Epigenomics of Hypertension
Dr. Liang directs one of the four centers in the nation that form the American Heart Association Strategically Focused Hypertension Research Network. The center consists of basic, clinical, and population science projects led by Dr. David Mattson, Dr. Srividya Kidambi, and Dr. Theodore Kotchen, working with Dr. Cowley, Dr. Pengyuan Liu, and other investigators. The three projects are collectively testing the hypothesis that lifestyle factors and gene-environment interactions cause genome-wide changes in DNA methylation, which contribute to the development of hypertension and can be used as predictive or diagnostic markers of hypertension and related diseases.
The proposed Center will offer several unique values and strengths. It will explore a broad, novel area of hypertension research, which could drive hypertension research to advance in new directions in the next decade and beyond. It will build on substantial expertise in diverse disciplines and cutting-edge technologies available in a group of key investigators at a single location (MCW) with a long history of successful collaboration in hypertension research.
Specific Aims:
- The basic science project will use the Dahl salt-sensitive rat model to examine the effects of maternal dietary exposure and dietary salt intake on DNA methylation changes in T cells and whether such effects contribute to the development of hypertension.
- The clinical project will utilize two approaches (identical twins and defined changes in dietary salt intake) to examine the effects of lifestyle factors, including dietary salt intake on epigenomic changes in T cells in human subjects, and whether such effects can reveal potential mechanisms of hypertension.
- The population project will analyze blood cell DNA samples collected approximately 15 years ago from a local, well-phenotyped African American population and investigate whether DNA methylation patterns in these historic samples were associated with levels of blood pressure at the time of DNA collection and could predict the development of hypertension and related cardiovascular events over the subsequent years.
What is the major problem being addressed by this study?
Hypertension is the No. 1 identifiable cause of death worldwide according to reports from the World Health Organization in 2009. However, our understanding of how hypertension develops is incomplete, and blood pressure is one of the most notable examples in which DNA sequence variations that have been identified account for only a very small fraction of the variation of the trait. The lack of a thorough understanding of the molecular basis for hypertension is a major obstacle to developing more effective approaches for controlling hypertension.
What specific questions are you asking and how will you attempt to answer them?
We asked whether epigenetic modifications, specifically changes in genome-wide DNA methylation, would contribute to hypertension. Hypertension in most cases is the result of interactions between DNA and environmental factors, including diet and other lifestyle choices. These interactions often lead to changes in epigenetic modifications. We will attempt to answer the question by examining the role of DNA methylation in an animal model of hypertension, monozygotic twins with discordant blood pressure levels, human subjects exposed to a low sodium intake, and a population of African Americans who are at higher risk of developing hypertension and hypertension-related cardiovascular diseases.
Overall, what is the potential impact of this work to the mission of the AHA?
While a significant role of epigenetic modifications in the development of hypertension is strongly supported by numerous studies, very few studies have examined epigenetic modifications in hypertension at the genome or near-genome scale, and none has done so systematically in animal models and human subjects. We, therefore, anticipate that the proposed study will lead to a wide range of new discoveries, providing a novel basis for developing new approaches for controlling hypertension and driving hypertension research to advance in new directions in the next decade and beyond.
Basic Project
Lay Summary
- What is the major problem being addressed by this study? Cardiovascular diseases were the underlying cause in 1 of 3 deaths in the US in 2007-10. Hypertension is a major risk factor for cardiovascular disease. The present studies will be performed in the Dahl SS rat, an animal model with disease phenotypes similar to those observed in salt-sensitive human hypertension. These studies will be performed to understand the factors which lead to salt-sensitive hypertension and renal disease.
- What specific questions are you asking and how will you attempt to answer them? Essential hypertension is the result of interactions between genetic background and environment. Hypertension is a notable example in which alterations in genetic sequence account for a small fraction of the disease trait. This missing heritability may be due to epigenetic changes (chemical modifications of DNA in the absence of alterations in genetic sequence). The present studies will elucidate the role of epigenetic changes, mediated by changes in the environment, in salt-sensitive hypertension and renal damage.
- Overall, what is the potential impact of this work to the mission of the AHA? You might address: What is the long-term biomedical significance of your work, particularly as it pertains to the cardiovascular area? What major therapeutic advance(s) do you anticipate that it will lead to? For instance, new drug(s), a surgical technique/procedure, a diagnostic tool/test, a previously undetected risk factor, etc?
This goal of this work, as well as that of the other projects in the Hypertension Network Proposal, is to understand the role of epigenetics (chemical modifications of DNA in the absence of sequence changes) in the development of disease. All three projects will contribute to achieving this common, central goal by studying the effect of dietary and lifestyle factors on the development of hypertension. Together, these projects will mechanistically define and study this biological problem while translating the observations to human health. The ultimate outcome is to determine the mechanistic basis by which deleterious environmental factors affect cardiovascular health, with the goal of prediction and prevention of these adverse events.
