Saturday, September 28

Pregnancy is a window to assess cardiovascular health and can impact later-life maternal and offspring cardiovascular health, thus impacting future generations. Dr. Davidge’s research is focused on understanding mechanisms for vascular complications of pregnancy (e.g. preeclampsia, maternal aging) and developmental origins of cardiovascular disease. The impact of this research is to ultimately develop novel therapeutic strategies to improve pregnancy outcomes and minimize the impact of pregnancy complications on both maternal and offspring cardiovascular health.

Title: Understanding Disparities in Preterm Birth.  “New insights into the immunologic and signaling processes that determine gestational length in pregnancy have revealed important complexity in the interactions (ancestral and current) between genetic and environmental forces.  A better understanding of these relationships could guide research efforts which, in turn, could lead to a reduction in disparities in preterm birth by introducing effective clinical and public health interventions.” 

Title: Maternal obesity and gestational diabetes; short and long term effects on the offspring.  Maternal obesity and diabetes have independent effects on fetal growth.  Long-term, maternal gestational diabetes is associated primarily with childhood glucose metabolism, while maternal obesity is primarily associated with childhood adiposity.

11:15 – 11:35 am

Hypoxic ischemic (HI) insults during pregnancy and birth can result in long term neurodevelopmental disorders, such as cerebral palsy. We have previously shown that human umbilical cord blood (hUCB) cells are effective at reducing neuroinflammation and improving brain injury in the short-term. In this current study we aimed to examine the long-term behavioural outcomes and neuropathology, specifically the beneficial effect of repeated doses of hUCB and different administration routes. Using a pre-clinical rodent model of HI, we showed that treatment with repeated doses of hUCB cells is more effective than a single dose for reducing long-term tissue damage and restoring behavioural deficits following perinatal brain injury. We hope this research will lead to improved clinical trial designs for the treatment of perinatal brain injury.

Neonates are uniquely susceptible to infection, with neonatal sepsis accounting for 1.4 million deaths annually worldwide. Unlike adults, in whom infection mobilizes a large pool of neutrophils from the bone marrow that are rapidly replenished by upstream progenitors, neonates often become neutropenic upon infection, resulting significant morbidity and mortality.  This presentation will focus on the mechanisms underpinning this divergence in activation of emergency myelopoiesis pathways at the level of hematopoietic stem cells, which is fundamental for understanding the differences in mortality and morbidity resulting from inflammation and infection at these developmentally disparate times of life.

Between 15-30% of placentae are diagnosed with villitis of unknown etiology, which is characterized by the infiltration of CD8+ maternal immune cells and can lead to growth restriction and fetal demise.  Studies are under way to better define the function of these T cells and understand the mechanisms at the fetal-maternal interface that lead to this rejection type response.

Title: Towards effective therapies for neonatal pulmonary hypertension: A bench to bedside Journey. Treatments for infants with pulmonary hypertension associated with chronic cardiopulmonary disorders remain inadequate.  The presentation will chronicle Dr. Fike’s “bench –to – bedside“ journey to develop safe, practical, and effective therapies for these therapies for these infants.

Title: Immunoperinatology: Placental determinants of neonatal health and disease

The “Valley of Death” metaphorically describes the gap between basic research discoveries and their applications in clinical practice. Over the past ten years, funding agencies have tried making the Valley of Death more navigable for academic researchers so that innovations can be more rapidly transitioned into useful interventions. This talk will examine three important problems in perinatal research: preeclampsia, preterm birth, and optimization of perinatal outcomes. Despite the overwhelming need to address these issues, diagnostic and therapeutic innovation has lagged behind other fields such as cancer, HIV, or cardiovascular research. Drawing from personal experiences, the presentation will review critical elements of successful translational science that are seldom discussed, including intellectual property, technology transfer, and partnerships for scale and sustainability.

Given the established role of oxidative stress in the pathobiology of perinatal diseases, the potential efficacy of redox-based therapeutic has been supported by numerous preclinical studies.  Unfortunately, these approaches have failed to translate into meaningful clinical therapies.  Using examples from his ongoing research, Dr. Tipple will demonstrate how sufficient appreciation of the complexities of redox biology, when coupled with realistic modeling of clinical scenarios, can bridge the bench to bedside gap in perinatal redox biology.

Title:  Mediators of impaired fetoplacental angiogenesis in severe fetal growth restriction.  Abnormal umbilical artery Doppler velocimetry in growth-restricted fetuses is an ominous finding that substantially increases risk for adverse perinatal and long-term outcomes. Impaired placental angiogenesis resulting in abnormally thin, unbranched villous vessels is a common pathologic finding in the pregnancies  and is a structural cause of aberrantly elevated fetoplacental vascular resistance.  In a model of human fetoplancetalendothelial cells, we have found various mechanisms that underlie deficient angiogenesis in severe fetal growth restriction.