The placenta is the lifeline for mammalian reproduction and a complex organ that provides clues about natural selection and evolution.

Through phylogenetic analysis of molecular and anatomical data, researchers from Wayne State University and the Perinatology Research Branch (National Institute of Child Health and Human Development/National Institutes of Health) have presented evidence in the Feb. 28 issue of the Proceedings of the National Academy of Sciences describing the evolutionary history of the placenta of eutherian mammals — the group that includes all mammal species except marsupials and the egg laying monotremes (for example, the duck billed platypus). The authors conclude that the human placenta — although different from the ancestral type — resembles the original eutherian placenta in many aspects.

Early placental structures (existence of particular membranes) can be inferred from the fossil evidence of Ichthyosaurus, more than 170 million years ago. A variety of placenta-like structures are also found in squamate or scaly reptiles. The placenta allows live births, as opposed to hatching eggs, and gives mammals their place on the evolutionary tree.

In contrast to most theories, the PNAS authors say the disc-shaped, hemochorial placenta of many primates, including humans, existed throughout the eutherian lineage from the last common ancestor of placental mammals to the emergence of humans. These findings suggest that evolutionary pressures shaped mammal placentas to be an organ that must meet the demands of both the mother and the developing fetus during pregnancy.

Primary author Derek Wildman, Ph.D., assistant professor in WSU's Center for Molecular Medicine and Genetics and Department of Obstetrics and Gynecology and member of the Perinatology Research Branch, NICHD/NIH, says, in the past many biologists assumed that the placental structures of humans and other “higher” primates were advanced among mammals and other classes. This newly published evidence, however, reconstructs the ancestral eutherian placenta to be similar to the human placenta in terms of its disc-like shape and its ability to invade deeply into the maternal uterus (this maternofetal interface is called hemochorial in technical language). However, unlike the placentas of ancestral mammals, human placentas transfer nutrients, gases and other materials through a tree-like branching system of villi.

The placenta of marsupials (kangaroos and koalas, for example) is different than that of eutherians, because the presence of the placenta is very short-lived and contributes more to embryonic than to fetal nourishment. Differences and variations also exist within the eutherian group. For example, the placenta of rodents differs from primates in that rodent fetuses have a much shorter gestation and may use maternal resources at a more rapid rate. The evolution of the primate placenta required some changes necessary to sustain a longer pregnancy without depleting maternal resources and energy, the authors said.

The report, “Evolution of the Mammalian Placenta Revealed by Phylogenetic Analysis,” was contributed to the PNAS by Morris Goodman, Ph.D., WSU distinguished professor, who is a member of the National Academy of Sciences. It can be viewed online at: http://www.pnas.org/ . Co-authors are: Derek Wildman (WSU Center for Molecular Medicine and Genetics; Department of Obstetrics and Gynecology; Perinatology Research Branch, NICHD, National Institutes of Health); Caoyi Chen (WSU Center for Molecular Medicine and Genetics); Offer Erez (Perinatology Research Branch, NICHD, National Institutes of Health; WSU Department of Obstetrics and Gynecology); Lawrence I. Grossman (WSU Center for Molecular Medicine and Genetics); Morris Goodman (WSU Department of Anatomy and Cell Biology; Center for Molecular Medicine and Genetics); and Roberto Romero (Perinatology Research Branch, NICHD, National Institutes of Health; WSU Department of Obstetrics and Gynecology; Center for Molecular Medicine and Genetics).

“The effects of selection pressures on the efficiency of placentation may stem from changes in nutritional demand, gestational length, number of embryos per pregnancy, uterine shape and maternal body constitution,” Dr. Wildman said.

“There may be more variability in placenta structure than any other mammalian organ,” said Dr. Goodman. A pioneer of molecular phylogenetics, Dr. Goodman rocked the scientific world in 1962 by suggesting that gorillas and chimpanzees are more closely related to humans than to other great apes and monkeys. Throughout the decades, he and his colleagues have built substantial evidence to show that the DNA of chimpanzees and humans makes them more than 99 percent identical.

Interim Dean Robert Frank recently appointed Thomas Roe, M.D., as interim assistant dean for clinical science education, effective March 1.

Dr. Roe is a 1980 graduate of the Wayne State University School of Medicine and completed his family medicine residency at Providence Hospital. Following his training, he served as a National Health Service Corp. physician with Northern Michigan Health Services and later joined the Henry Ford Medical Group, where he served 16 years as a staff physician, advancing to medical director and physician-in-charge.

Dr. Roe returned to his alma mater in 2001 as assistant professor of family medicine and co-director of medical student education programs. Since his return to the school, Tom has led the required family medicine clerkship as well as the school's integrated clinical medicine course.

