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All seminars are held at 5:00 p.m. in the Eurosuites Hotel located at 501 Chestnut Ridge Road, Morgantown, West Virginia
September 14, 2004 - Endocrine Disruption
Over the past 50 years, biologists have found that populations of specific wildlife were experiencing declines in their numbers. The wildlife included alligators, fish and birds in the US and in European (“Industrialized”) countries. In many instances the declining populations were found to be due to decreasing reproductive capacities of the mature adults, not due to death of the adults. Some of the sites were associated with blatant pollutant spills. When the pollutants were analyzed and tested for their effects on reproduction, novel effects were discovered in which the pollutants altered hormone-regulated processes, giving rise to the term “Endocrine Disrupting Chemicals (EDCs)” or Hormonally Active Agents (HAAs)”. Epidemiological studies now demonstrate that some of the decreasing wildlife populations are due to the impact of man-made EDCs on hormone-regulated processes associated with reproduction. Many of the EDCs exert deleterious effects by mimicking estrogen or by exerting anti-estrogenic effects; these specific EDCs are termed “xenoestrogens”.
In 1993 Theo Colborn published a book “Our Stolen Future” - she indicated that since WWII large amounts of industrial-derived chemicals that can modulate the hormone system (EDCs) have been released into the environment. She speculated that exposure to these chemicals could result in permanent & irreversible damage to wildlife & to humans. The implication was that human exposure to EDCs could be a major factor in diseases such as: breast cancer, prostrate cancer, testicular cancer, cervical cancer, ovarian cancer, cryptorchidism (testicle[s] not descending properly), decreased sperm counts, hypospadias (displaced urethral opening), premature breast development, negative impacts on the immune system, etc. This book spurred debate and research, with much EMOTION, and with regulatory, legal, environmental and health implications. While it is clear that EDCs have had, and continue to have, a negative impact on some wildlife populations, controversy still surrounds the potential impact of these chemicals on human health.
A panel discussion will address this topic. Panel participants:
Christy Foran, Dept. Biology, Eberly College of Arts & Sciences
Lisa Holland, Dept. Chemistry, Eberly College of Arts & Sciences
Mike Miller, Dept. Biochemistry & Mol. Pharm., Health Sciences Center
Rosana Schafer, Dept. Microbiology, Immunology & Cell Biology, Health Sciences Center
Click Speaker's name to view their presentation
September 28, 2004 - Nanotechnology, Nanoscience and WVNano - Presented by: Dr. Peter Gannett, Associate Chair, WVU Basic Pharmaceutical Sciences. The WVNano Initiative, formally begun in July of 2004, has evolved as a product of the Faculty Nanotechnology Committee in the context of potential infrastructure support under the National Science Foundation Experimental Program to Stimulate Competitive Research (NSF-EPSCoR) and the National Nanotechnology Initiative (NNI). As the result of a year long study and evaluation of the Committee, West VirginiaUniversity has embarked upon a nanoscale science, engineering, and education (NSE) initiative. Nanotechnology and nanoscience has produced significant advances in biotechnology (nanobiotechnolgy) in a large part due to its unparallelled level of sensitivity. It is capable of detection at the single molecule level and has been applied to DNA, RNA, and enzymes. A brief overview of nanotechnology applications will be presented. Current research in nanoscience at WVU that is being conducted by WVNano Faculty under the theme of Multifunctional Nanostructured Systems will also be described. Finally, opportunities in NSE for HSC Researchers will be described.
October 12, 2004 - Canceled
October 25, 2004 - Canceled
November 9, 2004 - Kevin Gaido, Ph.D., CIIT Centers for Health Research, North Carolina
Gene expression profiling following in utero exposure to phthalate esters reveals new gene targets in the etiology of testicular dysgenesis. Male reproductive tract development is a complex process driven primarily by fetal testicular production of multiple hormones and signaling factors. Disturbance in either the timing or concentration of these factors, either through genetic mutation or by pharmaceutical or environmental interference, can have a dramatic effect on the developing male reproductive tract and can result in cryptorchidism (undescended testes), hypospadias (malformed penis), reduced fertility, and testicular cancer. Cryptorchidism and hypospadias are the two most common birth defects in males and there is growing concern that testicular cancer and male-related fertility problems are on the rise. Testicular dysgenesis syndrome was coined to link abnormal fetal testicular development, as a result of genetic mutation or environmental disturbance, with adverse male reproductive function. Male reproductive tract abnormalities associated with testicular dysgenesis in humans also occur in male rats exposed gestationally to some phthalate esters. We examined global gene expression in the fetal testis of the rat following in utero exposure to a panel of different phthalates, including several phthalates known to similarly disrupt male rat reproductive tract development. The developmentally toxic phthalates were remarkably similar in their effects on gene expression. Gene pathways disrupted include the previously identified cholesterol transport and steroidogenic pathways as well as newly identified genes involved in intracellular lipid and cholesterol homeostasis, transcriptional regulation, and response to oxidative stress. The gene pathways targeted by the developmentally toxic phthalates give new insight into the molecular pathways involved in testicular dysgenesis.
