Preventing Preterm Birth Initiative Projects

Round 1 grantees: 

Round 2 grantees:

Round 3 grantees:

Kristina Adams Waldorf, MD, and David Eschenbach, MD

PROJECT

Kristina Adams Waldorf, MD, and David Eschenbach, MD, at the University of Washington, will determine the effect of disturbances in the vaginal microbiome on preterm birth. Their research will investigate how specific vaginal bacterial infections and changes in the female reproductive tract are associated with preterm birth. The long-term goal is to identify new ways for early identification and treatment of women at risk of preterm birth and develop a point-of-care diagnostic test appropriate for low-resource settings, which would function much like a home pregnancy test, indicating an elevated risk of premature birth. Results could be imaged using a cell phone, sent to the laboratory, and results returned by text messages.

BIOS

Kristina Adams Waldorf, M.D. is an Associate Professor in the Department of Obstetrics and Gynecology at the University of Washington School of Medicine. She received a baccalaureate cum laude at the University of Washington and a medical degree from Mayo Medical School. She then completed a residency in Obstetrics & Gynecology at the University of Washington. In 2002, she began to study preterm birth and how to improve pregnancy outcomes.

Her research has focused on the connection between preterm birth, infection, immune responses in the placenta and fetus, and uterine stretch. She has won awards for her work investigating the earliest immune and biological responses to infections in the uterus and for testing possible therapies to prevent preterm birth. She has also studied how tolerance to the fetus is achieved during pregnancy and the long-term effects of maternal-fetal cell trafficking on the mother’s immune system. Dr. Adams Waldorf has been supported by the National Institutes of Health, the March of Dimes, Washington State Obstetrical Association, and the Global Alliance to Prevent Prematurity and Stillbirth.

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David A. Eschenbach, M.D. is Professor and Chair of the Department of Obstetrics and Gynecology at the University of Washington. He received a BA degree from Lawrence College and a medical doctor degree from the University of Wisconsin. He completed both a residency in obstetrics and gynecology and a fellowship in infectious diseases at the University of Washington before joining the faculty.

His research has focused on a wide variety of infectious diseases among women, including vaginitis, salpingitis, endometritis, both postpartum and in the non-pregnant woman and on potentially lethal infections. He also has published on the effect of amniotic fluid infection on the neonate. Most recently, his research has focused on the impact of vaginal, amniotic fluid and chorioamnion infections on preterm birth. Dr. Eschenbach has had research support from the National Institutes of Health, and the Global Alliance to Prevent Prematurity and Stillbirth.
 

David M. Aronoff, MD

PROJECT

Dr. David Aronoff of Vanderbilt University Medical Center, with an interdisciplinary team of experts in microbiology, immunology, reproductive biology, and vaccine development, will examine how infections of the female reproductive tract interact with and evade the immune system, resulting in infections of the uterus that cause preterm birth and stillbirth. This work will research potential targets for prevention of invasive infections of the female genital tract, including plans to investigate strains of group B Streptococcus (GBS) from low-income countries for vaccine and drug development.

Press release: Innovative research projects aims to prevent preterm birth
Publication: Pilus distribution among lineages of group b streptococcus: an evolutionary and clinical perspective. BMC Microbiology, 2014.
Dr. Aronoff's initiative was also selected for a Vanderbilt award, a good example of leveraging the PPB award and advancing cross-disciplinary science in preterm birth. 

 


BIO

David M. Aronoff, MD is an Associate Professor and the Director of the Division of Infectious Diseases within the Department of Medicine at Vanderbilt University Medical Center. He is also a faculty member within the Department of Pathology, Microbiology and Immunology at Vanderbilt. Dr. Aronoff earned his baccalaureate in Microbiology from Indiana University and a medical degree from Tufts University. He then completed a residency in Internal Medicine at Vanderbilt University, remaining there to conduct a clinical Infectious Diseases fellowship and a postdoctoral research fellowship in Clinical Pharmacology. In 2002, Dr. Aronoff moved to the University of Michigan for a postdoctoral fellowship studying innate immunity. He remained there and developed his research interest in reproductive immunology and infections complicating pregnancy. Dr. Aronoff also served as a member of the Executive Committee of the Reproductive Sciences Program at the University of Michigan.

In 2013, Dr. Aronoff was recruited back to Vanderbilt University to lead the Division of Infectious Diseases and create new programs that address the intersection of reproductive health and infectious diseases. The major research focus of the Aronoff lab is reproductive immunology, with a special interest in understanding how bacteria escape immune defense mechanisms to cause infections within the uterus during pregnancy.  