Dr. Roe is committed to high-quality, student-centered and innovative medical education programs. His research interests include the effective use of standardized patients in medical student education and the role of communication and the patient-physician interaction in reducing health disparities.

"I am confident that Tom's talent and skills; his many years of compassionate practice; and his experience in medical student education and research will substantially enrich our clinical science curriculum," Dr. Frank wrote in a letter announcing Dr. Roe's appointment.

Dr. Roe replaces Kenneth Ginsburg, M.D., who served in the role for five years. Dr. Ginsburg will return to the Department of Obstetrics and Gynecology, where he is an associate professor with a clinical specialty in reproductive endocrinology and infertility.

Sample some healthy – and delicious – soul food at a community event sponsored by the WSU Center for Urban & African-American Health Tuesday, Feb. 28, at the Charles H. Wright Museum of African-American History. The day's activities, which run from 4 p.m. to 7 p.m., also include discussion about the past, present and future of African-American research.

The event will also provide an opportunity to learn more about how to participate in groundbreaking new studies about African-American Health.

"African Americans comprise one of the largest minority groups in the United States , and they suffer excessively from a wide range of obesity and lifestyle-related health conditions," said John Flack, M.D., M.P.H., interim chair of the WSU Department of Internal Medicine and principal investigator for the Center for Urban & African-American Health. "We hope to alleviate the disproportionate burden of disease through better understanding of the precursors, and how their interactions cause disease. We can only do that with the help and participation of the community here in Detroit .”

The Center for Urban & African-American Health was one of eight centers established in the United States by the National Institute of Environmental Health Sciences to study population health and health disparities

Dr. Flack, who has published extensively on African Americans' salt sensitivity and predisposition to hypertension, understands the unique health needs of the population to which he refers and belongs. As a professor of internal medicine and community medicine, he sees the immediate link between a person's individualized health concerns and those they are automatically subjected to by virtue of their geographic location, gender, age, race or ethnicity.

To help understand these concerns, the center is working on several studies, including two that are seeking people from metro Detroit to participate in non-invasive activities to determine how various lifestyle factors impact health.

The first study seeks to understand social and physical factors in African Americans to provide insight into prevalent health issues. Participants must be African American, 45 years or older, 60 to 100 pounds overweight and without blood pressure or diabetes.

The second study seeks to evaluate the possible health benefits of weight loss in African-American women who have had stage I or II breast cancer. Participation in this study aids in research on the prevention of breast cancer recurrence. Women who are African American, 18 to 70 years of age and have had stage I or II breast cancer diagnosed within the past three years are needed. Participants must have finished all chemo or radiation therapy at least three months prior to enrolling in the study and must be 30 to 100 pounds overweight and willing to follow a weight-loss plan for 24 months.

More information about these studies as well as talks by Mary “Toni” Flowers, R.N., director of MPRO; Linda Herskovitz, WSU community outreach and education liaison; and Marilyn Anderson, R.D., a dietician and diabetes educator, will be available at the community event Feb. 28. In addition, cooking demonstrations on how to prepare healthy, delicious soul food will be available. “Mother's Love Catering” will be providing food for the event.

Members of the public who are interested in receiving more information on this event or current studies underway at the center, please call Donna Ford at (313) 745-5774.

Find out what's driving up pharmaceutical costs at WSU seminar series on medical, genetic controversies

Prescription drugs aren't cheap – nor are the lives they can save. Pharmaceutical companies walk a precarious line between financial interest and social mission – a line that begins in the laboratories of university researchers.

The Center for Molecular Medicine will tackle tough questions about why drug development is expensive at the second session of its provocative seminar series on controversial issues in molecular medicine on Friday, Feb. 24. Hosted by the Wayne State University Center for Molecular Medicine and Genetics and open to the public, the “Hot Topics in Molecular Medicine” series offers a forum for discussion on a number of issues that apply to everyday living.

This seminar will look at the full story behind a new drug; the pharmaceutical companies are the most obvious characters in the plot, but universities, scientists, physicians, government agencies, patients and consumers play significant roles. Jeffrey A. Loeb, M.D., Ph.D., WSU associate professor of neurology and molecular medicine & genetics, will lead participants through the maze of drug development, discussing hurdles faced in developing and commercializing a new drug for cancer treatment.

By the end of the talk, the real cost of drug development – and who pays for each step along the way – will be apparent.

Questions and debate are encouraged. All participants are invited to continue the discussion with faculty and physicians over food and beverage at a reception immediately following.

“How to Make a New Drug: Using Brains to Treat Breast Cancer” will be at 4 p.m., Friday, Feb. 24, in Jaffar Auditorium, Scott Hall, 540 E. Canfield, Detroit . Complimentary valet parking will be provided at the University Health Center Garage, off of St. Antoine, just south of Canfield.

