Sarah K. England

Last updated
Sarah K. England
Born
St. Paul, Minnesota, U.S.
Alma mater Carleton College
Medical College of Wisconsin
Known forStudying effects of ion channel physiology in uterine smooth muscle on preterm birth
AwardsRobert Wood Johnson Health Policy Fellow, March of the Dimes Prematurity Research Initiative Grantee
Scientific career
FieldsObstetrics and gynaecology, physiology
Institutions Washington University in St. Louis
University of Iowa

Sarah K. England is a physiologist and biophysicist and the Alan A. and Edith L. Wolff Professor of Obstetrics and Gynaecology at Washington University School of Medicine. England conducts research on cation channels in uterine smooth muscle to understand the biological correlates of preterm birth and is the Associate Program Director of the Prematurity Research Center at Washington University as well as the Vice Chair of Research for the Center for Reproductive Health Sciences. In 2005, England was selected as a Robert Wood Johnson Foundation Health Policy Fellow in the Office of Senator Hillary Clinton where she used her scientific expertise in obstetrics and gynaecology to guide policy changes.

Contents

Early life and education

England was born in St. Paul, Minnesota. [1] Her family moved to the Highland Park neighbourhood in 1969 after the Fair Housing Act was passed so that England and her four brothers could obtain a better quality education. [1] England's father was a physician and her mother worked in real estate and they made sure that education was a priority in the family. [1] England had always loved science, and decided to pursue a career in academia instead of medicine. [1]

In 1984, England pursued her undergraduate degree at Carleton College, a small private liberal arts college in Northfield, Minnesota. [2] She majored in biology and conducted research under the mentorship of John W. Osborn at the University of Minnesota in St. Paul studying the sympathetic nervous system response after barodenervation. [3] This led to her first publication in the American Journal of Physiology in 1990. [3] England completed her Bachelor of Arts in 1988, and then in 1989, she pursued her graduate training in physiology at the Medical College of Wisconsin. [1] She studied under the mentorship of Nancy J. Rusch exploring the role of cation channels in hypertension. [4] She found that calcium dependent potassium channel function is aberrant in specific patches of arterial muscle in rats in rats with genetic hypertension. [4] The potassium channels had a higher probability of open-state leading to increased potassium permeability and overall dysregulation of membrane excitability and contraction. [4] England completed her graduate studies in 1993. [5]

Following her graduate work, England pursued her postdoctoral work at Vanderbilt University under the mentorship of Michael M. Tamkun in the Department of Molecular Physiology and Biophysics. [5]  She continued to study voltage-gated potassium channel biophysics, exploring the role they play in smooth muscle tone in the vascular system and how their activity is implicated in blood pressure regulation. [5] She published a first author paper in the Proceedings of the National Academia of Sciences in 1995 characterizing the presence and functionality of beta subunits of voltage-gated potassium channels in human heart tissue. [6] Her findings highlighted the possibility that potassium current diversity in the heart is in part due to the function and expression of beta subunits for voltage-gated potassium channels. [6] She also discovered a novel potassium channel beta subunit, cloned from human heart tissue. She found that this beta-subunit she discovered is generated from alternative splicing of a beta-subunit gene which gives rise to two other previously discovered beta-subunits. [6] Her discovery of alternative splicing mechanisms suggests that potassium channel current diversity and heart tissue excitability diversity may be in part due to alternative splicing events. [6] England completed her postdoctoral training in 1997. [7]

Career and research

In 1997, England was appointed to the faculty at the University of Iowa, becoming an assistant professor in the Carver College of Medicine in the Departments of Molecular Physiology and Biophysics. [7] While at U of I, England turned her research focus towards exploring ion channel function in the uterus during pregnancy. [7] England became a Full Professor of Obstetrics and Gynaecology, and well as a full professor in pediatrics. [8] She was also appointed special assistant to the Vice President of Medical Affairs at U of I. [9]

England lead many educational programs to enhance diversity and inclusion in the institute. [10] England became a co-director of the Iowa Biosciences Advantage Program, which is a National Institutes of Health funded program that aims to increase the participation and recruitment of minority students in biomedical graduate degrees. [11] In addition to being a student mentor in the program, England worked hard to improve the program and make it an established and mainstay program at U of I. [11]