Scientific Summary
Experiments in animals and human data indicate that the immune system is important in the development of hypertension and kidney damage and provides a link between the environment and disease. In this proposal, we present preliminary data, obtained with embryo transfer techniques, demonstrating that sodium-independent changes in the diet, mediated in the maternal environment, can profoundly attenuate sodium-sensitive hypertension and renal disease phenotypes in adult offspring of Dahl Salt Sensitive (SS) rats. A subsequent genome-scale methylation analysis demonstrated significant differences in methylation of circulating T lymphocytes and renal outer medullary tissue in rats from mothers fed different diets. Further studies demonstrated that selective knockdown of DNMT3A, an enzyme that catalyzes de novo methylation of DNA, amplified hypertension in SS rats. These novel data indicate that epigenetic alterations in immune cells, resulting from an altered maternal environment, can profoundly impact salt-sensitive hypertension and renal damage. The present studies are designed to examine the importance of DNA methylation in immune cells in the progression of disease in SS rats. This project will test the general hypothesis that the maternal dietary environment alters the epigenomic program in immune cells in SS rats and their de novo methylation response to an increased salt intake in adult life, which in turn affects immune cell infiltration and activation in the kidney and modifies salt-sensitive hypertension and renal disease. This hypothesis will be tested in three integrated aims.
Aim 1 will test the hypothesis that the maternal environment alters DNA methylation, RNA expression, immune cell phenotypes, and disease phenotypes in adult SS rats.
Aim 2 will test the hypothesis that the hematopoietic cell compartment plays a role in the determination of the SS disease phenotype, which is associated with epigenomic modifications in these cells.
Aim 3 will test the hypothesis that de novo DNA methylation causally contributes to SS hypertension and renal damage. This hypothesis may provide an important link between the environment and disease and help explain the “missing heritability” in hypertension. These integrative aims will address this hypothesis with unique experimental approaches including novel genetically-manipulated animal models, embryo transfer experiments, base-resolution mapping of DNA methylation, RNA-Seq, and bone-marrow transfer studies.
Twin Study
Are you an identical twin located around Milwaukee, Wisconsin?
If yes, you and your twin may be eligible to participate in a research study being conducted at the Medical College of Wisconsin.
The purpose of this research study is to understand causes of high blood pressure.
For more Information, please contact
Phone: 414-955-7438
High blood pressure is very common and is an important risk factor for heart and kidney diseases. We know that high blood pressure is genetic and runs in families. In addition to genes, factors such as diet, exercise, and other environmental factors can also influence blood pressure levels, perhaps by interacting with genes. Our research is aimed at understanding if and how the environment modifies the genetic material and whether these changes influence blood pressure levels in human subjects.
We intend to study identical twins to understand how genetic modifications (also known as epigenetic modifications), induced by environment, influence blood pressure (BP) levels in human subjects. Identical co-twins are expected to have same DNA at birth. However, if any modifications are noted in the DNA later on, it is presumed to be from the effect of the environment. We will analyze and compare DNA modifications in identical co-twins and their association with blood pressures.
We hope that findings of our study will help us understand whether genetic modifications, presumably caused by environmental factors, affect diseases such as hypertension and/or cardiovascular disease. Identification of specific modifications will allow us to develop targeted treatments for hypertension and/or cardiovascular disease.
Salt Study
Do you have increased blood pressure?
If yes, you may be eligible to participate in a research study being conducted at the Medical College of Wisconsin.
The purpose of this research study is to understand the effect of salt on high blood pressure.
For more Information, please contact
Phone: 414-955-7438
High salt in one’s diet is an important risk factor for high blood pressure and heart and kidney diseases. It is felt that salt may influence certain genes to influence blood pressure levels. Our research is aimed at understanding if and how the salt in the diet modifies the genetic material and whether these changes influence blood pressure levels in human subjects.
We intend to study individuals with mildly elevated blood pressures (with BP > 130/80 mm Hg and on 0-2 medications to treat high blood pressure). Subjects will be asked to go on 2 weeks of low-salt diet (we will provide the low salt diet at no cost to you). We will take measurements before and after the low-salt diet. We will analyze and compare DNA modifications in identical co-twins and their association with blood pressures.
We hope that findings of our study will help us understand how salt affects blood pressure.
Epigenetic Abstract:
Background Despite strong evidence for heritability of hypertension, this has not been accounted for by causative genetic mutations. One explanation for this “missing heritability” may be related to environmental modification of gene expression. In an earlier NIH-funded study, we evaluated blood pressure-related phenotypes and obtained DNA in 3,000 African Americans, 50% of whom were hypertensive. This cohort constitutes our current study population.
