Helen N. Jones, Ph.D.

Associate Professor

Jones, Helen
Helen Jones, PhD

Phone: (352) 846-1503
Office: MSB M543
Email: jonesh@ufl.edu
PubMed Listing

Education and Training/Previous Appointments

  • 2019-20: Associate Professor (TT): Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH
  • 2018-20: Head of Research: Center for Fetal and Placental Research, Divisions of General Pediatric and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
  • 2013-19: Assistant Professor (TT): Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH
  • 2010-13: Assistant Professor (Research): Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH
  • 2009-10: Research Associate: Center for Molecular Fetal Therapy,  Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
  • 2006-09: Postdoctoral Trainee: University of Cincinnati, Cincinnati, OH (Obstetrics and Gynecology)
  • 2005: Ph.D.: University of Aberdeen, Aberdeen, U.K. (Physiology)
  • 2000: B.Sc.: University of St. Andrews, St. Andrews, U.K. (Biochemistry)

Research Interests

Malformations of the maternal-fetal interface underlie many pregnancy pathologies and may also contribute to congenital malformations, all of which have acute and chronic sequelae for both mother and baby. My current and future research investigates the development and function and potential for treatment of this interface in 3 highly significant conditions; Fetal Growth Restriction, Congenital Heart defects and Placenta Accreta spectrum.

Fetal Growth Restriction:

In 2016, 1 in 12 babies (8.2% of live births) was low birthweight in the United States (Peristats, March of Dimes). It is thought that there are at least twice these numbers in developing countries. Approximately 75% of these cases of Intra-Uterine Growth Restriction (IUGR) are due to Placental Insufficiency (PI). Babies that are born prematurely and/or low birthweight face sequelae of immediate issues including the increased risk for cesarean delivery, hypoxia, hypoglycemia, polycythemia, motor and neurological disabilities and higher levels of infant mortality. Additionally low birthweight is associated with the increased risk of developing metabolic syndrome (obesity, diabetes and cardiovascular disease) in adulthood, a phenomenon known as Fetal Programming. In 2008, 34% of the adult population in the U.S.A were obese, 8% had diabetes and cardiovascular disease accounted for 1 in every 3 deaths (Roger et al. 2012), although it is not known what contribution IUGR makes to the numbers of cases of these diseases any reduction in these figures is desirable. The alleviation of pregnancy related pathologies will not only reduce both neonatal and maternal morbidities and mortalities but may also lead to a therapy before birth that would lower the risk of adult obesity, diabetes and CVD and reduce the cost burden of these diseases on healthcare services in the future. There is currently no treatment for placental insufficiency or impaired placentation. In my initial research I have focused on the treatment of IUGR due to placental insufficiency using placental gene transfer of IGF-1. Alterations in the maternal, fetal and placental IGF axis are associated with IUGR in human pregnancy but how this affects placental development and function or fetal growth still needs investigation. This contribution is significant because it has the potential to move the field forward in our understanding of normal placental development and metabolism, further our knowledge of IGF-1 function in the placenta and lead to the development of the first effective treatment for placental insufficiency and fetal growth restriction. Studying the placenta through systems biology integrates molecular biology, cellular and whole organ physiology allowing understanding of its role in pathological pregnancies While gene transfer has inherent potential risks of insertional mutagenesis and germline gene transfer, the disposable nature of the placenta mitigates many of these risks identifying the placenta as a potential target not only for placental therapies but also to aid in future development of fetal gene and drug therapy for other in utero complications or infections. My vision for my future research is to develop a treatment for these pathologies and in doing so increase our knowledge of their underlying mechanisms and normal placental function and metabolism, and links to development of adult metabolic diseases a field of research that desperately needs more understanding. The use of placental gene therapy is highly innovative, challenging current paradigms for the management of Intra-Uterine Growth Restriction and holds the promise of significantly advancing the fields of gene therapy, placental biology and the use of non-destructive nanoparticle delivery systems. It not only offers innovative treatment strategies, but also provides new insights into the mechanisms underlying placental pathologies. It also provides an experimental means to test Barker’s fetal programming hypothesis and to prevent adult metabolic disorders before the patient is even born.