Nationally, Dr. Aronoff is an active member of the Infectious Diseases Society of America, the Anaerobe Society of the Americas, the American Society of Reproductive Immunology, and the American Society for Microbiology. His research has been supported by the Doris Duke Charitable Foundation, the Burroughs Wellcome Fund, the Central Society for Clinical Research, and the National Institutes of Health.


Margaret K. Hostetter, MD

PROJECT

Dr. Margaret Hostetter from Cincinnati Children’s Hospital Medical Center and her co-investigators will examine how disruption of the normal bacteria and other micro-organisms (the microbiome) of the lower female genital tract may increase risk of preterm birth. These investigations will focus on vaginal Candida infections in pregnancy, inflammation, and regulation of the immune response. Research will be conducted using animal models and laboratory investigations connected to studies of women in low-resource countries. Their goal is to investigate protective and pathogenic mechanisms of preterm birth and identify novel treatment strategies for vaginal fungal infections to prevent preterm birth.
 


BIO

Dr. Margaret K. Hostetter came to Cincinnati Children’s Hospital Medical Center in September 2010 as the Albert B. Sabin Professor of Pediatrics and Director of the Division of Infectious Diseases. On July 1, 2014 she became the B.K. Rachford Professor and Chair of the Department of Pediatrics and Director of the Cincinnati Children’s Research Foundation. Her research focuses on the yeast Candida albicans, a cause of vaginal colonization in pregnant women and of potentially fatal bloodstream infections in premature infants and other hosts. 

An Ohio native and graduate of Denison University, Dr. Hostetter earned her M.D. from Baylor College of Medicine in Houston, Texas, and completed her pediatric residency and fellowship in pediatric infectious diseases at Children's Hospital Boston. She has served as the American Legion Heart Research Professor in Pediatrics at the University of Minnesota and as the Jean McLean Wallace Professor of Pediatrics and Chair of the Department of Pediatrics at Yale before coming to Cincinnati Children's.

Dr. Hostetter's honors include the American Academy of Pediatrics Award for Excellence in Research, the Samuel Rosenthal Award for contributions to academic pediatrics, the E. Mead Johnson Award for Pediatric Research from the Society for Pediatric Research, and the Maxwell Finland Lecture from the Infectious Diseases Society of America. She is a member of the Institute of Medicine of the National Academy of Sciences.  


Kevin C. Kain, FRCPC, MD

PROJECT

Dr. Kevin Kain of the University Health Network and the University of Toronto will be investigating malaria infections of the placenta to reveal specific roles of the immune response that lead to preterm birth, low birth weight, and stillbirth. This project will focus on discovering biomarkers to identify at-risk pregnancies as well as new interventions to prevent adverse pregnancy outcomes.

Press release: Study Suggests Infant Deaths Can Be Prevented
Press release: Dr. Kevin Kain Wins International Funding Award
 


BIO

Kevin C. Kain, FRCPC, MD, is the Director, Sandra Rotman Laboratories for Global Health, Director, Tropical Disease Unit, Toronto General Hospital, a Professor of Medicine at the University of Toronto, and holds a Canada Research Chair. Dr. Kain received research training at the Walter Reed Army Institute of Research and has worked extensively in the topics. He is the recipient of the C. Woolf Award for the Excellence in Teaching from the University of Toronto, a Career Scientist Award from the Ontario Ministry of Health, the Young Investigators Award from the Canadian Infectious Disease Society, and Bailey Ashford Medal from the American Society for Tropical Medicine, for distinguished work in tropical medicine. Dr Kain was profiled by TIME magazine as one of “Canada’s Best In Medicine”. He also received the: University of Toronto, Department of Medicine Research Award (2010); Fred Barrett Lectureship, University of Tennessee; Distinguished Global; Health Service Award, University of California (2006); The Wong Lectureship In Medicine, MacMaster (2006), 2005 Forbes Lectureship, University of Melbourne (2005). He has served as a consultant to many organizations including the Gates Foundation, WHO, Red Cross, and the CDC.

Dr. Kain’s research focuses translational research to characterize major global infectious disease threats, particularly as they pertain to women and children. Dr Kain’s efforts are also focused on global equity, knowledge sharing and education, including the training of research scientists in the developing world, enabling and empowering them to address their own problems in a sustainable fashion.