Hypothesis and Aims
Our central hypothesis is that differences in genome-wide DNA methylation patterns (markers of epigenetic modification) are associated with hypertension at baseline and predict the development of cardiovascular/renal disease over a 8-20 year period, independent of other CVD risk factors. The primary endpoint is a combined endpoint consisting of fatal or non-fatal myocardial infarction, fatal or non-fatal stoke, renal dialysis or transplantation, cardiovascular death.
Methods
We anticipate obtaining follow-up information in 800 subjects of the original cohort. Once identified, subjects will be asked about interim medical history and invited to attend a single outpatient visit to obtain standardized measurements of blood pressure, weight, height, and waist circumference. In instances where individuals cannot be located, we will search the National Death Index (NDI) to determine if a death has been recorded. NDI data also include cause of death. Genome-wide baseline DNA methylation analysis will utilize Reduced Representation Bisulphite Sequencing.
Data Analysis
Based on DNA and baseline blood pressures, DNA methylation patterns will be compared in normotensive and hypertensive subjects. We will also determine if methylation patterns at baseline are predictive of subsequent cardiovascular/renal events that are not otherwise accounted for by recognized risk factors.
Significance
Identifying associations of altered DNA methylation patterns with hypertension and hypertension-related cardiovascular/renal endpoints may direct future investigation of pathophysiological pathways by which gene-environment interactions contribute to these disorders.
Publications:
Touyz RM, Montezano AC, Rios F, Widlansky ME, Liang M. Redox stress defines the small artery vasculopathy of hypertension: How do we bridge the bench-to-bedside gap? Circ Res (in press)
Abstracts:
Abais-Battad JM, Liu P, Mattson DL, Liu Y, Cowley AW Jr, Kurth TM, Yang C, Lund H, Geurts AM, Kidambi S, Kotchen TA, Liang M. Dietary Salt and Non-Salt Components Have Substantial Effects on Genome-Wide DNA Methylation Patterns in Dahl SS Rats. Hypertension 68:AP136, 2016.
Erwin T Cabacungan ET, Geurts AM, Mattson DL, Liang M. Maternal Diet Leads to Nephron Count Differences After Postnatal Day 14 and Time-dependent Differences in Apoptosis and Unfolded Protein Response in Dahl Salt-Sensitive Rats. Hypertension. 68:A105, 2016.
Kidambi S, Li Y, Liu P, Leittl ML, Coly G, Cowley AW, Kotchen TA, Liu Y, Rockwell CE, Klump KL, Burt SA, Gernaat EP, Donohue MF, Rayamajhi S, Watson RE, Mattson DL, Liang M. DNA Methylation and Differences in Blood Pressure Levels in Monozygotic Twins. Hypertension. 68:AP264, 2016.
Li Y, Kidambi S, Liu P, Leittl ML, Liu Y, Mattson DL, Cowley AW, Kotchen TA, Liang M. Stability of DNA Methylation Profiles in Human DNA Samples in Long Term Storage. Hypertension 68:AP139, 2016.
Abais-Battad JM, Lund H, Mattson DL. Deletion of Rag1 Prevents High Dietary Protein-Induced Exacerbation of Hypertension and Renal Injury in Dahl SS Rats. Experimental Biology 2016.
Meet the Fellows
Yingchuan Li, M.D., Ph.D.
Department of Physiology and Center of Systems Molecular Medicine
Medical College of Wisconsin
8701 Watertown Plank Road
Milwaukee, WI 53226
EDUCATION
- 2015.07-now | Post-doctor | Medical College of Wisconsin
- 2011.09-2014.06 | Ph.D of Anesthesiology | Medical college of Shanghai Jiaotong University, Shanghai, China
- 1998.09-2002.06 | Master’s Degree of Anesthesiology | Medical college of Fudan University, Shanghai, China
- 1989.09-1995.06 | M.B. | Shanghai Medical College, Shanghai, China
Training and Positions
- 1/2015 – present | Project Appointment | Department of Physiology and Center of Systems Molecular Medicine Medical College of Wisconsin
- 11/2006 – present | Associate Chief Anesthesiologist
- 11/2004 – 10/2006 | Department of Anesthesiology&ICU, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University
- 11/2004 – 10/2006 | Anesthesia Attending | Department of Anesthesiology&ICU, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University
- 7/2007 – 10/2004 | Emergency Attending | Department of Emergency, Shanghai Zhongshan Hospital Affiliated to Fudan University
- 7/1999 – 6/2000 | Emergency Chief Resident | Department of Emergency, Shanghai Zhongshan Hospital Affiliated to Fudan University
- 7/1995 – 6/1999 | Emergency Resident | Department of Emergency, Shanghai Zhongshan Hospital Affiliated to Fudan University
Selected Publications
- Li YC, Cao YM, Zeng Z, Liang MF, Xue Y, Xi CH, Zhou M, Jiang W. Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis prevents lipopolysaccharide-induced apoptosis of pulmonary microvascular endothelial cells by inhibiting JNK/NF-κB pathways. Sci Rep. 2015; 3; 5: 8209
- Li YC, Zeng Z, Li Y, Huang W, Zhou M, Zhang X, Jiang W. Angiotensin-converting enzyme inhibition attenuates lipopolysaccharide-induced lung injury by regulating the balance between angiotensin-converting enzyme and angiotensin-converting enzyme 2 and inhibiting mitogen-activated protein kinase activation. Shock. 2015; 43(4):395-404
- Zhen Zeng, Ying-Chuan Li, Zhi-Hua Jiao, Jun Yao, and Ying Xue. The Cross Talk between cGMP Signal Pathway and PKC in Pulmonary Endothelial Cell Angiogenesis. Int J Mol Sci. 2014; 15(6): 10185–10198.