Congenital Heart Defects:

Congenital heart disease (CHD) is the most common birth defect, affecting ~1% of all live births. Population studies have recently demonstrated that pregnancies complicated by CHD also carry a higher risk of developing pathologies associated with an abnormal placenta including growth disturbances, preeclampsia, preterm birth, and stillbirth   Placental abnormalities in cases of congenital heart disease are understudied. This project aims to identify potential mechanisms and targets for clinical intervention in the placenta from fetuses with congenital heart disease. Comparison of placentas from a CHD cohort with age-matched controls identified abnormal morphology, suggesting immature structure and villous vascular abnormalities. While vascular abnormalities are common amongst subtypes of CHD, impaired fetal growth appears associated with impaired trophoblast development. Utilizing murine models of Hand1 disruption we are elucidating the development in the placenta in early pregnancy that may contribute to both the etiology of CHDs as well as placental remodeling in later pregnancy that may impact fetal development and growth throughout gestation. Nutrient and oxygen supply to the developing fetus is dependent on the proper formation and function of the placenta. Genes commonly associated with the risk of CHD are also vital to the development and remodeling different cells of the placenta throughout pregnancy, as such, a target for improving nutrient and oxygen supply and in turn fetal development and growth in this population may exist. Furthermore, disrupted placental development and function may be measurable via sampling of the maternal circulation earlier in pregnancy. Placental output, now known to be far greater than the classical placental hormones, includes extracellular vesicles, cell-free nucleic acids and many other secreted proteins, which are accessible, quantifiable and may enable identification of disrupted development well before seen on mid-pregnancy ultrasound. Identifying signatures of disrupted placental development in mid-pregnancy in mothers carrying a fetus with CHD will be investigated and assessed alongside maternal nutritional information using extracellular vesicles isolated from maternal blood.

Placenta Accreta Spectrum:

Placenta accreta syndrome (PAS) is an umbrella term used to describe the clinical condition of invasive placentation with failure to separate from the uterine wall at delivery and can result in massive maternal hemorrhage. The incidence of placenta accreta has increased significantly over the last decades from 1 in ~800 to the current estimate of 1 in ~350 deliveries. While in part this increase may be linked to the increase in cesarean delivery rate, immunological and/or genetic factors are thought to play an important role as well. Despite the vital roles of uNK cells in the establishment of the maternal-fetal interface, the molecular mechanisms underlying their function and interaction with the invading trophoblast and the cellular milieu of the decidua basalis during gestation remain poorly understood. Understanding the underlying mechanisms of regulating trophoblast invasion is critical to developing mechanisms for diagnosis and treatment of Placental Accreta Spectrum. Following a screening protocol for NK phenotypes with ENU mutagenesis, my collaborators identified frequent dystocia when attempting to expand their colony. We went on to demonstrate that the SNP present in the GAB3 protein in uterine NK cells was detrimental for successful pregnancy and characterized the maternal-fetal interface throughout gestation. Throughout pregnancy abnormal trophoblast invasion occurred via both endovascular and interstitial routes, with abnormal spiral artery remodeling in early pregnancy and trophoblast reaching the uterine wall by 18.5 days. Current studies involve both further investigation into the NK-trophoblast signaling throughout the pregnancy and the impact of interstitial giant cell invasion on the mouse decidua.

Importantly, in humans, the risk of carrying this SNP or one of 27 in the same region, which are proposed to be as deleterious to proper GAB3 function, is 1:900, furthermore it is clear from the Exac database that loss of GAB3 is incompatible with life. The role of GAB3 in human uNK cells remains unknown and currently I have built global collaborations to access sufficient patient sample size to assess GAB3 in PAS pregnancies. Through a combination of studies into isolated primary uNK-EVT interaction in the presence of disrupted GAB3, the transcriptome of EVTs in PAS samples in response to abnormal uNK signaling and genotyping of women diagnosed with PAS I hope to identify a potential causative agent and mechanism.

Teaching (Including Courses)

  • Reproductive and Perinatal Biology Seminar (ANS 5935)
  • Physiology of Reproduction (ANS 6751)
  • Seminar in Physiology (GMS 6495)
  • Human Physiology for Physician Assistants (PAS 5025)

Awards and Honors

  • 2018: CCHMC Young Professional of the Year Nominee
  • 2014: Gabor Than Award Nominee
  • 2013: Perinatal Research Society Early Career Speaker
  • 2008: Perinatal Research Society New Investigator Award
  • 3007: NICHD Aspen Perinatal Symposium Travel Award
  • 2006-07: International Federation of Placenta Associations NIH New Investigator Awards
  • 2004: Society for Reproduction and Fertility travel grant
  • 2004: Physiological Society Affiliate member travel grant
  • 2003-05: International Federation of Placenta Associations Y W (Charlie) Loke Young Investigator Awards