Phylogenetic comparisons suggest that the locus control region (LCR)—the area that regulates transcription—interacts with primate ß-type globin genes to mediate different developmental expression patterns in different branches of the evolutionary tree. The primates more distantly related to humans, prosimians (like the African Bush Babies) and New World monkeys (flat-nose monkeys with prehensile tails), express embryonically the ? globin gene neighboring e. In contrast, catarrhines (Old World monkeys and apes, including humans) express these genes primarily during fetal development.

The globin genes, labeled e, ?, ??, d, ß, fall into a cluster in this order located just downstream of the LCR. A short distance between e and ? allows the LCR to drive embryonic expression in both genes, whereas a longer distance impedes embryonic activation of the downstream gene.

A report in the February 14 issue of the Proceedings of the National Academy of Sciences uses phylogenetic reconstructions to show that in prosimians, the LCR acts to fully turn on a single ? gene along with e during embryonic life and then repressors act to shut both genes off at the beginning of fetal life at which time the LCR acts to fully turn on the d and ßgenes. In simian primates, with their duplicated ? games, two distinct patterns are seen: in New World monkeys, the ? gene closest to the LCR is predominantly embryonically expressed, whereas in catarrhines, it is predominantly fetally expressed. Furthermore, in New World monkeys, the ? gene furthest from the LCR is the major fetally expressed gene, whereas in catarrhines, it is the ? gene closest to the LCR that assumes this pattern. These differences can be attributed to the varying distances of these genes from the LCR: in New World monkeys, the first ? gene is approximately 6-7 kb from e, whereas in catarrhines, it is 13-14kb.

The article is authored by Robert Johnson, Ph.D., professor of biochemistry and molecular biology at Wayne State University, and was contributed by Morris Goodman, Ph.D., distinguished professor, who is a member of the National Academy of Sciences. The full article, “Phylogenetic Comparisons Suggest That Distance from the Locus Control Region Guides Developmental Expression of Primate ß-type Globin Genes,” can be viewed online at: http://www.pnas.org/ . Co-authors are: Tom Prychitko, Deborah Gumucio, Derek Wildman and Monica Uddin.

“Our approach is to examine the hemoglobin changes in primate species closely related to humans, in which the switching program is subtly different. By examining promoter regions from genes that turn on at different points in embryogenesis, we are able to pinpoint promoter changes that mediate the timing of the developmental switch,” Dr. Johnson said.

During embryonic life, ? and a genes switch on to encode a-type chains and the e gene switches on to encode ßtype chains. At about the sixth to eighth week of prenatal life—approximately the beginning of the fetal period—the ? and e chains switch off. In higher primates, the a genes remain on, but as the e gene switches off, the two ? genes switch on. By contrast, there is only one ? gene in tarsiers (the small nocturnal arboreal primates with large round eyes and a long tail), but the γ gene is duplicated in simians.

Past collaborations among Drs. Johnson, Goodman and their colleagues have revealed that e, the gene at the beginning of the globin cluster, had all the regulatory sequences that would characterize an embryonically expressed gene. The downstream ßgene had all the regulatory sequences for a post-embryonically expressed gene. These results have been confirmed in Australian marsupial mammals, where the e gene remains embryonic for about a day as the embryo migrates to the pouch, rapidly becomes fetal and then postfetal. After the one day migration, the e hemoglobin gene is turned off and the ßgene is turned on. Regulatory sequences in the proximity of each of the two genes play key roles in the switching, although the mechanism was not well understood until this publication that reports the importance of the LCR, whose relative distance can greatly enhance expression of each functional gene at the appropriate developmental stage.

These results reveal more than the complexity of factors regulating developmental expression patterns in primate ß-type globin genes. They also provide treatment clues for hemoglobinopathies like sickle cell anemia and thalassemia . “We want to put our finger on those cis-regulatory elements that are part of the ancient machinery of hemoglobin switching and those cis-regulatory elements that are part of the recent machinery that causes these ? genes not to be expressed in embryonic life but rather fetal life. If we could understand the elements that control the expression of the ? gene, then we could play around with how to manipulate these elements so that we can get the ? gene expressed after birth for patients with hemoglobinopathies,” Dr. Goodman said.

This work is supported by the National Institutes of Health and the National Science Foundation.

 

Everybody knows somebody who is touched by cancer and everybody seems to have lots of questions about the causes, cures and treatments for the disease. Through his national service to the National Cancer Institute, Dr. Richard Gallagher is helping to provide the most accurate cancer information and educational resources to physicians, health professionals and the general public—a hectic responsibility in the ever-advancing field of cancer research.