- Li YC, Xi CH, An YF, Dong WH, Zhou M*. Perioperative inflammatory response and protein S-100β concentrations-relationship with post-operative dysfunction in elderly patients. Acta Anaesthesiol Scand. 2012; 56(5): 595-600.
- Zhen Zeng#, Yingchuan Li#, Zhen Jiang, Chunsheng Wang, BingBing Li,WeiJiang. The Extracellular Signal-Regulated Kinase Is Involved in the Effects of Sildenafil on Pulmonary Vascular Remodeling. Cardiovascular Therapeutics. 2010; 28: 23-29. (Co-author) [JIANG Zhen, CAO Yong-mei, ZENG Zhen, Gu Yu-chun, JI Ying-ying, ZHAO Yu-peng, LI Ying-chuan*. Regulation of hypoxia response element-mediated Bcl-2-shRNA on hypoxia-induced anti-apoptotic pulmonary vascular endothelial cells. Journal of Shanghai Jiaotong University (Medical Science) 2015; 35(5): 674-678. (Corresponding author)
- Chao yongmei, Li yingchuan*. MicroRNA:A novel regulatory molecule in acute lung injury. Journal of Shanghai Jiaotong University (Medical Science) 2014; 34(10): 1539-1542. (Corresponding author)
- Li yachun, Li yingchuan*, Zhou ming, Jiang wei. Effects of lipolysaccharide on expression of ACE and ACE2 in rat pulmonary microvascular endothelial cells and intervention effects of angiotensin converting enzyme inhibitor. Journal of Shanghai Jiaotong University (Medical Science) 2012; 32(4): 452-457. (Corresponding author)
- Li yingchuan, Jiang wei, Zhou ming, Xue ying, Li yachun. Improvement of method for primary cultivation and identification of rat pulmonary microvascular endothelial cells. Journal of Shanghai Jiaotong University (Medical Science) 2010; 30(11): 1440-1443.
- Li yingchuan, An yifan, Dong weihua, Zhou ming. Correlation between post-operative congnitive dysfunction and peri-operative inflammation in elderly patients undergoing total hip replacement surgery. Shanghai Medical Journal. 2011; 34(4): 249-252.
- Li yingchuan, Zhou ming, Dong weihua, Tang wenqi, Sun zhan. Risk Factors of Prognosis of Acquired Septicemia from SICU: A Clinical Analysis. Chinese Journal of Nosocomiology. 2010; 20(18): 2765-2767.
- Li yingchuan, Zhou ming, Dong weihua, Tang wenqi, Sun zhan. Risk Factors of Prognosis of Acquired Septicemia from SICU: A Clinical Analysis. Chinese Journal of Nosocomiology. 2010; 20(18): 2765-2767.
- Li yingchuan, Jiang zhen, Jin xianghua, Luo hong, Guo kefang. Protective effect of ulinastatin on pulmonary function during cardiopulmonary bypass. J Clin Anesthesiol. 2004; 20(2): 69-72.
- Li yingchuan, Jiang zhen. Ulinastatin, a Human Protease Inhibitor, Attenuates Ischemia reperfusion Lung Injury. Journal of Fudan University (Medical Science) 2004; 31(2): 182-185.
Research Grants
- Title: The regulation of local ACE2-Ang(1-7)-Mas receptor axis and signal transduction mechanisms during Acute lung injury. Agency: National natural Science Foundation of China. 2012
- Title: The regulation effects of Ang-ACE system and intracellular signal transduction mechanisms during acute lung injury. Agency: Scientific Research Fundation of Shanghai Public Health Bureau. 2009
John Henry Dasinger, Ph.D.