Stephen Lye, PhD

PROJECT

Stephen Lye, PhD, of the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto, and his team will initiate a pilot study that will use a systems biology analysis of genomic, proteomic and plasma markers to identify novel pathways and biomarkers to preterm birth, as well as define the risk of preterm birth in pregnant women. Previous efforts to identify pathways or biomarkers associated with preterm birth have focused on single methodological approaches. With new capabilities in computational analyses, it is now possible to integrate information from multiple analytic techniques – collectively known as systems biology – to derive informative pathways and potential diagnostic biomarkers. 

BIO

Professor Stephen Lye, Ph.D., is Vice-Chair, Research and Professor of Obstetrics & Gynecology at the University of Toronto and Associate Director of the Samuel Lunenfeld Research Institute of Mount Sinai Hospital. Dr. Lye’s research is in the area of women’s and infants’ health, where he has pioneered investigations into the mechanisms underlying preterm birth. His research has integrated discovery, clinical and translational studies including the commercialization of discoveries in partnership with industry. Dr. Lye has documented the molecular changes that occur in the myometrium that contribute to the initiation of labor. Most recently he has identified important contributions from the maternal peripheral immune cells in this process. He has published over 190 research papers on pregnancy and maternal-child health and holds a Canada Research Chair in Improved Health and Function.

Dr. Lye is also the inaugural Executive Director of the Fraser Mustard Institute for Human Development (FMIHD), University of Toronto. The FMIHD brings together faculty from across the University of Toronto and its affiliated research hospitals to focus on the importance of the first 2000 days of life in establishing trajectories that impact a child’s life-long health, learning and social functioning. Dr. Lye has also established international research consortia focused on identifying interactions between an individual’s genetic make-up and their environment during the first 2000 days of life that underlie obesity and cardio-metabolic disorders. Dr. Lye has received numerous awards including the President’s Scientific Achievement Award from the SGI. He was recently appointed a Fellow of the Canadian Academy of Health Sciences.


Sam Mesiano, PhD

PROJECT

Dr. Sam Mesiano from Case Western Reserve University School of Medicine and his team will investigate the body’s receptors for progestin-based therapies in pregnancy to identify ways to enhance anti-inflammatory processes in all pregnant women and prevent preterm birth. The long-term goal of this project is to develop an inexpensive oral therapy that will reduce the prevalence of preterm birth worldwide.

Press release: Grant to Fund Efforts to Reduce Prevalence of Preterm Birth
THINK Magazine profile: Timing Labor - Developing Medications to Extend Pregnancy and Save Babies' Lives
 


BIO

Sam Mesiano, PhD is an Associate Professor in the Department of Reproductive Biology, Case Western Reserve University and serves as Co-Director of the Research Division in the Department of Obstetrics and Gynecology, University Hospitals, and Director of the Umbilical Cord Blood Collection Program, MacDonald Women’s Hospital. He is a graduate of Monash University, Melbourne Australia, where he received a PhD in Physiology specializing in the hormonal control of fetal growth. His research as a Postdoctoral Fellow and adjunct faculty member in the Center for Reproductive Sciences at the University of California, San Francisco explored the functional biology of the human fetal adrenal cortex.

As a Senior Lecturer and Principal Investigator in the Mothers and Babies Research Centre at the University of Newcastle, Australia, Dr. Mesiano examined the role of steroid hormones in the control of human pregnancy and parturition. At Case Western Reserve University he continues to perform ground breaking research into the molecular endocrinology of human pregnancy and parturition, with specific emphasis on understanding the mechanism by which progesterone promotes pregnancy and how those actions can be exploited to prevent preterm birth.


David Olson, PhD, FRCOG

PROJECT

Dr. David Olson from the University of Alberta will be working to better understand how infections can cause preterm birth. Using animal models and in later studies of women in low-income countries, he and his team will investigate multiple mediators of inflammation in the uterus early in pregnancy, as well as test new diagnostics and therapeutics that can identify women at risk, modulate the inflammatory response, and prolong pregnancy. His research was selected as one of the Top 10 Discoveries of the Year for 2015 by Quebec Science magazine.

Press release: Preventing premature births worldwide
 

BIO

David M. Olson, PhD, FRCOG is Professor of Obstetrics and Gynecology, Pediatrics and Physiology at the University of Alberta. His career and research program have been dedicated to improving maternal-child health. Educated at Augustana College (Sioux Falls, SD), the University of Minnesota, St. Louis University, and the University of Western Ontario, he served as the founding director or co-director of the University of Alberta Perinatal Research Centre, the CIHR Group in Perinatal Health and Disease, the CIHR Strategic Training Initiative in Maternal-Fetal-Newborn Health Research, and the AIHS Interdisciplinary Preterm Birth and Healthy Outcomes Team. He has raised more than $30 M for research.