From 2005 to 2006, England took a one-year leave from her roles at the University of Iowa to become a Robert Wood Johnson Foundation Health Policy Fellow in the Office of Senator Hillary Rodham Clinton on Capitol Hill. [12] During this time, she helped draft legislations on issues related to her research on preterm birth and pregnancy, efficiently linking her science to policy changes. [1] She also focused much of her fellowship work to policies more generally surrounding maternal child health, women's health, and health disparities. [7]

In 2011, England joined the faculty at the Washington University School of Medicine in St. Louis, Missouri. [1] She became a Professor of Obstetrics and Gynaecology, as well as the Vice Chair of Research for the Center for Reproductive Health Sciences and in 2015, was appointed the Alan A. and Edith L. Wolff Professor of Medicine. [13] Funded by the March of the Dimes, England serves as Associate Program Director and Theme 3 Leader of the Prematurity Research Center at Washington University, working with a team of researchers across the university [7] and across the world to end prematurity. [14]

England is also the Principal Investigator of the England Lab where she explores the physiology of ion channels in smooth muscle as a means to target these mechanisms in muscle diseases. [15] She focuses on both vascular and uterine smooth muscle, with a specific focus on the implications of uterine ion channels in preterm birth. [15] One of her projects explored the localization and activity of BK channels and how they alter myometrial excitability and uterine contractility. [16]

Oxytocin and labor

Another facet of England's research program focuses on the role of oxytocin in uterine contractility and how variations in response to oxytocin might lead to labor dysfunction. [17] Oxytocin is a frequently used drug is obstetrics and gynaecology, and England was interested in exploring the safety of this frequent practice by characterizing women who require high doses of oxytocin for adequate cervical dilation during labor. [18] They found that factors associated with higher necessary oxytocin dose were correlated with poor labor progress. [18] Since this study highlighted the need to look at genetic variation in women requiring high oxytocin levels during labor, England and her team conducted a large scale genetic analysis finding that women requiring high doses of oxytocin had enriched levels of a novel oxytocin receptor variant. [19] The variants of oxytocin receptor that were predicted to interfere with oxytocin binding were enriched in women that required higher doses of oxytocin during pregnancy. [19] In a following study, England and her team explored how oxytocin increases the excitability of smooth muscle in the uterus and she found that it inhibits the SLO2.1 potassium channels to modulate electrical activity. [20]

Chronodisruption and preterm birth

England has also began an investigation of the role of chronobiology on preterm birth, through the Prematurity Research Center at WUSTL. [21] The goal of this program is explore how disruptions to circadian rhythm affect the risk of preterm birth. [21] England and Erik D. Herzog, a colleague at Washington University who studies chronobiology, explored how daily rhythms change in pregnancy. [22] They found that the time of onset and the amount of activity changes throughout pregnancy in both mice and women. [22] They are now exploring whether polymorphisms in genes that affect circadian rhythms lead to increased susceptibility of preterm births. [23]

Awards and honors

Select publications

Related Research Articles

<span class="mw-page-title-main">Misoprostol</span> Medication to induce abortion and treat ulcers

Misoprostol is a synthetic prostaglandin medication used to prevent and treat stomach and duodenal ulcers, induce labor, cause an abortion, and treat postpartum bleeding due to poor contraction of the uterus. It is taken by mouth when used to prevent gastric ulcers in people taking nonsteroidal anti-inflammatory drugs (NSAID). For abortions it is used by itself or in conjunction with mifepristone or methotrexate. By itself, effectiveness for abortion is between 66% and 90%. For labor induction or abortion, it is taken by mouth, dissolved in the mouth, or placed in the vagina. For postpartum bleeding it may also be used rectally.

Uterine contractions are muscle contractions of the uterine smooth muscle that occur during the menstrual cycle and labour. Uterine contractions occur throughout the menstrual cycle in the non-pregnant state and throughout gestation.

<span class="mw-page-title-main">Atosiban</span> Chemical compound

Atosiban, sold under the brand name Tractocile among others, is an inhibitor of the hormones oxytocin and vasopressin. It is used as an intravenous medication as a labour repressant (tocolytic) to halt premature labor. It was developed by Ferring Pharmaceuticals in Sweden and first reported in the literature in 1985. Originally marketed by Ferring Pharmaceuticals, it is licensed in proprietary and generic forms for the delay of imminent preterm birth in pregnant adult women.