Department of Physiology and Center of Systems Molecular Medicine
Medical College of Wisconsin
8701 Watertown Plank Road
Milwaukee, WI 53226
- 414-955-7415
- jhdasinger@mcw.edu
EDUCATION
- 2005 – 2009 | The University of Connecticut, Storrs, Connecticut
- 2009 | B.S., Biological Sciences
- 2011 – 2012 | The University of Mississippi Medical Center Jackson, Mississippi M.S. | Biomedical Sciences, 2012
- 2012-2016 | The University of Mississippi Medical Center Jackson, Mississippi Ph.D. | Physiology and Biophysics, 2016
Professional Memberships
- 2013-Present | American Physiological Society
- 2014-Present | American Heart Association
- 2014-Present | American Society of Nephrology
Awards/Honors
- Robert A. Maffaffey Memorial Award Recipient, UMMC, 2016
- Associated Student Body Student of the Year, UMMC, 2015-2016
- WEH Section Predoctoral Award Finalist, Experimental Biology 2016, San Diego, CA
- APS Abstract Travel Award, Cardiovascular, Renal and Metabolic Disease: Physiology and Gender, November 2015
- Graduate School Research Day Poster Presentation Award, UMMC, October 2015
- AHA Poster Competition Award Winner, September 2015, Washington DC
- WEH Section Predoctoral Award Finalist, Experimental Biology 2015, Boston, MA
- APS Professional Skills Training Course: Writing and Reviewing for Scientific Journals, Orlando, FL, January 2015
- APS Professional Skills Training Course Travel Stipend Recipient, Professional Integrity: Best Practices for Publishing Your Work, Orlando, FL, January 2014. Graduate School Research Day Poster Presentation Award, UMMC, October 2013
Service
Departmental/Institutional:
- President, Graduate Student Body, UMMC 2015-2016
- Student Alumni Representative (STAR), UMMC 2015-2016
- Alumni Affairs Liaison Chair, Associated Student Body, UMMC 2015-2016
- Co-Leader, Physiology In Training Journal Club, UMMC 2015-2016
- Treasurer, Graduate Student Body, UMMC 2014-2015
- Team Leader, Discovery U Outreach: Department of Physiology, 2014, 2015, 2016
- Participant, Project REACH, UMMC/ Davis Magnet Elementary School, 2014, 2015
- Team Leader, Physiology Understand Week (PhUn week), UMMC, 2012,2013, 2014, 2015
Teaching/Mentoring:
- Mississippi Health Sciences Mentoring Undergraduate Program
- Huong Nguyen, Mississippi State University 2014-2015
- Caleb Reese, Belhaven University 2013-2014
- Summer Undergraduate Research Experience Program
- Nick Bohannan, University of Mississippi, Summer 2015
- Olivia McNeal, Jackson State University, Summer 2014
- Ben Rudsenske, Mississippi State University, Summer 2013
Research
Funding:
- 15PRE24700010. American Heart Association. $52,000, Low Birth Weight and Women’s Cardiovascular Health. Dasinger (PI)
- Your Content Goes Here
Oral Presentations and Invited Participation in Scientific Meetings:
- Oral Presentation, Adverse Perinatal Environment and Priming of Metabolic and Cardiovascular System to Chronic Disease/ APS Conference, San Diego, CA, April 29, 2014
- Oral Presentation, The Heart of the Matter: Menopause, Sex Steroids, and Cardiovascular
- Oral Presentation, WEH Trainee Award Finalist/APS Conference, Boston, MA, March 2015
- Oral Presentation, WEH Trainee Award Finalist/ APS Conference, San Diego, CA, April 2016
- Oral Presentation, Origins of Adult Cardiovascular and Metabolic Disease, San Diego, CA, April 2016
Publications
- Dasinger JH, Davis GK, Newsome, AD, Alexander BT. Developmental Programming of Hypertension: Physiological Mechanisms. Hypertension. 2016; PMID:27550912
- Dasinger JH, Intapad S, Backstrom MA, Carter AJ, Alexander BT. Intrauterine growth restriction programs accelerated age-related increased cardiovascular risk in male offspring. Am J Physiol Renal Physiol. 2016; 311:F312-319. PMID:27147668
- Dasinger JH, Intapad S, Rudsenske BR, Davis GK, Newsome AN, Alexander BT. Chronic blockade of the androgen receptor abolishes age-dependent increases in blood pressure in female growth-restricted rats. Hypertension. 2016;67:1281-1290. PMID:27113045
- Dasinger JH, Alexander BT. Gender differences in developmental programming of cardiovascular diseases. Clin Sci (Lond). 2016;130 (Part 5), Pages: 337-348
- Intapad S, Dasinger JH, Brown AD, Fahling JM, Esters J, Alexander BT. Glucose intolerance develops prior to increased adiposity and accelerated cessation of estrous cyclicity in female growth-restricted rats. Pediatr Res. 2016; 79:962-970. PMID: 26854801
