Fan, Aassociate Professor, Department of Oncology,
Description of Research
Breast cancer is one of the most common malignancies affecting women worldwide. In USA and China, breast cancer is the second most common malignant condition among women. Genetic predisposition for familial early onset of breast cancer accounts for approximately 5-10% of all breast cancers. Mutations in two autosomal dominant genes, BRCA1 and BRCA2 have been linked to familial breast cancer.
BRCA1 encodes an 1863 amino acid nuclear protein. Evidence implicates a wide role for BRCA1 in the control of gene expression at the level of transcription, cell cycle progression, DNA damage and repair and others. BRCA1 may function as a ‘caretaker’in preserving the integrity of the genome. Loss of this caretaker function may explain why BRCA1 mutations predispose to the developmentof cancer, but it does not by itself explain the predilectionto specific tumor types, particularly breast cancer and otherhormone-dependent tumors. During the past few years, we have accumulated a large amount of research data to establish new biological functions and published 40 articles related to BRCA1 activities in breast cancer and other types of cancers.
Invasion and metastasis are the most insidious and life-threatening aspects of breast cancer. Once the breast cancer becomes invasive, it can disseminate readily through whatever means or conduits are available to it, via the lymphatics and/or vascular channels. Invasion and metastases of breast cancer kill hosts through two processes: local invasion and distant organ injury. Our understanding of the processes of invasion and metastases has improved, but the mechanism contributing to breast cancer invasion and metastasis still lags. Therefore, metastasis has been as an important therapeutic targetin controlling breast cancer. More recently, we started to study the role of BRCA1 and BRCA2 in invasion and metastasis of breast cancer based upon the indications from our previous studies with microarray assays. These novel studies will further explore molecular mechanisms underlying the metastatic cascade for invasion and metastasis of breast cancer, and create new directions for breast cancer marker development and application.
The host professor will: (1) Investigate the regulatory role of the tumor suppressor gene BRCA1 and BRCA2 in breast cancer development, progression and treatment; (2) Study the cytoprotective role of the hepatocyte growth factor/scatter factor in cancer chemosensitivity and radiosensitivity; (3) Isolate and clone new breast cancer-associated genes.
The post-doc fellow is expected to study the role of tumor suppressor gene BRCA1 and BRCA2 in invasion and metastasis of breast cancer by using in vitro and in vivo assays.
Link to department or host professor website and/or related publications:
(1)
(2)
Specific Requirements for Fellows
Background with cancer biology and biochemistry.Specific knowledge and experiencerequired to conduct the research: General biology and biochemistry.
7. Department of Pediatrics
Contact Information
Pedor Jose, Ph.D., Professor and Chief, Department of Pediatrics
Description of research
We have recently reported that activation of D5 dopamine receptor (D5R) decreases Angiotensin II type I receptor (AT1R) protein expression in human and rat renal proximal tubule cells (Hypertension, 42: 787–792; Hypertension, 42: 438; Hypertension, 45: 804-810). In human kidney (HEK 293) cells heterologously overexpressing both human D5R and human AT1R, fenoldopam, the D5R agonist, decreases hAT1R protein level by increasing hAT1R degradation. The effect of fenoldopam on hAT1R expression was noted as early as 20 minutes, too rapid to be accounted for by an alteration in transcription and/or translation. This D5R-mediated AT1R degradation is directed mainly at the glycosylated but not the non-glycosylated hAT1R, which occurs in proteasomes, via the ubiquitin-proteasome system, and is different from AT1R spontaneous or agonist-induced degradation, which occurs in lysosomes. D5R and AT1R form heterodimers in the transfected HEK 293 cells. Fenoldopam stimulation dissociates D5R from AT1R and initiates AT1R ubiquitylation. The successful candidate(s) will study the mechanisms involved in the D5R-mediated AT1R degradation in proteasomes. Specifically, the candidate will determine the ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2) and ubiquitin ligase (E3) responsible for the D5R-mediated AT1R degradation. The candidate will also determine the signaling pathways involved in the glycosylation, ubiquitination, and intracellular trafficking of AT1R following D5R activation. These studies open a novel pathway in which G protein-coupled receptors (GPCRs) interact. Many of the drugs used today are directed against GPCRs, especially in the treatment of cardiovascular diseases. The candidate will learn not only basic cell physiology but also translational physiology using state-of-the-art imaging techniques such as fluorescence resonance energy transfer, fluorescence lifetime imaging, total internal reflection fluorescence, and bimolecular fluorescence microscopy. Most importantly, the candidate will learn how to construct novel and significant hypotheses, design the experiments, conduct the experiments careful, collect data, interpret the data, and publish the data. The applicant will also learn the importance of scientific integrity and write grant applications in order to become an independent investigator.