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Alexander - Biosketch

BIOGRAPHICAL SKETCH

NAME: Barbara T. Alexander
eRA COMMONS USER NAME (credential, e.g., agency login): BAlex7
POSITION TITLE: Professor
EDUCATION/TRAINING

 

Personal Statement

Dr. Barbara T. Alexander is a Professor of Physiology & Biophysics, at the University of Mississippi Medical Center in Jackson, MS where she serves as Core Leader for the NIH/COBRE Cadiorenal and Metabolic Diseases Research Center. In this capacity, she coordinates core services for analysis of numerous biochemical, analytical, molecular, histological and imaging core services. Dr. Alexander has served as the Director of the Bioanalytical Core since 2002, all while maintaining an active research program. She received her postdoctoral training at the University of Mississippi Medical Center in the laboratory of Dr. Joey Granger from 1997-2001 after which she was appointed as an Assistant Professor of Physiology & Biophysics in 2002 where she has risen to her current position as Professor of Physiology.
Dr. Alexander has a strong focus on research. For the past 26 years, her research has involved the study of renal mechanisms that contribute to blood pressure control. Investigation into the renal mechanisms that mediate hypertension that develops in pregnancies complicated by placental ischemia was initiated during her fellowship training years. Her interest in maternal-fetal medicine led to investigation into the inverse relationship between birth weight and blood pressure, an area of research now referred to as the developmental origins of health and disease. Dr. Alexander’s current research investigates the mechanisms that contribute to sex differences in blood pressure in low birth weight offspring, how aging affects the developmental programming of cardiovascular, renal and metabolic health across the lifespan, the etiology of IUGR and how maternal therapeutic interventions improve fetal growth and long-term chronic health in the offspring. She has a strong interest in mentoring and has served as a mentor to numerous trainees from the high school to the faculty level. She is a recent recipient of the Regions TEACH prize recognizing her excellence in teaching. Dr. Alexander has authored over 115 publications and she is currently funded by a R01 from the NIH. Her expertise in this area is highlighted by a recently released Scientific Statement from the American Heart Association:

Alexander BT, South AM, August P, Bertagnolli M, Ferranti EP, Grobe JL, Jones EJ, Loria AS, Safdar B, Sequeira-Lopez MLS; American Heart Association Council on the Kidney in Cardiovascular Disease; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; Council on Hypertension; and Council on Lifestyle and Cardiometabolic Health. Appraising the Preclinical Evidence of the Role of the Renin-Angiotensin-Aldosterone System in Antenatal Programming of Maternal and Offspring Cardiovascular Health Across the Life Course: Moving the Field Forward: A Scientific Statement From the American Heart Association. Hypertension. 2023 Mar 23. doi: 10.1161/HYP.0000000000000227. PMID: 36951054.

Ongoing and recently completed projects include:

Active

R01 143459 Alexander (PI) 12/01/2019-11/30/2023 NCE 11/30/2024 2.0 calendar NIH/NHLB $1,368,000

Hypertension in Adult IUGR Offspring: Beneficial Effects of Perinatal Intervention.
This grant will investigate the beneficial effect of maternal therapeutic interventions on fetal health. Role: Principle Investigator

P20 GM121334 Reckelhoff (PI) 6/1/2022 – 5/30/2027 2.4 calendar NIH/NIGMS $7,500,000

Mississippi Center of Excellence in Perinatal Research
This grant provides infrastructure and training support for junior investigators in the area of perinatal, pregnancy and fetal programming research.
Role: Basic Science Core Director, Mentor

P20 GM104357 Hall (PI) 7/1/2018 –4/30/2023 1.8 calendar NIH/NIGMS $7,497,565

Cardiorenal and Metabolic Diseases Research Center
This grant provides infrastructure and training support for junior investigators in the area of obesity and metabolic disease related research.
Role: Core Leader, Core B

