Silver-Russell Syndrome

RECOGNIZED FOR DISCOVERIES IN GENE IMPRINTING & IMPACT OF ENVIRONMENTAL EXPOSURES ON PREGNANCY, PRENATAL DEVELOPMENT ARLINGTON, Va., Jan. 18, 2024 /PRNewswire/ -- March of Dimes, the leading organization fighting for the health of moms and babies, is pleased to announce Marisa Bartolomei, PhD, as the recipient of the 2024 March of Dimes Richard B. Johnston, Jr., MD Prize. This annual award honors an outstanding scientist who has advanced the science that underlies our understanding of pregnancy, birth, and prenatal development. Dr. Bartolomei is a Co-Director of the Epigenetics Institute at the University of Pennsylvania's Perelman School of Medicine, where she is also the Perelman Professor of Cell and Developmental Biology. Continue Reading Marisa Bartolomei, PHD Over her 30-year career, Dr. Bartolomei has made instrumental discoveries on the function and expression of certain genes, called imprinted genes. These genes, whose proper expression is critical for healthy pregnancy and fetal development, can be severely affected by numerous factors, including environmental exposures throughout life and pregnancy. "Dr. Bartolomei's astounding body of work on how the abnormal expression of imprinted genes can lead to severe developmental errors and devastating diseases for babies has brought us closer to the development of critical diagnostic and therapeutic interventions," said Dr. Emre Seli, Chief Scientific Officer at March of Dimes. "I am incredibly excited and honored to present Dr. Bartolomei with this award. She exemplifies the spirit of the prize through her dedication to bridging the divide between science at the bench and medicine at the bedside so the work we do today can improve outcomes for moms and babies tomorrow." This award, named in honor of Dr. Johnston, Professor Emeritus of Pediatrics at the University of Colorado and a former Medical Director at March of Dimes, carries a cash award and was created as a tribute to Dr. Jonas Salk, developer of the polio vaccine. It is part of March of Dimes' research strategy to address the multi-faceted nature of the maternal and child health crisis. To date, six recipients have gone on to win the Nobel Prize in Physiology or Medicine. Throughout her career, Dr. Bartolomei's research has addressed the epigenetic mechanisms of genomic imprinting and germline reprogramming as well as the impact of early environmental exposures on epigenetic gene regulation. Imprinted genes, unlike traditional genes, normally express only one copy (one from the mother or one from the father). When things go wrong, as with an epigenetic mutation, these genes will express either both or neither of its copies. This can cause devastating developmental errors during pregnancy that lead to serious disease. Dr. Bartolomei succeeded in identifying one of the first imprinted genes in 1991. Her later work identified connections between imprinted genes and early developmental disorders like Beckwith-Wiedemann Syndrome, which causes babies to grow too big in the womb and predisposes them to cancer, and Silver-Russell Syndrome, which causes babies to grow too slowly in utero. Her continued work in other related areas has improved our understanding of gene reprogramming, defects in expression, and the impact of environmental exposures, like Bisphenol A (BPA) and phthalates, on healthy development. This work has revealed the critical role of imprinted genes in healthy development, opening new possibilities to prevent and cure disease. "We are truly just getting started with imprinted genes," Dr. Bartolomei said. "As the scientific community continues to discover the vital role these genes have in development, others are doing work on new screening tests, therapeutics, and interventions to ensure that imprinted genes are expressed properly, and if they are not, to invent treatments that can be administered to avoid the worst outcomes. And for me, this award is truly exhilarating—when I look at past awardees, some of whom have been important mentors and influenced my career, it's really special." March of Dimes will present the award to Dr. Bartolomei at the 2024 Annual Meeting of the Society for Reproductive Investigation in Vancouver, British Columbia on March 16, 2024. Dr. Bartolomei received her BS from the University of Maryland and PhD from the Johns Hopkins University School of Medicine. She completed postdoctoral training at Princeton University with Dr. Shirley Tilghman, President Emerita Princeton University. In 1993, Dr. Bartolomei was appointed as Assistant Professor at the University of Pennsylvania, rising to Professor in 2006. She was elected as a Fellow of the American Association for the Advancement of Science in 2014 and is a Member of the National Academy of Sciences. Find more information about the Prize here. About March of Dimes March of Dimes leads the fight for the health of all moms and babies. We support research, lead programs, and provide education and advocacy so that every family can have the best possible start. Building on a successful 86-year legacy, we support every pregnant person and every family. To learn more about March of Dimes, please visit marchofdimes.org. SOURCE March of Dimes Inc.

Scientists have identified a key part of a mechanism that annotates genetic information before it is passed from fathers to their offspring. The findings shed new light on genomic imprinting, a fundamental, biological process in which a gene from one parent is switched off while the copy from the other parent remains active. Errors in imprinting are linked to a host of diseases, such as the rare disease Silver-Russell syndrome along with certain cancers and diabetes. Van Andel Institute scientists and collaborators have identified a key part of a mechanism that annotates genetic information before it is passed from fathers to their offspring. The findings, published today in the journal Science Advances, shed new light on genomic imprinting, a fundamental, biological process in which a gene from one parent is switched off while the copy from the other parent remains active. Errors in imprinting are linked to a host of diseases, such as the rare disease Silver-Russell syndrome along with certain cancers and diabetes. "Proper imprinting is crucial for lifelong health but, despite its importance, we still lack a full understanding of the factors that regulate this vital process," said VAI Associate Professor Piroska Szabó, Ph.D., the study's corresponding author. "Our findings reveal an RNA mechanism that governs establishment of imprinting and illuminates why it differs between fathers and mothers." Our genetic information is encoded in DNA, a long, winding molecule that is tightly packed to form 23 pairs of chromosomes, half of which come from one's father and half from one's mother. Sperm and eggs only contain 23 single chromosomes -- half of the genetic material required for life. During fertilization, they each contribute their half, resulting in a zygote with a full set of 23 pairs of chromosomes. But not all instructions in DNA are needed at the same time or in the same places. That's where epigenetics come in. Epigenetic mechanisms annotate DNA with special chemical tags called methyl groups, which tell certain genes when to be active and when to be silent -- all without changing the sequence of DNA itself. Imprinting occurs when methyl groups are added to certain genes during either sperm or egg formation. This, in turn, is important for determining which parental copy of that gene is expressed in the offspring. To better understand the processes that govern imprinting, Szabó and colleagues focused on an imprinting control region in the DNA that regulates the Igf2 gene. Igf2 plays key roles in fetal growth and only is active in the chromosome inherited from the father. Too little methylation in the IGF2 control region in humans can result in Silver-Russell syndrome, which is marked by reduced growth and increased risk of metabolic disease. "If the IGF2 gene's imprinting control region from one's father is not methylated, it can result in disease," Szabó said. Using genetic models and in-depth genetic sequencing, the team found that the methylation of the Igf2 control region in paternally inherited DNA is governed by an underlying RNA-based process in the male germline. "We found earlier that RNA similarly runs through other paternally marked imprinted domains in the male germ cells, suggesting that this same process is generally true for paternal imprinting," Szabó said. "These results suggest a more broadly applicable process, which is exciting and will need to be confirmed in subsequent studies." Other authors include Ji Liao, Ph.D., Zhen Fu, Ph.D., Ivan VanderKolk, Brianna M. Busscher and Kin H. Lau, Ph.D., of VAI; Sangmin Song of City of Hope Cancer Center; and Samuel Gusscott, Ph.D., and Julie Brind'Amour, Ph.D., of Université de Montréal.