Publications

PubMed Listing

  • Jones, H. N., Olbrych, S. K., Smith, K. L., Cnota, J. F., Habli, M., Ramos-Gonzales, O., Owens, K. J., Hinton, A. C., Polzin, W. J., Muglia, L. J., & Hinton, R. B.  (2015). Hypoplastic left heart syndrome is associated with structural and vascular placental abnormalities and leptin dysregulation. Placenta, 36(10), 1078-86. doi: 10.1016/j.placenta.2015.08.003. Epub 2015 Aug 7. (PMID: 26278057; PMCID: PMC4609616)
  • Abd Ellah, N., Taylor, L., Troja, W., Owens, K., Ayres, N., Pauletti, G., & Jones, H. (2015). Development of Non-Viral, Trophoblast-Specific Gene Delivery for Placental Therapy. PLoS One, 10(10), e0140879. doi: 10.1371/journal.pone.0140879. (PMID: 26473479; PMCID: PMC4608830)
  • Pavličev, M., Wagner, G. P., Chavan, A. R., Owens, K., Maziarz, J., Dunn-Fletcher, C., Kallapur, S. G., Muglia, L., & Jones, H. (2017). Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface. Genome Res, 27(3), 349-361. doi: 10.1101/gr.207597.116. Epub 2017 Feb 7. (PMID: 28174237; PMCID: PMC5340963)
  • Rebholz, S. L., Melchior, J. T., Davidson, W. S., Jones, H. N., Welge, J. A., Prentice, A. M., Moore, S. E., & Woollett, L. A. (2018). Studies in genetically modified mice implicate maternal HDL as a mediator of fetal growth. FASEB J, 32(2), 717-727. doi: 10.1096/fj.201700528R. Epub 2018 Jan 4. (PMID: 28982731; PMCID: PMC6266630)
  • Courtney, J. A., Cnota, J. F., & Jones, H. N. (2018). The Role of Abnormal Placentation in Congenital Heart Disease; Cause, Correlate, or Consequence? Front Physiol., 9, 1045. doi: 10.3389/fphys.2018.01045 (PMID: 30131711; PMCID: PMC6091057)
  • Sliz, A., Sullivan, K. C., Lampe, K., Godarova, A., Plas, D. R., Janssen, E., Jones, H., Herr, A., & Hoebe, K. (2019). The GRB2-associated binding protein 3 is required for IL-2- and IL-15- induced NK cell expansion and successful pregnancy. Science Immunology.
  • Brockway, H. M., Kallapur, S. G., Buhimschi, I. A., Buhimschi, C. S., Ackerman, W. E., Muglia, L. J., & Jones, H.N. (2019). Unique transcriptomic landscapes identified in idiopathic spontaneous and infection related preterm births compared to normal term births. PLoS One, 14(11), e0225062. doi: 10.1371/journal.pone.0225062. (PMID: 31703110; PMCID: PMC6839872)
  • Wilson, R. L., Owens, K., Sumser, E. K., Fry, M. V., Stephens, K. K., Chuecos, M., Carrillo, M., Schlabritz-Loutsevitch, N., & Jones, H. N. (2020). Nanoparticle mediated increased insulin-like growth factor 1 expression enhances human placenta syncytium function. Placenta, 93, 1-7. doi: 10.1016/j.placenta.2020.02.006. Epub 2020 Feb 12. (PMID: 32090963; PMCID: PMC7167609)
  • Courtney, J., Troja, W., Owens, K. J., Brockway, H. M., Hinton, A. C., Hinton, R. B., Cnota, J. F., & Jones, H. N. (2020). Abnormalities of placental development and function are associated with the different fetal growth patterns of hypoplastic left heart syndrome and transposition of the great arteries. Placenta, 101, 57-65. doi: 10.1016/j.placenta.2020.09.007. Epub 2020 Sep 6. (PMID: 32927345)
  • Courtney, J. A., Cnota, J., & Jones, H. Impaired labyrinth formation prevents the establishment of the maternal-fetal interface in conditional Hand1-deficient mice.  bioRxiv 2020.09.02.280354; doi: https://doi.org/10.1101/2020.09.02.280354