November 23 , 2004 - Holiday
December 14, 2004 - Molecules to Medicines: Drug Discovery and Development at WVU-presented by-Dr. Patrick Callery, Chair - WVU Department of Basic Pharmaceutical Science. Systems biology employs computational approaches for a better understanding of complex biological systems. A desired outcome of systems biology information is the provision of a foundation for understanding disease processes. An example of an ultimate outcome is the discovery of new therapeutic approaches.
When announcing biomedical research advancements, many interviews end with, “…and then a drug will be discovered.” There is increasing awareness that there are wasted opportunities by leaving drug discovery and development to the pharmaceutical industry. The academic community is accepting the formidable challenges associated with discovering and developing new therapeutic agents.
Modern drug discovery emphasizes computationally-derived relationships among functional biological target systems and complementary molecules with affinity for target binding regions. Drug development converts new chemical entities to drugs by lead structure optimization, in vitro screening, pre-clinical pharmacology, formulation and drug delivery technology, Phase 1-3 evaluations, new drug applications, and other pre- and post-marketing considerations.
Topics to be discussed include intellectual property issues and patenting with special focus on adding value to each step of the process of turning an idea into a drug.
The speaker, Patrick Callery, was trained in pharmaceutical chemistry at the University of California, San Francisco and was a faculty member at the University of Maryland where he designed and patented antihypertensive benzimidazole analogues, technetium-based hepatobiliary imaging agents, and azetidine polyamine anticancer agents. He lists more publications than he is old in years in areas including medicinal chemistry, drug metabolism and biomedical mass spectrometry.
December 28, 2004 - Holiday
January 11, 2005 - Canceled
January 25 , 2005 - "Identifying targets and dwsigning molecular inhibitors that block invasion in cancer" - Daniel Flynn, Ph.D., Mary Babb Randolph Cancer Center, West Virginia University
February 8, 2005 - "Systems Biology, Cancer and Chronic Disease in West Virginia, and Data Access - a view from the Cancer registry". Alan Ducatman, MD MS, Professor & Chair, West Virginia University Department of Community Medicine. This talk will cover three topics 1) Systems Biology from an epidemiologic perspective 2) Cancer in West Virginia, are there opportunities here? 3) How do you get population cancer data? The focus on the talk will be on population research opportunity areas. (This lecture was created by Pat Colsher, Ph.D. director, WV Cancer Registry)
February 22,, 2005 - "Quantitative Protein Profiling and Integration with DNA Sequence and mRNA Expression Profiles in E. coli" Dr. Kelvin Lee, Chemical Engineering, Cornell University Biological systems manipulate gene expression in response to different
biochemical, environmental and genetic factors. Technology now permits the
genome-wide measurement of DNA sequence, mRNA expression levels and protein
expression levels. The relationship between measured changes in gene
expression at the mRNA level to the corresponding changes at the protein
level is not well understood. We have developed a mathematical framework
for gene expression at the genome-wide level that may be used to predict
protein expression profiles based on measured mRNA expression profiles and
DNA sequence information in Escherichia coli. Such a model could be used to
obviate the need to measure protein expression profiles in certain systems
when chip data is available. More importantly, a model can be used in
combination with mRNA and protein data to better understand gene expression
regulation. Our experiments using Affymetrix Genechip Probe Arrays and
protein two-dimensional gels and mass spectrometry provide allow us to test
model predictions and we have been able to predict qualitative changes in
gene expression (such as those that may arise from a limited number of free
ribosomes to engage in translation) and quantitative changes (such as
shifts in the mRNA-protein relationship for individual genes). We have also
used isobaric tags for relative and absolute quantitation of protein
expression to further validate the model.