Previous

R01 HL137791 George (PI) 7/1/2017 – 6/30/2022 0.6 calendar NIH/NHLBI $1,250,000

A novel therapy for preeclampsia
This grant investigated a novel therapy for the treatment of preeclampsia and benefit to the mother and her child.
Role: Co-Investigator

Positions, Scientific Appointments and Honors (selected):

2021- Director Research, Women’s Health Research Center, UMMC

2021 Interim Program Director, Graduate Program in Physiology, UMMC

2020 Reviewer, Fellowships: Physiology and Pathobiology of the Vascular and Hematological Systems

2019- Member, Awards Committee, Hypertension Council, American Heart Association

2018-2021 Associate Editor, Biology of sex Differences

2018-2021 Representative, Committee on Committees for Water and Electrolyte Homeostasis Section,

American Physiological Society

2018 Reviewer, Canadian Institutes of Health, Catalyst Grant: Sex as a Variable in Biomedical

Research

2017- Basic Science Core Director, Mississippi Center of Excellence in Perinatal Research

2017 Reviewer, Diabetic Complications Consortium

2017 Reviewer Medical Research Council, United Kingdom

2015 Reviewer, American Heart Association, Strategically Focused Hypertension Network Committee

2015 Reviewer, Health Research Council of New Zealand Funding Round

2014-2017 Elected Councilor, American Physiology Society

2014-2016 Chair, Membership Committee, Council for High Blood Pressure Research, American Heart

Association

2014 Reviewer, American Heart Association, Collaborative Science Award LOI Committee

2014- Professor, Department of Physiology, University of Mississippi Medical Center

2014- Director, Basic Research, Center of Excellence in Developmental Outcomes Research, UMMC

2013-2019 Member, NIH/NHLB Hypertension and Microcirculatory Study Section

2013 Reviewer, Hartstichting, Dutch Heart Foundation

2013 Chair, American Heart Association Cardiorenal Basic Science Study Section

2012- Member, Editorial Board, American Journal of Physiology, heart and Circulatory Physiology

2011-2013 Editor, Council for High Blood Pressure Research Connections Newsletter, American Heart

Association

2011-2016 Member, Leadership Committee, Council for High Blood Pressure, American Heart Association

2011-2014 Secretary/ Treasurer, Water and Electrolyte Homeostasis Section, American Physiological Society

2011- Member, Editorial Board, American Journal of Physiology, Renal Physiology

2009-2012 Associate Editor, Gender Medicine

2008-2013 Member, American Heart Association Cardiorenal Basic Science Study Section

2007-2014 Associate Professor, Department of Physiology, University of Mississippi Medical Center

2006- Abstract Grader, Hypertension Council, American Heart Association

2005- Member, Editorial Board, Hypertension

2005- Member, Editorial Board, American Journal of Physiology, Regulatory, Integrative and

Comparative

2005 Reviewer, Israel Science Foundation

2002-2007 Assistant Professor, Department of Physiology, University of Mississippi Medical Center

2002- Director, Analytical and Assay Core, Department of Physiology, UMMC

1999-2001 Instructor, Department of Physiology, University of Medical Center

Honors (Selected):

2023 Regions TEACH Prize

2023 Norman C. Nelson Excellence in Teaching Order

2021 Billy S. Guyton Distinguished Professorship, UMMC

2019 School of Graduate Studies in the Health Sciences Distinguished Alumna

2019 UMMC/GWIMS Innovation Award, Group on Women in Medicine and Science

2018 Harriet Dustan Award, AHA Council on Hypertension

2015 Excellence in Research Award, Platinum Level, UMMC

2015 Fellow, American Physiological Society

2014 Elected Basic Science Faculty Member, Alpha Omega Alpha

2007 Arthur Guyton New Investigator Award, COSEHC.

2005 New Investigator Award, Water and Electrolyte Section, American Society of Physiology,

2004 Excellence in Research Award, Gold Level, UMMC

2004 FASEB Summer Research Conference Travel Stipend Recipient, Renal Microcirculatory and Tubular Dynamics: Molecules to Man