He is a founding board member of the Child Health Research Institute (London, Ontario), The Alberta Centre for Child, Family and Community Research and has served several national and international societies in elected office. He has organized the annual Western Perinatal Research Meeting for twenty-one years in Banff. His laboratory has published more than 140 papers primarily on the interactions of inflammatory mediators, steroids and prostaglandins on the activation of the uterus and initiation of term and preterm birth. Recently he has filed patents and started four companies to better translate laboratory discoveries to improve perinatal health.


Round 2: Research Sites

Anisur Rahman, PhD

PROJECT

In Bangladesh, Anisur Rahman, PhD, head of the Matlab Health Research Centre at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), will work with his team to enroll 4,700 pregnant women over 3 years.

“We have a very good system for identifying pregnancy, as well as for staying in contact with mothers and babies after pregnancy to collect follow-up data and samples,” Rahman said. “Our center has the potential to contribute a lot to global research, because preterm birth is shared by both developed and developing countries.”


Jeffrey Stringer, MD

PROJECT

In Lusaka, Zambia, Jeffrey Stringer, MD, an obstetrician and director of the University of North Carolina Global Women’s Health group, will oversee a team of Zambian and U.S. researchers in enrolling 2,000 high-risk pregnant women over a 3 year period.

Dr. Stringer, who lived and worked in Zambia for more than a decade, has seen firsthand how the prevalence of infant death impacts families. “There is nothing more devastating than the loss of a child. Whether you live in North America or Zambia, this is a universal truth.” Stringer said. “We will set up a carefully monitored cohort of women and their newborns so we can evaluate the causes of prematurity and figure out ways to prevent it.”

BIO

Dr. Jeffrey Stringer received his medical degree from Columbia University and completed an OB-GYN residency at the University of Alabama-Birmingham in 1999. Between 2001 and 2012 he lived full time in Zambia. There he established and led the Centre for Infectious Disease Research in Zambia (CIDRZ), a 600-person non-profit company with an annual budget exceeding $35 million. The CIDRZ clinical research infrastructure at CIDRZ has dedicated units for research operations and data management/analysis. CIDRZ began supporting services to prevent mother-to-child HIV transmission in 2001. Since that time, it has reached over 1,400,000 women with services to protect their infants from HIV infection. In 2003, CIDRZ launched a family-centered AIDS treatment program that has now treated more than 250,000 adults and children with antiretroviral drugs. The organization also works in cervical cancer screening (more than 100,000 women served) and in safe obstetrics. CIDRZ has completed 62 studies and enrolled over 14,000 patients into prospective protocols. Their bibliography has more than 190 entries, including publications in JAMA, Lancet, BMJ, NEJM, and PLoS Medicine.

Dr. Stringer has expertise in the planning, conduct, and analysis of clinical trials and observational cohorts, and has conducted and published several such studies. His experience working in Africa has made him increasingly interested in the area of implementation research, having seen up-close the human cost of health systems failing to implement interventions that are known to work. Understanding this “implementation gap” has become an increasingly important aspect of the group’s work, and they are now considered accomplished experts in the field of implementation research. 


Round 3: Systems Biology Projects

Gregory A. Buck, PhD, and Jennifer M. Fettweis, PhD

PROJECT

Gregory Buck, PhD, and Jennifer Fettweis, PhD, and their team at Virginia Commonwealth University are performing proteomic and metabolomic analysis on biospecimens from pregnant women. They will research changes in the microbiome throughout pregnancy and determine how they contribute to preterm birth. This will help them identify predictive biomarkers that will allow development of early interventions to prevent preterm birth and other adverse pregnancy outcomes. 

BIOS

Dr. Gregory A. Buck is the Director of the Center for the Study of Biological Complexity and Professor of Microbiology and Immunology at VCU. After graduating from the University of Wisconsin with a degree in Genetics, he obtained an MS and Ph.D. in Microbiology and Immunology from the University of Washington. In the late 1990’s, Dr. Buck spearheaded the Cryptosporidium Genome Projects, which led to the publication of some of the first protozoan genomes (C. hominis and C. parvum), and other bacterial genomes (e.g., Streptococcus sanguinis). Dr. Buck subsequently led the NIH-funded Kinetoplastid Genome Sequencing Project, an effort to sequence the genomes up to 25 species of human health relevant kinetoplastid protozoa, a project that is ongoing at the Washington University Genome Center. His work refocused on high throughput genomics with the advent of Next Generation Sequencing and was funded by the NSF Assembling the Tree of Life Project to apply NGS to characterize the genomes of members of the Phylum Euglenozoa. Simultaneously, Dr. Buck’s team launched into microbiome research in Phase I of NIH’s Human Microbiome Project as he led the Vaginal Human Microbiome Project: Disease, Genetics and the Environment (VaHMP). 