Tocolytics are medications used to suppress premature labor. Preterm birth accounts for 70% of neonatal deaths. Therefore, tocolytic therapy is provided when delivery would result in premature birth, postponing delivery long enough for the administration of glucocorticoids, which accelerate fetal lung maturity but may require one to two days to take effect.

Bloody show or show is the passage of a small amount of blood or blood-tinged mucus through the vagina near the end of pregnancy. It is caused by thinning and dilation of the cervix, leading to detachment of the cervical mucus plug that seals the cervix during pregnancy and tearing of small cervical blood vessels, and is one of the signs that labor may be imminent. The bloody show may be expelled from the vagina in pieces or altogether and often appears as a jelly-like piece of mucus stained with blood. Although the bloody show may be alarming at first, it is not a concern of patient health after 37 weeks gestation.

<span class="mw-page-title-main">Glibenclamide</span> Chemical compound

Glibenclamide, also known as glyburide, is an antidiabetic medication used to treat type 2 diabetes. It is recommended that it be taken together with diet and exercise. It may be used with other antidiabetic medication. It is not recommended for use by itself in type 1 diabetes. It is taken by mouth.

Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically related to calcium gated channels. They were first discovered in 1958 by Gardos who saw that calcium levels inside of a cell could affect the permeability of potassium through that cell membrane. Then in 1970, Meech was the first to observe that intracellular calcium could trigger potassium currents. In humans they are divided into three subtypes: large conductance or BK channels, which have very high conductance which range from 100 to 300 pS, intermediate conductance or IK channels, with intermediate conductance ranging from 25 to 100 pS, and small conductance or SK channels with small conductances from 2-25 pS.

An ATP-sensitive potassium channel is a type of potassium channel that is gated by intracellular nucleotides, ATP and ADP. ATP-sensitive potassium channels are composed of Kir6.x-type subunits and sulfonylurea receptor (SUR) subunits, along with additional components. KATP channels are found in the plasma membrane; however some may also be found on subcellular membranes. These latter classes of KATP channels can be classified as being either sarcolemmal ("sarcKATP"), mitochondrial ("mitoKATP"), or nuclear ("nucKATP").

In molecular biology, the sulfonylurea receptors (SUR) are membrane proteins which are the molecular targets of the sulfonylurea class of antidiabetic drugs whose mechanism of action is to promote insulin release from pancreatic beta cells. More specifically, SUR proteins are subunits of the inward-rectifier potassium ion channels Kir6.x. The association of four Kir6.x and four SUR subunits form an ion conducting channel commonly referred to as the KATP channel.

<span class="mw-page-title-main">Prostaglandin F2alpha</span> Chemical compound

Prostaglandin F2α, pharmaceutically termed carboprost is a naturally occurring prostaglandin used in medicine to induce labor and as an abortifacient. Prostaglandins are lipids throughout the entire body that have a hormone-like function. In pregnancy, PGF2 is medically used to sustain contracture and provoke myometrial ischemia to accelerate labor and prevent significant blood loss in labor. Additionally, PGF2 has been linked to being naturally involved in the process of labor. It has been seen that there are higher levels of PGF2 in maternal fluid during labor when compared to at term. This signifies that there is likely a biological use and significance to the production and secretion of PGF2 in labor. Prostaglandin is also used to treat uterine infections in domestic animals.

<span class="mw-page-title-main">Calcium-activated potassium channel subunit alpha-1</span> Voltage-gated potassium channel protein

Calcium-activated potassium channel subunit alpha-1 also known as large conductance calcium-activated potassium channel, subfamily M, alpha member 1 (KCa1.1), or BK channel alpha subunit, is a voltage gated potassium channel encoded by the KCNMA1 gene and characterized by their large conductance of potassium ions (K+) through cell membranes.

<span class="mw-page-title-main">KCNA2</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily A member 2 also known as Kv1.2 is a protein that in humans is encoded by the KCNA2 gene.

<span class="mw-page-title-main">KCNMB1</span> Protein-coding gene in the species Homo sapiens

Calcium-activated potassium channel subunit beta-1 is a protein that in humans is encoded by the KCNMB1 gene.