- Alexander BT, Dasinger JH, Intapad S. Fetal programming and cardiovascular pathology. Compr Physiol. 2015; 5(2):997-1025. PMID: 25880521
- Alexander BT, Dasinger JH, Intapad S. Low birth weight: Impacts on women’s health. Clin Therapeutics. 2014, pii: S0149-2918(14)00390-7. PMID: 25064626
- Intapad S, Ojeda NB, Dasinger JH, Alexander BT. Sex differences in the developmental origins of cardiovascular disease. Physiology. (Bethesda). 2014;29:122-132. PMID: 24583768
- Intapad S, Tull FL, Brown AD, Dasinger JH, Ojeda NB, Fahling JM, Alexander BT. Renal denervation abolishes the age-dependent increase in blood pressure in female intrauterine growth-restricted rats at 12 months of age. Hypertension. 2013; 61:828-34 PMID: 23423240
- Ojeda NB, Intapad S, Royals TP, Black JT, Dasinger JH, Tull FL, Alexander BT. Hypersensitivity to acute ANG II in female growth-restricted offspring is exacerbated by ovariectomy. Am J Physiol Regul Integr Comp Physiol. 2011 301:1199-205 PMID: 21832208
- 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 PMID: 20219873
Book Chapter
- Dasinger, JH, Intapad S, Alexander BT. Chapter 61, “Placental insufficiency: The impact on cardiovascular health in the mother and her offspring across the lifespan,” Book: Pathophysiology and Pharmacotherapy of Cardiovascular Disease, Editors: Jagadeesh, Balakumar, and Maung. Springer Healthcare, Adis Books, Auckland, New Zealand
Abstracts
- JH Dasinger, S Intapad, BR Rudsenske, BT Alexander. Chronic flutamide treatment alters intrarenal renin angiotensin system expression in intrauterine growth restricted female rats. The FASEB J 2016.
- Newsome AD, Dasinger JH, Intapad S, Davis GK, Alexander BT. Effect of aging on kidney function in male intrauterine growth restricted rats. The FASEB J 2016.
- JH Dasinger, S Intapad, MA Backstrom, BT Alexander. Vendor-specific effect on sex differences in the developmental programming of blood pressure in the Sprague Dawley rat. Gender Conference 2015.
- JH Dasinger, S Intapad, MA Backstrom, AJ Carter, BT Alexander. Vendor specific differences in the Sprague Dawley rat strain alter baseline blood pressure and body composition and influence the impact of slow fetal growth on later cardiovascular risk. Hypertension 2015
- JH Dasinger, S Intapad, BR Rudsenske, AJ Carter, BT Alexander. Postmenopausal hypertension is blunted following chronic flutamide treatment in intrauterine growth restricted female rat. FASEB J April 2015, 29:966.2.
- E Gillis and JH Dasinger. Teaching Physiology to Homeschool Students in Rural Mississippi. FASEB J April 2015 29:LB754.
- S Intapad, JH Dasinger, MA Backstrom, BT Alexander. Impact of Commercial Vender on the Developmental Programming of Later Chronic Health. FASEB J April 2015 29:811.20.
- JH Dasinger, S Intapad, MA Backstrom, BT Alexander. Intrauterine Growth Restriction Programs a Reduction in Nitric Oxide Bioavailability Indicative of Accelerated Vascular Aging in the Male Growth-restricted Rat. Hypertension 2014, A235.
- S Intapad, MA Backstrom, AJ Carter, JH Dasinger, BT Alexander. Chronic Endothelin Type A Receptor Blockade Abolishes Age-dependent Hypertension in Female Intrauterine Growth Restricted Rat Offspring. Hypertension 2014, A236.
- JH Dasinger, S Intapad, M Backstrom, NB Ojeda, BT Alexander. Age impacts the developmental programming of blood pressure regulation in the intrauterine growth restricted male rat. 2014 The FASEB J, 1085.10
- S Intapad, JH Dasinger, M Backstrom, BT Alexander. Blockade of the renin angiotensin system abolishes age-dependent hypertension in female intrauterine growth restricted rats in the absence of enhanced sensitivity to acute angiotensin II. 2014 The FASEB J, 1085.2.
- JH Dasinger, S Intapad, J Fahling, BT Alexander. Sex differences in adipose tissue glucose metabolism following a postnatal high fat and high sucrose diet in a model of intrauterine growth restriction. Gulf Coast Physiological Society Meeting, June 2013.
- S Intapad, AD Brown, FL Tull, JM Fahling, JH Dasinger, NB Ojeda, BT Alexander. Impaired pancreatic function contributes to the age-dependent development of metabolic syndrome in female intrauterine growth restricted rats. 2013, The FASEB J, B76 1114.8.