March 8 , 2005 - Canceled
March 22 , 2005 - "Biotechnological approaches for clinical and basic research on fetal cells present in maternal tissue during and following pregnancy", Dr. Kirby Johnson, Tuft University, Boston
It has now been established that fetal cells cross into the maternal circulation during pregnancy. The ability to isolate rare fetal cells from maternal blood and use them as a noninvasive source of genetic information has been a long-sought goal of prenatal diagnosis. However, previous methods towards this goal have been unsuccessful due to the need to selectively isolate fetal cells from the much larger population of maternal cells in peripheral blood. Any efforts to decrease the numbers of maternal cells also resulted in the loss of fetal cells. Therefore, we have developed methods to exclusively isolate these rare fetal cells for clinical diagnostics without concomitant isolation of confounding maternal cells utilizing a novel microfluidics approach combined with various cell separation modules. In addition, fetal cells can persist in the maternal circulation and solid tissues long after pregnancy termination, in some cases for life. This long-term persistence has been termed “microchimerism.” The effect of persistent microchimeric fetal cells on maternal health is currently unknown. Due to numerous constraints for the study of microchimerism in humans, we have developed an animal model that involves the mating of wild type female mice with transgenic males. With this model, fetal cells can be identified in maternal tissue based on the inheritance of the paternally derived transgene sequence. Fetal cells can then be monitored in vivo based on the presence of the expressed transgenic protein, which is visualized utilizing novel imaging technology that produces visual and quantitative representations of biophotonic data generated within living organisms in real time. Downstream assessment of fetal cells for either prenatal diagnosis or studies of microchimerism includes fluorescence in situ hybridization, comparative genomic hybridization and polymerase chain reaction analysis of genomic DNA, gene expression profiling of mRNA using microarrays, and histochemical analysis of protein expression to characterize phenotype. Multidisciplinary approaches to the localization, isolation and characterization of fetal cells present in maternal tissue have been critical for the advancement of the fields of noninvasive prenatal diagnosis and fetal cell microchimerism. This talk will focus on the various technologies that have been developed and optimized towards the goal of understanding fetomaternal cell trafficking in terms of both basic research and clinical applications.
April 12 , 2005 -
"Microscale foundries for nanoscale synthesis and analysis", Vince Remcho, Ph.D., Chemistry, Oregon State University - A critical barrier to the routine use of nanomaterials is the tedious, expensive means of their synthesis. It is expected that the field of nanoproduction can be advanced using the improved process control made available within highly-parallel, process-intensified microsystems. Microsystems technology has the capacity to transform current batch nanoproduction practices into continuous processes with rapid, uniform mixing and precise temperature control. These same advantages extend to the assembly of microscale analytical systems for bioanalysis. Additional advantages of microsystems technology include eliminating air contact thereby minimizing contamination and improving yield; minimizing the environmental impact of nanoproduction including solvent free mixing, integrated separation techniques and reagent recycling; and the possibility of synthesizing nanomaterials in the required volumes at the point of use eliminating the need to store and transport potentially hazardous materials. A key requirement of this microsystems technology is the need for high-throughput extraction technology to minimize excess reagent and defective product to further improve yields in downstream reactions. In this presentation, progress is reported towards the development of high-throughput nanoextraction technology for implementation in microsystems. In particular, methods for production of monolithic, porous chromatographic supports in microfabricated fluidic pathways and the subsequent surface immobilization of a thrombin-binding aptamer* on the surface of the monolith are described. These sorbents are subsequently used in a novel nanoextraction technique. Implementation of the nanoextractor is within a stiff polymer sheet architecture with the capability to integrate pneumatic valves for injection and extraction. The fabrication architecture bears the added advantage of providing an economical pathway to “numbering up” for high-throughput production.
* Aptamers, oligonucleotides isolated and amplified based on their recognition of a target molecule, exhibit selectivites for their targets that rival those of antibodies yet are stable in a wide variety of chemical environments. This coupled with their small size makes them ideal candidates for affinity extractions.