<span class="mw-page-title-main">KCND3</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily D member 3 also known as Kv4.3 is a protein that in humans is encoded by the KCND3 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.

<span class="mw-page-title-main">KCNAB1</span> Protein-coding gene in the species Homo sapiens

Voltage-gated potassium channel subunit beta-1 is a protein that in humans is encoded by the KCNAB1 gene.

<span class="mw-page-title-main">KCNMB3</span> Protein-coding gene in the species Homo sapiens

Calcium-activated potassium channel subunit beta-3 is a protein that in humans is encoded by the KCNMB3 gene.

A uterotonic, also known as an oxytocic or ecbolic, is a type of medication used to induce contraction or greater tonicity of the uterus. Uterotonics are used both to induce labor and to reduce postpartum hemorrhage.

<span class="mw-page-title-main">Retosiban</span> Chemical compound

Retosiban also known as GSK-221,149-A is an oral drug which acts as an oxytocin receptor antagonist. It is being developed by GlaxoSmithKline for the treatment of preterm labour. Retosiban has high affinity for the oxytocin receptor and has greater than 1400-fold selectivity over the related vasopressin receptors

<span class="mw-page-title-main">Susan Wray</span> Cellular and molecular physiologist

Susan C. Wray is professor of cellular and molecular physiology at the University of Liverpool. She also serves as the President of the International Union of Physiological Sciences (IUPS) and is president of the Federation of European Physiological Societies (FEPS). She was the founding editor-in-chief of Physiological Reports. and is the first editor-in-chief of Current Research in Physiology. She serves as director of the centre of better births in Liverpool Women's Hospital which was opened in 2013 with funding of £2.5 million with the objective of basic scientists working together with clinicians on problems during pregnancy. Along with Zarko Alfirevic, she leads the Harris wellbeing preterm birth centre. Wray is the director of the University of Liverpool Athena SWAN and team leader for the institute of translational medicine. Her primary research interests are in smooth muscle physiology, reproductive medicine and cell signalling.

<span class="mw-page-title-main">Colin Nichols</span> English academic

Colin G. Nichols FRS is the Carl Cori Endowed Professor, and Director of the Center for Investigation of Membrane Excitability Diseases at Washington University in St. Louis, Missouri.