- S Intapad, AD Brown, JM Fahling, JH Dasinger, NB Ojeda, BT Alexander. Renal denervation abolishes age-dependent hypertension in female intrauterine growth restricted rats. 2013, The FASEB J, B133 906.17.
- S Intapad, AD Brown, FL Tull, JH Dasinger, NB Ojeda, BT Alexander. A Postnatal Diet Rich in Fat and Sucrose Leads to the Differential Alterations in Renal Function and Metabolic Health in Male Control and Intrauterine Growth Restricted Offspring. Hypertension 2012; 60:A18.
- S Intapad, FL Tull, AD Brown, JH Dasinger, NB Ojeda, BT Alexander. Intrauterine growth restriction induces a greater susceptibility to hypertension and metabolic dysfunction with aging in female growth-restricted rats. 2012 The FASEB J.
- S Intapad, FL Tull, JH Dasinger, F Fan, RJ Roman, NB Ojeda, BT Alexander. 20-HETE contributes to hypersensitivity to acute angiotensin II in intrauterine growth restricted rats. Hypertension, 2011;58:e33-e183.
- S Intapad, FL Tull, JH Dasinger, NB Ojeda, BT Alexander. Differential programming of endothelin receptor expression contributes to sex differences in adult blood pressure regulation in intrauterine growth restricted offspring. The Physiologist, 2011;4.27.
- S Intapad, FL Tull, JH Dasinger, JT Black, NB Ojeda, BT Alexander. Sex-specific mechanisms contribute to the pressor response to acute angiotensin II in a rat model of intrauterine growth restriction. 2011 The FASEB J.
- S Intapad, JM Wiseman, FL Tull, JH Dasinger, JT Black, NB Ojeda, C Maric, BT Alexander. A mismatch of fetal and postnatal nutrition leads to sex dependent differences in postnatal growth and blood glucose levels. 2011 The FASEB J.
- JH Dasinger, FL Tull, H Zhang, L Bufkin, J Martin, P Rhodes, BT Alexander, NB Ojeda. Postnatal rapid growth in low birth weight newborn is associated with increased visceral adipose tissue in adulthood. Gulf Coast Physiological Society Meeting, 2011.
- JM Johnson, JM Wiseman, FL Tull, JH Dasinger, S Intapad, NB Ojeda, BT Alexander. A Mismatch of Pre- and Post-Natal Nutrition Leads to Sex- and Age- Dependent Differences in Postnatal Growth and Blood Glucose Levels. Global Obesity Summit, Jackson, MS 2010.
- NB Ojeda, DG Romero, JH Dasinger, BT Alexander, P Rhodes. Aldosterone levels are inversely correlated to superoxide dismutase activity in the low birth weight newborn. FASEB J 2010;629.6
Louise Christine Evans, Ph.D.
Postdoctoral Fellow
Department of Physiology
Medical College of Wisconsin
8701 Watertown Plank Road
Milwaukee, WI 53226
- levans@mcw.edu
Education/Training:
- 2003-2007 MSci (First Class), Pharmacology, University of Bristol, Bristol, UK
- 2005-2006 Research Intern, Urogenital Biology, GlaxoSmithKline, King of Prussia, PA, USA
- 2007-2008 MSc (Distinction), Cardiovascular Disease, University of Edinburgh, Edinburgh, UK
- 2008-2011 Ph.D., Molecular Physiology (Renal), University of Edinburgh, Edinburgh, UK
- 2011-2012 Central Control of salt appetite. Supervisor- Dr. Matthew Bailey, University of Edinburgh, Edinburgh, UK
- 2012- Renal Physiology. Supervisor- Dr. Allen Cowley Jr., Medical College of Wisconsin, Milwaukee, USA
Professional Memberships:
- 2013- American Heart Association
- 2010- The Physiological Society
- 2016- American Physiological Society
- 2003-2007 British Pharmacology Society
Honors and Awards:
- 2016 Kidney Council New Investigator Award, American Heart Association, Hypertension Scientific Sessions, Orlando, Florida.
- 2016 Selected Co-Chair “Salt and Hypertension”, American Heart Association, Hypertension Scientific Sessions, Orlando, Florida.
- 2016 Featured in AHA Connections Summer issue, “Recognizing Excellence in Research”.
- 2016 Trainee Travel Award, SRC Renal Hemodynamics Conference, Big Sky, Montana.
- 2016 Selected Co-Chair “Advances in Renal Physiology II”, Experimental Biology, San Diego, California.
- 2016 Highest ranking abstract “Advances in Renal Physiology II”, Experimental Biology, San Diego, California.