April 26 , 2005 - "Chromatin Damage Induced by Carcinogenic Nickel Compounds". Dr. K.S. Kasprzak, Metals Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick , MD 21702 - The molecular mechanisms of nickel carcinogensis involve both genotoxic and epigenetic effects. Over the last years we have been testing a hypothesis that the mechanisms would include damage to major chromatin components such as DNA, histones, and protamines, mainly through direct Ni(II) interactions with the latter two. Our investigations led to identification of Ni(II)-binding amino acid motifs: -CAIH- in histone H3, -TESHHK- in histone H2A, and RTH- in protamine P2. Using peptide models, we determined structural and redox properties of Ni(II) complexes with these motifs. The Ni(II)-CAIH complex was redox-active and enhanced promutagenic oxidative DNA damage. In contrast, the Ni(II)-TESHHK- complex lacked redox activity. However, Ni(II) in the latter mediated hydrolysis of the peptide bond between the Glu and Ser residues, yielding a new redox-active Ni(II)-SHHK- complex. The hydrolysis of H2A at the –TESHHK- motif, resulting in the truncation of its C-terminal tail, was also observed in Ni(II)-treated cells in culture. Also in cells, but not in a test tube, Ni(II) was found to induce truncation of yet another histone protein, histone H2B. The binding to the N-terminal RTH- motif of protamine P2 enhanced Ni(II) capacity to mediate oxidative damage to the protamine itself and to DNA. In addition, we found a long-range structuring effect of Ni(II) coordinated by this motif on P2 folding in solution that explained alterations in P2 association with DNA and site-specificity of Ni(II)-dependent P2 oxidation. In conclusion, Ni(II) may be bound and redox-activated by some chromatin proteins, or their degradation products, in somatic and sperm cells. Bound Ni(II) may also enhance peptide bond hydrolysis. These effects, damaging to the molecular components and structure of chromatin, may alter the fidelity of DNA replication and gene expression, and thus facilitate carcinogenesis, including paternally-mediated cancer.
May 10, 2005 - Dr. George Spirou, Professor & Director, West Virginia University Sensory Neuroscience Research Center. "The Neural Encoding of Sound Location"
May 17, 2005 - Dr. Junfeng Liu, Yale Center for Statistical Genomics and Proteomics, Division of Biostatistics, Departmentof Epidemiology and Public Health, Yale University School of Medicine "Advances in Bioinformatics"
May 24 , 2005 - "On Molecular Ratchets, Kaleidocycles and Rings of Smoke" Dr. Igor Kulic, Department of Physics, University of Pennsylvania The emerging physical concept of molecular ratchets has brought unifying physical insights into many branches of molecular biology. It can be stated that essentially every active cellular process relies on an obvious or sometimes hidden action of a ratchet. After illustrating the ubiquity of various types of ratchets in cellular propulsion and intracellular transport we show how similar principles can be mimicked to devise artificial "low-tech" nanomachines. A surprisingly simple example for such an artificial device is a DNA miniplasmid. When properly excited by light or temperature oscillations its backbone starts to twirl in a ring of smoke fashion. The hydrodynamics of the ratcheting DNA ring leads to an efficient self-propulsion through the surrounding medium at several microns per second.
June 14 , 2005 - TBA
June 28 , 2005 - TBA
SYSTEMS BIOLOGY INITIATIVE SEMINAR COMMITTEE
If you would like to give a seminar, please contact
Dr. John Barnett,Director
WVU Systems Biology Initiative
WVU Chair, Microbiology, Immunology & Cell Biology
send mail to Dr. John Barnett
Dr. Lisa Holland
WVU Department of Chemistry
send mail to Dr. Lisa Holland
Dr. Leonardo Golubovic
WVU Department of Physics
send mail to Dr. Leonardo Golubovic
Dr. Dimitris Korakakis
WVU Department of Comp Science & Electrical Engineering
send mail to Dr. Dimitris Korakakis
WVU School of Agricultural Sciences
send mail to Dr. Joginder Nath
Dr. Raymond Raylman
Associate Professor Vice Chair for Research
Department of Radiology
send mail to Dr. Raymond Raylman
Dr. Tracy L. Morris
WVU Department of Psychology
send mail to Dr. Tracy Morris
Dr. Johnathan Cummings
WVU Chair, Biology
send mail to Dr. Johnathan Cummings
Dr. Dale Porter
National Institute of Occupational Safety and Health send mail to Dr. Dale Porter