Intensive, Multidisciplinary Laboratory Training for Undergraduates
Summary: Winston Anderson's Howard Hughes Medical Research Scholars program selects talented science and math majors and immerses them in a research-intensive, mentored curriculum designed to give them a competitive edge for pursuing Ph.D. degrees in the biomedical and related sciences. New initiatives will upgrade the science and mathematics curricula, incorporate more interdisciplinary courses, and offer double majors.
Howard University, a historically black university, is the leading producer of undergraduates from underrepresented minority groups who go on to pursue doctoral degrees in science, technology, engineering, and mathematics (STEM) disciplines. To build on this track record, we established the Howard Hughes Medical Research Scholars (HHMRS) program in 2006 with my HHMI professor funding. This research-intensive initiative is designed to attract more Howard premed students to research careers and give them a competitive edge when applying to top-tier graduate schools. From 2006 to 2009, 16 students have joined the program.
We identify the brightest freshman and sophomore honors science students and place them in research courses and apprenticeships in Howard research laboratories. The students attend workshops at Howard and several partner universities on contemporary biomedical research topics. A monthly seminar series with Nobel laureates and other distinguished scientists enables students to meet leading scientists in STEM fields. The students are also encouraged to present papers and posters at national meetings, such as the American Society for Cell Biology and the American Society for Microbiology.
We have formed alliances with the Massachusetts Institute of Technology (MIT), Cornell University, Harvard University, and the University of Wisconsin-Madison to provide opportunities for HHMRS scholars to spend summers in top research labs. From 2006 to 2009, 16 scholars participated. In addition, scholars can join exchange programs that allow them to study infectious and tropical diseases at universities in Ghana, Ethiopia, Mali, Nigeria, Tasmania, and Thailand. From 2006 to 2008, 11 scholars studied abroad.
One indicator of the program's success is the number of HHMRS students who received HHMI Gilliam Fellowships or were admitted to selective Ph.D. programs and M.D./Ph.D. programs. Since 2006, our HHMRS program has had ten graduates, eight of whom have entered graduate or M.D./Ph.D. programs in STEM fields. Three HHMRS scholars participated in HHMI Exceptional Research Opportunities Program as undergraduates, and one of these was awarded a prestigious Gilliam Fellowship for Advanced Study.
With our new grant, we will continue to identify talented freshmen and sophomores for the program and place them on an accelerated research and curricular pathway. But now, HHMRS biology majors will be expected to minor in chemistry or mathematics, while chemistry, mathematics, and physics majors will be encouraged to minor or double-major in biology. We will continue our association with MIT, Cornell, and other top research universities and expand the summer research opportunities for HHMRS students on those campuses.
The HHMRS students will enroll in new interdisciplinary courses that emphasize problem solving and critical thinking and convey the connections between the disciplines. We will offer new gateway courses in biochemistry and biomathematics and introduce advanced courses in nanosciences, computational mathematics, environmental sciences, genomics, and microbiology. We anticipate that the emphasis on mathematics and computational biology will increase students' competitiveness when applying for graduate school. We will continue previous efforts to incorporate computational instruction in beginning biology courses.
We think that first-rate teaching will go far to increase the number of underrepresented minority students pursuing graduate degrees in the biomedical sciences. So we will hold molecular biology workshops for Howard's STEM faculty and offer short- and long-term courses at Howard taught by STEM scientists from Cornell and other universities on genetics, biochemistry, molecular biology, and other topics. We also plan to deliver STEM instruction and research opportunities to students in science high schools on Washington, D.C. and in the Howard University Middle School of Science.
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.