RESEARCH PROFILES these proteins, physicians may be able to distinguish women who will give birth early from those who will deliver at term. The proteins that were differentially regulated could shed light on the biology of PTL and SPTB. SPTB is often considered as a single process, says Gravett, but studies such as theirs reveal that many pathways may be involved. Calgranulins, which were upregulated in PTL and SPTB, are associated with infection or inflammation, which is a known cause of SPTB. Other markers, such as insulin-like growth factor binding protein-1 (IGFBP-1), are known to be abundant in the amniotic fluid. “So when we see IGFBP-1, it may
indicate that there’s a leakage of the amniotic membranes,” says Gravett. Fibronectins hold the amniotic membranes to the wall of the uterus, so the presence of these proteins in the CVF of SPTB women may reflect a mechanical disruption. In addition, low levels of cytoskeletal proteins were correlated with SPTB. “Cytoskeletal proteins could relate to the cervical changes that are occurring during the process of labor,” says Nagalla. Although the researchers have found some potential biomarkers for PTL and SPTB, they say that a lot of work lies ahead. “We have initiated a multicenter prospective study to enroll women [who are] in PTL and SPTB so that we
can measure these analytes, do a statistical analysis, and identify the sensitivity and specificity of each marker,” says Nagalla. In the next set of studies, they plan to focus on four categories of markers: CVF proteins that are abundant in amniotic fluid and could have leaked from the amnion, those that are indicative of infection, proteins that are unique to CVF, and acute-phase response proteins that are involved in the labor process. “I think we can also use proteomics technology to help identify pathway-specific mechanisms of SPTB, and it’s my dream that the results will suggest pathway-specific treatments or interventions,” says Gravett. —Katie Cottingham
PROTEOMICS PROJECTS
HUPO Cardiovascular Initiative comes into its own
that some of our problems are unique.” Unlike with cancer, patients typically struggle with cardiovascular disease for the rest of their lives, says Ping. “We don’t have a cure; we have a way to control and modulate the phenotype,” she says. “These issues demand a different set of markers compared with other diseases.” For example, a patient
The HUPO Cardiovascular Initiative (CVI) officially became a freestanding HUPO initiative at the organization’s Fifth World Congress at Long Beach, Calif., in October 2006. For a year, the initiative had been part of HUPO’s Disease Biomarker Initiative, but its ~110 participants soon felt the group was ready to strike out on its own. Peipei Ping, who is at the David Geffen School of Medicine at the University of California Los Angeles and is chair of CVI, says that the Disease Biomarker Initiative was a good place to learn the ropes, but CVI particiMatters of the heart. HUPO CVI has become its own initiative. pants didn’t want to limit the focus to biomarkers. So Ping and cochairs Peter Liu of the with hypertension may take medicaCanadian Institutes of Health Research tion for the condition for 20 or 30 years. and Mike Dunn of University College The results of CVI research, therefore, Dublin reestablished CVI as a separate could help investigators to monitor a entity from the Disease Biomarker patient’s progress over the years or to Initiative. Spinning off allowed them tailor therapies. to broaden their scope. “There was a Because CVI is a clinically oriented demand for further growth, as well as a group, participants are very interested need to enhance our ability to accomin the education and training of the modate physicians and investigators next generation of physicians and in the cardiovascular community both physician-scientists. Ping says that, so with and without a biomarker focus,” far, only small pockets of clinicians are says Ping. aware of proteomics. She predicts that In addition, Liu says, “We realized in ~20 years, tests based on proteomics
1242 Journal of Proteome Research • Vol. 6, No. 4, 2007
techniques will become more commonplace, and everyone will benefit if clinicians understand how these tests work. Ping says that the training could be incorporated as part of physicians’ continuing medical education (known as CME). The overall goal of CVI is to discover the biological pathways involved in the disease and to identify potential biomarkers, says Liu. CVI researchers are not limiting themselves to proteomics techniques to reach these goals, however. According to Liu, some are pursuing metabolomic strategies, whereas others are working on gene expression and genomics projects. Researchers also are interested in standardizing sample collection and processing so that experiments can be compared across groups. Setting up CVI has gone smoothly, says Ping. Participants are discussing how to form working groups and are meeting often to stay in touch. Liu says, “The exciting thing is that once you bring a group of people together, you realize that the initiative has a life of its own that’s beyond any individual person’s ability to bring about change.” —Katie Cottingham