References

  1. 1 2 3 4 5 6 7 "Washington People: Sarah England". Washington University School of Medicine in St. Louis. 2017-09-26. Retrieved 2020-06-21.
  2. ↑ "Sarah England, PhD". Center for Reproductive Health Sciences. Retrieved 2020-06-21.
  3. 1 2 Osborn, J. W.; England, S. K. (December 1990). "Normalization of arterial pressure after barodenervation: role of pressure natriuresis". The American Journal of Physiology. 259 (6 Pt 2): R1172–1180. doi:10.1152/ajpregu.1990.259.6.R1172. ISSN   0002-9513. PMID   2260728.
  4. 1 2 3 England, S. K.; Wooldridge, T. A.; Stekiel, W. J.; Rusch, N. J. (May 1993). "Enhanced single-channel K+ current in arterial membranes from genetically hypertensive rats". The American Journal of Physiology. 264 (5 Pt 2): H1337–1345. doi:10.1152/ajpheart.1993.264.5.H1337. ISSN   0002-9513. PMID   8498547.
  5. 1 2 3 4 "Vanderbilt University Daily Register". news.vanderbilt.edu. Retrieved 2020-06-21.
  6. 1 2 3 4 England, S. K.; Uebele, V. N.; Shear, H.; Kodali, J.; Bennett, P. B.; Tamkun, M. M. (1995-07-03). "Characterization of a voltage-gated K+ channel beta subunit expressed in human heart". Proceedings of the National Academy of Sciences of the United States of America. 92 (14): 6309–6313. Bibcode:1995PNAS...92.6309E. doi: 10.1073/pnas.92.14.6309 . ISSN   0027-8424. PMC   41507 . PMID   7603988.
  7. 1 2 3 4 5 "Meet the researchers". www.marchofdimes.org. Retrieved 2020-06-21.
  8. ↑ "Sarah K. England, Ph.D. named Wolff Professor of Medicine - cimed.wustl.edu". cimed.wustl.edu. Retrieved 2020-06-21.
  9. ↑ "Dr. Sarah England, Ph.D." A WordPress Site. Retrieved 2020-06-21.
  10. ↑ "Sarah England | Iowa Biosciences Academy | Department of Biology | The University of Iowa". iba.biology.uiowa.edu. Retrieved 2020-06-21.
  11. 1 2 "Iowa Biosciences Academy" (PDF). iba.biology.uiowa.edu. Retrieved June 21, 2020.{{cite web}}: CS1 maint: url-status (link)
  12. 1 2 "Alumni Video Profiles | RWJF Health Policy Fellows". www.healthpolicyfellows.org. Retrieved 2020-06-21.
  13. 1 2 "England named Wolff Professor of Medicine | The Source | Washington University in St. Louis". The Source. 2015-02-11. Retrieved 2020-06-21.
  14. ↑ "Research". www.marchofdimes.org. Retrieved 2020-06-21.
  15. 1 2 "England Lab". Center for Reproductive Health Sciences. Retrieved 2020-06-21.
  16. ↑ "Regulation of BK Channels in Smooth Muscle". Center for Reproductive Health Sciences. Retrieved 2020-06-21.
  17. ↑ "Sensitivity to Oxytocin During Labor". Center for Reproductive Health Sciences. Retrieved 2020-06-21.
  18. 1 2 Frey, Heather A.; Tuuli, Methodius G.; England, Sarah K.; Roehl, Kimberly A.; Odibo, Anthony O.; Macones, George A.; Cahill, Alison G. (September 2015). "Factors Associated with Higher Oxytocin Requirements in Labor". The Journal of Maternal-Fetal & Neonatal Medicine. 28 (13): 1614–1619. doi:10.3109/14767058.2014.963046. ISSN   1476-7058. PMC   4377306 . PMID   25204333.
  19. 1 2 Reinl, Erin L.; Goodwin, Zane A.; Raghuraman, Nandini; Lee, Grace Y.; Jo, Erin Y.; Gezahegn, Beakal M.; Pillai, Meghan K.; Cahill, Alison G.; de Guzman Strong, Cristina; England, Sarah K. (August 2017). "Novel oxytocin receptor variants in laboring women requiring high doses of oxytocin". American Journal of Obstetrics and Gynecology. 217 (2): 214.e1–214.e8. doi:10.1016/j.ajog.2017.04.036. ISSN   1097-6868. PMC   5644384 . PMID   28456503.
  20. ↑ Ferreira, Juan J.; Butler, Alice; Stewart, Richard; Gonzalez-Cota, Ana Laura; Lybaert, Pascale; Amazu, Chinwendu; Reinl, Erin L.; Wakle-Prabagaran, Monali; Salkoff, Lawrence; England, Sarah K.; Santi, Celia M. (January 2019). "Oxytocin can regulate myometrial smooth muscle excitability by inhibiting the Na+ -activated K+ channel, Slo2.1". The Journal of Physiology. 597 (1): 137–149. doi:10.1113/JP276806. ISSN   1469-7793. PMC   6312452 . PMID   30334255.
  21. 1 2 "Chronodisruption as a Risk for Preterm Birth". Center for Reproductive Health Sciences. Retrieved 2020-06-21.
  22. 1 2 Martin-Fairey, Carmel A.; Zhao, Peinan; Wan, Leping; Roenneberg, Till; Fay, Justin; Ma, Xiaofeng; McCarthy, Ronald; Jungheim, Emily S.; England, Sarah K.; Herzog, Erik D. (June 2019). "Pregnancy Induces an Earlier Chronotype in Both Mice and Women". Journal of Biological Rhythms. 34 (3): 323–331. doi:10.1177/0748730419844650. ISSN   1552-4531. PMC   7408307 . PMID   31018734. S2CID   131777324.
  23. ↑ "Research themes". www.marchofdimes.org. Retrieved 2020-06-21.
  24. ↑ Dimes, March of. "March of Dimes Provides $3 Million in New Funding For Preterm Birth Research". www.prnewswire.com (Press release). Retrieved 2020-06-21.
  25. ↑ England, Sarah. "Minority Postdoctoral Research Fellowship".{{cite journal}}: Cite journal requires |journal= (help)
  26. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 "england sk - Search Results". PubMed. Retrieved 2020-06-21.
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