Dr. Buck’s team was subsequently selected to extend this research into an exploration of the contributions of the vaginal and related microbiomes to health and disease during pregnancy in the Multi Omic Microbiome Study: Pregnancy Initiative (MOMS PI) in Phase II of NIH’s Human Microbiome. Between the latter two studies, over 150,000 samples will be collected (>40,000 from 6,000 women participants in VaHMP; >100,000 from 2,000 pregnant women in MOMS PI) and analyzed with multiple omic technologies (16S rRNA taxonomic surveys, whole metagenome/metatranscriptome sequencing, whole genome (bacterial/human) sequencing, immunoproteomic and metabolomic analysis). Thus, Dr. Buck’s research focuses on the ‘omics’ of the microbiome-host interaction. 

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Jennifer M. Fettweis, Ph.D. is the Project Director for the Vaginal Microbiome Consortium at Virginia Commonwealth University and Assistant Professor in the Center for the Study of Biological Complexity (CSBC) and the Department of Obstetrics and Gynecology. She has been a Fellow in the CSBC since 2009. Dr. Fettweis was awarded a BA in Mathematics and Economics from the University of Virginia and a PhD in Microbiology and Immunology from Virginia Commonwealth University. She coordinates two projects funded through the NIH’s Human Microbiome Project: the Vaginal Human Microbiome Project and the Multi-‘Omic Microbiome Study-Pregnancy Initiative. She founded the Research Alliance for Microbiome Science (RAMS) Registry at VCU, which houses a participant registry and a biorepository, to promote collaboration among researchers and sharing and reuse of data and samples. Her primary research interests include host-microbiome interactions in women’s health with a focus on understanding how these interactions impact women’s health, pregnancy outcomes and vertical transmission of the microbiome from mother to infant.

She has significant experience in genome biology, bioinformatics, next-generation sequencing, host-microbiome studies, metagenomics, ‘omics technologies, translational research and innate immunity. Dr. Fettweis she has almost a decade of experience planning, building and overseeing large multi-institutional research projects, including the integration and analysis of large complex ‘omics datasets. Dr. Fettweis has developed methodologies and approaches for providing species-level and strain-level resolution of vaginal microbiome data. These approaches have permitted genomic characterization of several vaginal bacterial species of interest thought to adversely affect reproductive health.


Elaine Holmes, PhD

PROJECT

Elaine Holmes, PhD, and her team at Imperial College London are researching the microbiome and metabolome of pregnant women who deliver either at term or preterm, and evaluate connections between biological processes of pregnancy by analyzing data to predict women at risk for preterm birth.

 

Robert C. Murphy, PhD

PROJECT

Robert C. Murphy, PhD, and his team at University of Colorado Denver are investigating lipid and hormone biochemistry of pregnant women who deliver either at term or preterm. They will use mass spectrometry – a way of measuring the characteristics of individual molecules by turning them into ions – to analyze a broad spectrum of lipids in biospecimens from pregnant women to identify biomarkers and determine pregnant women at risk for preterm birth.

BIO

Robert C. Murphy, Professor, Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, graduated from the Massachusetts Institute of Technology in 1970 with a Ph.D. in chemistry and is currently a University Distinguished Professor at the University of Colorado. He has worked in the area of mass spectrometry and eicosanoid biochemistry for approximately 40 years with much of his research activities centered around the use of mass spectrometry to studies of arachidonic acid biochemistry and formation of the biologically active leukotriene mediators. His interests also include the structural characterization of bioactive lipid products derived from the reaction of reactive oxygen species with cellular lipids. 

He has authored over 500 peer-reviewed papers in scientific journals and several books concerning the mass spectrometry of lipids. He served as President of the American Society for Mass Spectrometry and is on the editorial boards of numerous scientific journals in biochemistry and mass spectrometry. He has received several awards including the Dean’s Mentoring Award, the Faculty Excellence in Teaching Award, an NIH Merit Award, and the Eicosanoid Research Foundation Outstanding Achievement Award. His present research program focuses on details of transcellular biosynthesis of leukotrienes, the formation of biologically active lipid products from exposure of ozone to the lung, the advancement of biochemistry in the area of lipidomics analysis, and the imaging of complex lipids in tissues by mass spectrometry.

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