Phone: (706) 721-9796
Fax: (706) 721-7299
State University of New York at Geneseo, Geneseo, NY, BS in Biology, 1996
Albany Medical College, Albany, NY, MS and PhD in Cardiovascular Pharmacology, 2000
Medical College of Georgia, Augusta, GA, postdoctoral fellowship in Cardiovascular Biology and Physiology
2014-present Associate Professor, Department of Physiology, Augusta University, Augusta, GA
2013-2014 Associate Professor, Department of Medicine, Georgia Regents University, Augusta, GA
2011-2013 Assistant Professor, Department of Medicine, Georgia Health Sciences University, Augusta, GA
2011-present Associate member of the Department of Pharmacology and Associate member of the Vascular Biology Center
2008-2011 Assistant Professor, Vascular Biology Center, Medical College of Georgia, Augusta, GA
2006-2008 Instructor, Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA
2003-2006 Assistant Research Scientist, Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA
The overall goal of my laboratory is to better understand the molecular mechanisms that regulate blood pressure in males and females under both physiological and pathophysiological conditions, including hypertension. Traditionally, it has been assumed that blood pressure control and the basis of hypertension is the same in males and females; just the magnitude of the response differs. However, based on the vast number of differences that have been identified in cardiovascular physiology, pathophysiology, and pharmacology between the sexes, there is growing evidence to suggest that the pathways by which males and females develop cardiovascular and renal diseases may be distinct. Ongoing studies are focused on 3 pathways involved in blood pressure control and cardiovascular function: the renin angiotensin system (RAS), the nitric oxide (NO) pathway, and inflammation.
The primary research focus of my laboratory is to address gaps in our knowledge regarding the mechanisms controlling blood pressure under normal physiological conditions and in disease states in females. Hypertension affects ~33% of adults in the U.S. and is the most common independent risk factor for cardiovascular disease. While ~81% of hypertensive women are treated for their hypertension, fewer than ~50% achieve blood pressure controlled to recommended levels. This likely relates to the fact that although women account for ~53% of the hypertensive population, the majority of basic science research is performed only in males and representation of women in clinical trials for cardiovascular disease is well below 50%. The importance of increasing our understanding of physiology in females is underscored by recent NIH mandates to include a discussion of sex as a biological variable in all grant applications.
Recent studies in my laboratory have examined sex differences in blood pressure control with respect to three major pathways known to regulate cardiovascular health: the nitric oxide (NO) pathway and oxidative stress, the renin-angiotensin system (RAS), and inflammation. NO is a critical regulator of blood pressure and experimental and clinical data show that females have greater NO bioavailability than males. Despite well-documented sex differences in NO bioavailability, the mechanisms responsible for sex differences and the consequences of these sex differences on CV health were unknown. We published the first characterization of NOS in the kidney of hypertensive males and females; female spontaneously hypertensive rats (SHR) have greater renal NO bioavailability than males. Additional studies then examined 1) the mechanism driving sex differences in NO and 2) the physiological implication(s) of sex differences in NO. We found sex differences in renal medullary NOS are mediated by a sex hormone and BP dependent increase in NOS in females. In contrast, greater levels of oxidative stress and decreases in tetrahydrobiopterin contribute to lower renal NO in males. To further assess the contribution of NOS on blood pressure control, SHR were treated with the NOS inhibitor L-NAME. Consistent with our biochemical data, female SHR are more dependent on NOS to maintain blood pressure. Male SHR also exhibit impaired endothelium-dependent vasodilation and decreases in NO-dependent dilation compared to females. Current studies are examining the molecular mechanisms by which females maintain greater NO, including the role of sex hormones, maturation, and NOS cofactors.
Inhibitors of the RAS are among the most widely used drugs to treat hypertension irrespective of sex, despite numerous sex differences in the RAS. Our group has been critical in defining the molecular mechanisms driving sex differences in RAS activation. Our laboratory was the first to report that greater levels of the vasodilatory peptide Ang (1-7) antagonizes Ang II-induced increases in blood pressure in females and Ang (1-7) contributes more to the BP lowering effects of angiotensin receptor blockers in females. We further showed that greater Ang (1-7) levels occur via an ACE-dependent mechanism, in contrast to an expected role for ACE2. We have also begun to translate our findings to humans and recently reported that women have higher circulating Ang (1-7) levels than men. Ongoing studies are examining the role of the angiotensin type 2 (AT2) receptor on blood pressure control and immune cell activation in males compared to females.