2003 American Society of Hypertension / Monarch Pharmaceuticals Young Scholar Award

2003 Fellow, American Heart Association, Council for High Blood Pressure Research

2001 The Inter-American Society of Hypertension Travel Award, Santiago, Chile

2000 American Society of Hypertension/Bristol Myers Squibb Recognition Awards for Young Investigators

in Training

2000 Caroline tum Suden/Frances A. Hellebrandt Professional Opportunity Award, American Physiological

Society

1999 Merck New Investigator Award: Excellence in High Blood Pressure Research, American Heart Assoc.

Contributions to Science

Link to full list of published work:

https://www.ncbi.nlm.nih.gov/myncbi/16yCpyenfR4kc/bibliography/public/

Dr. Alexander’s research has focused on the renal mechanisms that contribute to altered blood pressure control during pregnancies complicated by placental ischemia, and in offspring born low birth weight.

1) Placental ischemia and hypertension during pregnancy

The focus of my research in my early career involved investigation into the renal mechanisms that contribute to the development of hypertension during pregnancy. My work in a rat model of reduced uterine perfusion demonstrated that placental ischemia was sufficient to induce hypertension during pregnancy in the rat. These studies also initiated investigation into the importance of inflammatory cytokines such as TNF-alpha, in the etiology of hypertension during pregnancy. My body of work during my fellowship training with Dr. Granger also noted the important contribution of the vasoactive factors endothelin and nitric oxide in pregnancies complicated by hypertension. In addition, my laboratory developed the RUPP model of placental ischemia in the mouse which will allow the use of genetically modified mouse models to be incorporated with the model of placental ischemia to further investigate the etiology of hypertension during pregnancy and intrauterine growth restriction on later chronic health. Selected publications from my fellowship and a more recent in the field of preeclampsia:

1. Alexander BT, Kassab SE, Miller MT, Abram SR, Reckelhoff JF, Bennett WA, and Granger JP. Reduced uterine perfusion pressure during pregnancy in the rat is associated with increases in arterial pressure and changes in renal nitric oxide. Hypertension, 2001;37(4):1191-1195.
2. Alexander BT, Rinewalt AN, Cockrell KL, Bennett WA, and Granger JP. Endothelin type A receptor blockade attenuates the hypertension in response to chronic reductions in uterine perfusion pressure. Hypertension, 2001;37(2 Part 2):485-489.
3. Alexander BT, Cockrell KL, Massey M.B, Bennett WA, and Granger JP. Tumor necrosis factor-alpha induced hypertension in pregnant rats results in decreased renal neuronal nitric oxide synthase expression. Am J Hypertens, 2002;15(2 Pt 1):170-175.
4. Intapad S, Warrington JP, Spradley FT, Palei AC, Drummond HA, Ryan MJ, Granger JP, Alexander BT. Reduced uterine perfusion pressure induces hypertension in the pregnant mouse. Am J Physiol Regul Integr Comp Physiol. 2014; 307(11):R1353-R1357.

Low birth weight and blood pressure

My interest in placental ischemia noted a consistent finding, that placental ischemia resulted in intrauterine growth restriction (IUGR) or low birth weight. This observation set the stage for my independent studies in thearea of developmental programming of adult health and disease. My initial studies investigating the link between birth weight and blood pressure quickly noted a role for the renal nerves in the etiology of hypertension that develops in male growth restricted rat offspring. We were the first laboratory to report that the renal nerves are a contributory factor to the developmental programming of hypertension and we further elucidated their importance in the development and maintenance of sustained increases in blood pressure in male growthrestricted rats. We also noted temporal changes in the renin angiotensin followed fetal exposure to placental ischemia and that the RAS was also a major contributor to the etiology of IUGR-induced hypertension in male growth restricted rats. My laboratory has consistently been a major contributor to in-depth mechanistic investigation into the etiology of hypertension following a developmental insult. Although our early studies focused on male growth-restricted offspring in young adulthood, our studies noted that sex steroids contribute to the developmental programming of increased cardiovascular/renal risk. Thus, more recent studies in my laboratory focus on sex differences as outlined in my next contribution topic. Early studies from my laboratory:

