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Intensive, Multidisciplinary Laboratory Training for Undergraduates
Summary: Winston Anderson's research concerns the development of synthetic oxygen transport media for blood volume replacement, and more recently, the subcellular localization of signal transduction activity for protooncogene proteins, growth factors and receptors, and binding proteins in prostate carcinoma and breast cancer cell lines and tissues. His HHMI project is an intensive program for honors biology or chemistry majors involving experimental research courses, a summer research program, a summer exchange program in several African countries, and a seminar series. Anchoring the program are two collaborative core labs in microscopy and biotechnology.
Project Summary
Our project involves a comprehensive research-oriented academic program that is designed to train and produce 100 undergraduates in four years with skills that will provide a competitive edge for entrance into graduate school and professional research careers in biomedical and related sciences. Each year, our project will target 20 freshmen and sophomores from a pool of more than 150 honors biology and chemistry majors. These students, Howard Hughes Research Scholars, will participate in experimental research courses that will provide intensive hands-on research in biomedical disciplines. The students will apprentice with research scientists in the departments of chemistry, biology, mathematics, physiology and biophysics, and in laboratories in the schools of engineering and medicine. They will work alongside mentors investigating nanofabricated structures and polymers, surface topography of nanomaterial/cell interfaces, and cell functions involving growth factors and signal transduction processes in cells, study of novel biocompatible nanoscale materials and devices for restoring bio-functions, and growth factors and oxidative stress that regulate cellular contact and tissue assembly in cell-materials interaction, and the ability to tailor the nano-materials so as to achieve the desired bioresponse. Trainees will benefit from tutoring and guidance through interaction with peer graduate student mentors.
Our project will also offer extensive summer research exposure through courses and workshops in laboratories at Woods Hole, the National Institutes of Health, Cold Spring Harbor, the Mayo Clinic, the University of Oklahoma, the University of Pittsburgh, Cornell Medical College, and Cornell University. In addition, students will have an opportunity to participate in extensive summer research exchange programs in infectious and tropical diseases (malaria, trypanosomiasis, leishmaniasis, schistosomiasis) and ethnopharmacology at universities in Ghana, Ethiopia, Mali, and Nigeria. Students will participate in annual scientific meetings, present papers, and submit manuscripts to peer-reviewed journals.
The program will also offer a monthly university-wide seminar series on contemporary biomedical topics. There is also the possibility of students participating in apprenticeships and/or graduate study in speakers' laboratories.
The technical expertise and infrastructure of the undergraduate research program will be enhanced through the establishment of two collaborative core laboratories (CCUs): a microscopy core equipped with photomicroscopes, fluorescence and confocal microscopes, and ultramicrotomes for electron microscopic preparation, and a biotechnology core to enhance biochemical, molecular biological, and cell culture activities. The CCUs will also facilitate and enhance training and research by physical and biological scientists from six departments and collaborators from Catholic University and Morgan State University. By pooling specialized skills and equipment in a user-friendly centralized facility, the nation's young scientists and engineers will recognize and understand fundamental phenomena at work through the convergence of live cellular with emerging nanotechnological systems. These CCUs will anchor the educational and training activities of the students.
Predoctoral students will serve as tutors and peers of undergraduate researchers. Gateway courses in cell, developmental, micro-, and molecular biology will be upgraded to prepare honors freshmen for entrance into the program. In addition, high school seniors with high SAT scores from regional science high schools will be chosen to take college courses and be introduced into the research-oriented academic pipeline.
Research Summary
We are among the first scientists to develop stroma-free hemoglobin (SFH) as a blood substitute and preservative for transplanted kidneys. We used mixtures of crystallized SFH and perfluorochemical emulsions (Fluosol-DA) as effective whole-blood substitutes that preserve the integrity of the kidney and normal glomerular filtration rate, and ameliorated the nephrotoxicity associated with Fluosol alone. The advances in synthetic oxygen transport media for blood volume replacement may have direct applications in organ transplant patients as well as survivors of catastrophic events.
More recently, our research has focused on the subcellular localization of signal transduction activity for protooncogene proteins, growth factors and receptors, and binding proteins in prostate carcinoma and breast cancer cell lines and tissues. We have established cocultures of prostate bone cells on a collagen matrix in order to understand the disease's pathophysiology and the regulatory roles of bone matrix proteins, other growth factors, binding proteins, and proteases.
Recent research has shown that carcinoma of the prostate (CaP) has an intact IGF (insulin-like growth factor)-IGFR (IGF receptor) axis, complete with cell cycle regulatory agents. Working through the IGF/IGFR axis, these regulatory agents drive the CaP cell toward either growth or apoptosis. IGFBP (IGF binding protein) -3 and -5 appear to be key regulators of the cell cycle control points in CaP and normal prostate.
IGFBP-3 dose-dependently induces apoptosis through the IGF/IGFR axis, indicating that decreased IGFBP-3 induces apoptosis. However, IGFBP-5 appears to be growth enhancing and is regulated by cytokines. The cytokines also seem to regulate the synthesis of IGFBP-3 protease (PSA), thus enhancing the IGF/IGFR mitogenic progression in prostate cells. Cotreatment with IGFBP-3 antibodies or antisense thiolated nucleotides blocks IGFBP-3 activity in PC-3 cells, enhancing the mitogenic progression. These studies indicate that the IGFBP-3/-R/protease axis plays a key role in the mitogenic/apoptotic decision in the CaP cell cycle.
Last updated September 2006
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