There is growing appreciation in the field of hypertension that immune cells, in particular T cells, are critical for the development and maintenance of hypertension. Prior to 2012, all of the data supporting a role for immune cells had been collected using male experimental animals exclusively. Our laboratory reported for the first time that blood pressure in female SHR is sensitive to lymphocyte inhibition. We were also the first to report that male SHR have greater numbers of renal effector T cells, while females have more immuno-suppressive T regulatory cells (Tregs). Furthermore, either preventing increases in BP or lowering BP in SHR decreased Tregs only in females and abolished the sex difference. These data suggest a compensatory increase in Tregs in female SHR to limit increases in BP. Additional studies examined the impact of angiotensin (Ang) II on T cells in kidneys of male and female Sprague-Dawley (SD) rats. Although Ang II increased total renal T cells in both sexes, Tregs increased only in females. Ongoing studies are testing the hypothesis that this increase in Tregs in females is critical to the ability of females to maintain a lower blood pressure relative to males. We are also examining the contribution of T cells to high-fat diet-induced increases in blood pressure in females, the role of cell death in mediating T cell activation, and the mechanisms responsible for producing the sex difference in the renal T clel profile.
2017 Augusta University Faculty Senate Outstanding Faculty Award from The Graduate
2016 Augusta University Authentic Women Leaders Pilot Pipeline Program
2016 American Journal of Physiology - Regulatory, Comparative and Integrative Physiology Star Reviewer
2015 Chair, APS Sex and Gender-Related Research Interest Group
2014 Named the 2015 APS Renal Section Young Investigator
2013 Promoted with tenure
2013 Selected as Associate Editor for AJP:Renal Physiology
2013 Selected as Cardiorenal Study Section Co-Chair; American Heart Association
2013 Named Chair of the Augusta University Women’s Health Research Interest Group in the Div. of Clinical Translational Science
2011 Recipient of GHSU Outstanding Young Basic Science Faculty Award
2011 Recipient of GHSU Research Institute Emerging Scientist Award
2010 Named Fellow of the American Heart Association and the Council for High Blood Pressure Research
2007 Recipient of Consortium for Southeastern Hypertension Control Arthur Guyton New Investigator Award
2007 Named the APS Water and Electrolyte Homeostasis Section New Investigator
2008 Recipient of Kidney Council New Investigator Travel Award
2006 Recipient of Merck New Investigator Award
Tipton AJ, Musall JB, Crislip GR, Sullivan JC. Greater transforming growth factor-β in adult female SHR is dependent on blood pressure, but does not account for sex differences in renal T regulatory cells. Am J Physiol Renal Physiol, 2017, Epub ahead of print. DOI: 10.1152/ajprenal.00175.2017
Gillis EE and Sullivan JC. Sex Differences in Hypertension: Recent Advances. Hypertension, 68(6):1322-1327 2016. DOI: 10.1161/HYPERTENSIONAHA.116. 06602
Taylor L and Sullivan JC. Sex Differences in Obesity-Induced Hypertension and Vascular Dysfunction: A Protective Role for Estrogen in Adipose Tissue Inflammation? Am J Physiol Regu, 2016, Epub ahead of print. DOI: 10.1152/ajpregu.00202.2016
Sasser JM, Brinson KN, Tipton AJ, Crislip GR and Sullivan JC. Blood pressure, sex and female sex hormones influence renal inner medullary nitric oxide synthase activity and expression in Spontaneously Hypertensive Rats. J Am Heart Association. 4(4); pii: e0017382015, 2015. DOI: 10.1161/JAHA.114.001738
Tipton AJ, Baban B, Sullivan JC. Female SHR Have a Compensatory Increase in Renal Regulatory T Cells in Response to Elevations in Blood Pressure. Hypertension, 64(3):557-64; 2014. DOI: 10.1161/HYPERTENSIONAHA.114.03512