1. Alexander, BT. Placental insufficiency leads to development of hypertension in growth restricted offspring. Hypertension, 2003;41(3):457-462.
2. Alexander BT, Hendon AE, Ferril G, Dwyer TM. Renal denervation abolishes hypertension in low birth weight offspring from pregnant rats with reduced uterine perfusion. Hypertension, 2005, 45(2):754-758.
3. Grigore D, Ojeda NB, Robertson EB, Dawson AS, Huffman C, Bourassa E, Speth RC, Brosnihan, KB, Alexander BT. Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring. Am J Physiol Regul Integr Comp Physiol. 2007;293(2):R804-R811.
4. Ojeda NB, Royals TP, Black JT, Dasinger JH, Johnson JM, Alexander BT.Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring.Am J Physiol Regul Integr Comp Physiol. 2010; 298:1421-1427.

Sex differences in the developmental programming of blood pressure

The model of IUGR induced by placental ischemia in the rat results in hypertension in male growth-restricted rats in young adulthood whereas age-matched female growth restricted rats are normotensive. Thus, early on inmy career my research focus shifted towards a strong interest into the mechanisms that contribute to the sexspecific programming of hypertension following a developmental insult with a particular focus on sex steroids. Hypertension in male growth restricted rats in testosterone dependent whereas estrogen is protective against increased blood pressure in female growth restricted rats during young adulthood. Modulation of the RAS by sex steroids is one potential mechanism that contributes to the etiology of hypertension that develops in male low birth weight offspring and my laboratory also noted that modulation of the RAS by ovarian hormones is protective against the development of hypertension in female low birth weight offspring in young adulthood. A sex- specific role for oxidative stress is indicated with male growth restricted rats exhibiting an increase in renal markers of oxidative stress whereas female growth restricted rats exhibiting an increase in renal antioxidant capabilities. The role of endothelin and the response to a secondary hit are also sex-specific in IUGR offspring from RUPP dams. My laboratory continues to be a leader in the field of study related to sex differences in the developmental programming of hypertension.

1. Ojeda NB, Hennington BS, Williamson DT, Hill ML, Betson NE, Sartori-Valinotti JC, Reckelhoff JF, Royals TP, Alexander BT. Oxidative stress contributes to sex differences in blood pressure in adult growth-restricted offspring. 2012: 60:114-122.
2. Ojeda NB, Royals TP, Alexander BT.Sex differences in the enhanced responsiveness to acute angiotensin II in growth-restricted rats: Role of fasudil, a Rho kinase inhibitor.Am J Physiol Renal Physiol. 2013;304(7):F900-F907.
3. Intapad S, Ojeda NB, Varney ET, Royals TP, Alexander BT. Sex-specific effect of endothelin in the blood pressure response to acute angiotensin II in growth-restricted rats. 2015;66:1260-1266.
4. Intapad S, Dasinger JH, Johnson JM, Brown AD, Ojeda NB,, Alexander BT. Male and female intrauterine growth-restricted offspring differ in blood pressure, renal function , and glucose homeostasis responses to a postnatal diet high in fat and sugar. Hypertension, 2019;73(3):620-629.

Postnatal influences and age on developmental programming of hypertension and chronic disease.

Adverse environmental influences during early life can also lead to an increased risk for cardiovascular, renal and metabolic disease. Thus, my research interests in the developmental origins of chronic disease recentlyfocused on investigation into the mechanisms by which adverse influences in early postnatal life such as overnutrition or age alter cardiovascular and metabolic health in offspring. My laboratory recently noted that female growth-restricted rats that are normotensive in early adulthood, develop a significant increase in blood pressure in later life that is mediated by sex steroids, the renal nerves, and the renin angiotensin system. IUGR also programs a sex- and age-specific increase in metabolic risk and renal injury in growth-restricted offspring from RUPP dams. Additionally, other averse influences during prenatal life can also program increased cardiovascular risk. Polycystic Ovary Syndrome (PCOS), a syndrome associated with increased androgens and metabolic diseases in women, affects over 10% of the female population. We recently reported that female offspring of PCOS dams may be protected from cardiovascular risk but exhibit enhanced renal risk in adult life.