Richard E. Gallagher, Ph.D., Wayne State University professor of family medicine, has accepted an invitation to chair the National Cancer Institute Subcommittee G-Education. Subcommittee G sets the scientific and research agenda for cancer education by reviewing training grants, proposed curricular programs and career development applications for scientists and health administrators around the country.

Dr. Gallagher, who is director of the Division of Medical Education in the Department of Family Medicine and adjunct professor at the Barbara Ann Karmanos Cancer Institute, is no stranger to National Institutes of Health study sections, having served on them continuously for more than 25 years. He has had a career-long interest and involvement in cancer education at Wayne State University School of Medicine and at the national level. He is an active researcher in the WSU/Karmanos Population Studies and Prevention Program and he is interested in physician training and community health education.

Dr.Gallagher is a pioneer in the teaching of cancer prevention concepts and skills to undergraduate medical students. He has served as the principal investigator on one of five national contracts that was funded in 1979 by the National Cancer Institute to test the feasibility of teaching cancer prevention to U.S. medical students. He is a lifetime fellow and recent past-president of the American Association for Cancer Education.

“Dr. Gallagher is not only a pioneer in the content area of cancer prevention and education, but he has also set the gold standard in delivery methodology and evaluation of education interventions. Ultimately, physicians, patients and communities want to use--and fund--what works. Dr. Gallagher has demonstrated the effectiveness of both new and established cancer education programs and has extended our knowledge to include testing of these programs in diverse populations,”said Maryjean Schenk, M.D., WSU chair of family medicine.

In the letter of invitation sent to Dr. Gallagher, Sonya V. Roberson, Ph.D., the National Cancer Institute scientific review officer assigned to Committee G, noted that Dr. Gallagher was selected for this role because of his particular expertise and insights in methods of learning, instruction, curriculum development, program, evaluation, cancer prevention and community health. Dr. Roberson further noted that the position of study section chair that Dr. Gallagher has accepted will provide him an “incomparable overview of cancer research in educational programs in the United States and will provide an opportunity to shape the nature of cancer education grant reviews.”

 

Dr. Hendrix leads study at WSU School of Medicine

A major study including nearly 50,000 women followed over eight years indicates that a diet low in fat, but high in fruit, vegetables and grains, does not significantly reduce the risk of breast cancer, colorectal cancer or cardiovascular disease in postmenopausal women, according to a study published in the Feb. 8 issue of JAMA by Susan Hendrix, D.O., WSU professor of obstetrics and gynecology, and her colleagues in the National Institutes of Health Women's Health Initiative.

“This is not permission to go to your local fast food restaurant and eat anything you want," Dr. Hendrix said. "But this study shows us that a low-fat diet is not going to be able to reduce risk."

The Women's Health Initiative Dietary Modification Trial examined the effect of a low-fat diet on the incidence of breast cancer. The WHI, which began in 1992 with 48,835 postmenopausal women without prior breast cancer, included a dietary modification intervention consisting of consumption of a reduced amount of fat (20 percent of energy) and of an increased amount of vegetables and fruits (5 or more servings a day) and grains (6 or more servings a day). The women, aged 50 to 79 years, were randomly assigned to the dietary modification intervention group (40 percent, or 19,541) or the comparison group, who were not asked to make dietary modifications (60 percent, or 29,294). It has been hypothesized that a low-fat diet can reduce breast cancer risk, but previous studies have had mixed results.

The average follow-up time was 8.1 years. Overall, 655 (3.35 percent) women in the intervention group and 1,072 (3.66 percent) women in the comparison group developed invasive breast cancer during follow-up.

The researchers found that there were 201 cases of invasive colorectal cancer (0.13 percent per year) in the intervention group and 279 (0.12 percent) in the comparison group. The WHI low-fat eating pattern intervention did not reduce the risk of invasive colorectal cancers. There was no evidence of reduced risk for any category of colorectal cancer outcome associated with the intervention.

Levels of low-density lipoprotein cholesterol and diastolic blood pressure were significantly reduced. Levels of high-density lipoprotein cholesterol, triglycerides, glucose and insulin did not significantly differ in the intervention vs. comparison groups. The researchers found that the diet had no significant effects on incidence of coronary heart disease, stroke, cardiovascular disease or heart attack. Trends toward greater reductions in coronary heart disease risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.

For more information or to read the study, please visit http://jama.ama-assn.org/cgi/content/full/295/6/629.

 

Joe Montana, NFL Hall of Fame quarterback, will bring a little bit of Super Bowl XL excitement to the WSU School of Medicine/Detroit Medical Center campus on Thursday, Feb. 2. Mr. Montana will talk with Detroit police, fire and EMS workers about the importance of staying healthy and keeping their blood pressure in check. Mr. Montana is a spokesperson for the pharmaceutical company Novartis's blood pressure control program.