1. Davis GK, Newsome AD, Cole A, Ojeda Newsome AD, Davis GK, Adah ON, Ojeda NB, Alexander BT. Chronic estrogen supplementation prevents the increase in blood pressure in female growth-restricted offspring at 12 months of age. Hypertension 2019; 73(5):1128-1136.
2. Newsome AD, Davis GK, Adah ON, Ojeda NB, Alexander BT. Renal injury after uninephrectomy in male and female intrauterine growth-restricted aged rats. PLOS ONE, 2019; 14(3):e0213404.
3. Davis GK, Intapad S, Newsome AD, Coats LE, Bamrick DR, Ojeda NB, Alexander BT. Androgen receptor blockade differentially regulates blood pressure in growth-restricted versus ovarian deficient rats. 2019 Oct;74(4):975-982.
4. Shawky NM, Dalmasso C, Ojeda NB, Zuchowski Y, Stachenfeld N, Alexander BT, Reckelhoff JF. Consequences of hyperandrogenemia during pregnancy in female offspring: attenuated response to angiotensin II. J Hypertens. 2022;40(4):712-722.

The etiology of IUGR and maternal interventions in preeclampsia, benefit versus harm in the fetus.

Despite over 50 years of research, there are no effective therapeutics to prevent PE and/or IUGR. Early delivery remains the only treatment. However, early delivery can result in preterm or low birth weight, which also places an individual at risk for increased blood pressure. Due to my background in preeclampsia and IUGR-induced hypertension in the offspring,the recent focus of my researchhas involved the study of the etiology of IUGR thatdevelops in response to placenta ischemia coupled to identification of therapeutic targets to improve maternaland fetal health in preeclampsia. In conjunction with collaborators, my research has initiated studies focused on the identification of novel targets in the treatment and prevention of IUGR. My first studies, funded by my R56, investigated the importance of soluble guanylate cyclase as a potential mediator of impaired fetal growth in response to placental ischemia. My current research funded by my R01 involves not only the mechanisms that contribute to the etiology of IUGR that develops in response to placental ischemia including the importance of microRNAs, but also explores the benefit of potential targets to attenuate IUGR in pregnancies complicated by preeclampsia.

1. Coats LE, Bakrania B, Bamrick-Fernandez D, Ariatti AM, Rawls AZ, Ojeda NB, Alexander BT. Soluble guanylate cyclase stimulation in late gestation does not mitigate asymmetric intrauterine growth restriction or cardiovascular risk induced by placental ischemia in the rat. Am J Physiol Heart Circ Physiol. 2021;320(5):H1923-H1934.
2. Coats LE, Bamrick-Fernandez DR, Ariatti AM, Bakrania BA, Rawls AZ, Ojeda NB, Alexander BT. Stimulation of Soluble Guanylate Cyclase Diminishes Intrauterine Growth Restriction in a Rat Model of Placental Ischemia. Am J Physiol Regul Integr Comp Physiol. 2021;320(2): R149-R161.
3. Ashraf UM, Hall DL, Rawls AZ, Alexander BT. Epigenetic processes during preeclampsia and effects on fetal development and chronic health. Clin Sci (Lond). 2021;135(19):n2307-2327.
4. Ashraf UM, Hall DL, Campbell N, Waller JP, Rawls AZ, Solise D, Cockrell K, Bidwell GL 3rd, Romero DG, Ojeda NB, LaMarca B, Alexander BT. Inhibition of the AT1R agonistic autoantibody in a rat model of preeclampsia improves fetal growth in late gestation. Am J Physiol Regul Integr Comp Physiol. 2022. 323(5):R670-R681.