- 2015 Excellence in Science Postdoc Award, Medical College of Wisconsin.
- 2015 Postdoctoral Research Poster Award Winner, Medical College of Wisconsin Research Day.
- 2015 Hypertension Council New Investigator Award, American Heart Association, Hypertension Scientific Sessions, Washington D.C.
- 2015 Top 10% Scoring Abstract at American Heart Association Specialty Conferences, American Heart Association, Best of AHA Specialty Conferences.
- 2015 British Heart Foundation Research Excellence International Travel Award.
- 2015 Professional Development Travel Award, Medical College of Wisconsin.
- 2014 Postdoctoral Research Poster Award Winner, Medical College of Wisconsin Research Day.
- 2013 Postdoctoral Research Poster Award Winner, Medical College of Wisconsin Research Day.
- 2013 Selected Co-Chair “Recent Advances in Renal Pathophysiology”, Experimental Biology, Boston, Massachusetts.
- 2012 First Prize in Student Poster Competition, British Heart Foundation Centre for Research Excellence Symposium, University of Edinburgh.
- 2010 Runner Up in Physiological Society Poster Competition, Main Meeting Manchester.
- 2007 Department of Pharmacology award for MSci dissertation, University of Bristol.
Service:
- 2015-2016 Spotlight on Science Committee Member, Medical College of Wisconsin, Miwaukee, WI, USA
Funding:
- 2013-2015 American Heart Association Postdoctoral Fellowship, Medical College of Wisconsin, $90,772
- 2011-2012 British Heart Foundation Fellowship Transition Award, British Heart Foundation Centre for Research Excellence, University of Edinburgh, £38,000
- 2010 University of Edinburgh Innovation Initiative Grant, British Heart Foundation Centre of Research Excellence, University of Edinburgh, £2,250
- 2007-2011 British Heart Foundation Ph.D. Studentship, British Heart Foundation Centre of Research Excellence, University of Edinburgh, £108,731
Peer Reviewed Publications:
Books
Evans LC, Cowley AW. Renal Medullary Circulation. Morgan & Claypool Life Sciences. 2015 doi: 10.4199/C00136ED2V01Y201507ISP064
Manuscripts:
Accepted
Evans LC, Ivy JR, Wyrwoll C, McNairn JA, Menzies RI, Christensen TH, Al-Dujaili EA, Kenyon CJ, Mullins JJ, Seckl JR, Holmes MC, Bailey MA. Conditional deletion of Hsd11b2 in the brain causes salt appetite and hypertension. Circulation. 2016. April 5:133(14):1360-70
Palygin O, Levchenko V, Evans LC, Blass G, Cowley AW Jr, Staruschenko A. Use of enzymatic biosensors to quantify endogenous ATP or H2O2 in the kidney. Journal of Visualized Experiments. 2015. Oct 12;(104).
Wyrwoll C, Keith M, Noble J, Stevenson PL, Bombail V, Crombie S, Evans LC, Bailey MA, Wood E, Seckl JR, Holmes MC. Fetal brain 11β-hydroxysteroid dehydrogenase type 2 selectively determines programming of adult depressive-like behaviors and cognitive function, but not anxiety behaviors in male mice. Psychoneuroendocrinology. 2015. Sep;59:59-70.
Evans LC, Ryan RP, Broadway E, Skelton MM, Kurth T, Cowley AW Jr. Null mutation of the nicotinamide adenine dinucleotide phosphate-oxidase subunit p67phox protects the Dahl-S rat from salt-induced reductions in medullary blood flow and glomerular filtration rate. Hypertension. 2015. Mar;65(3):561-8.
Cowley AW Jr., Moreno C, Jacob HJ, Peterson CB, Stingo FC, Ahn KW, Liu P, Vannucci M, Laud PW, Reddy P, Lazar J, Evans L, Yang C, Kurth T, Liang M. Characterization of biological pathways associated with a 1.37 Mbp genomic region protective of hypertension in Dahl S rats. Physiological Genomics. 2014. Jun 1;46(11):398-410.
Burnstock G, Evans LC, Bailey MA. Purinergic signaling in the kidney in health and disease. Purinergic Signaling. 2014. Mar;10(1)71-101.
Craigie E, Evans LC, Mullins JJ, Bailey MA. Failure to downregulate the epithelial sodium channel causes salt sensitivity in Hsd11b2 heterozygote mice. Hypertension. 2012. Sep;60(3):684-90.
Evans LC, Livingstone DE, Kenyon CJ, Jansen MA, Dear JW, Mullins JJ, Bailey MA. A urine-concentrating defect in 11beta-hydroxysteroid dehydrogenase type 2 null mice. Am J Physiol Renal Physiol. 2012. Aug 15;303(4):F494-502.
Dunbar DR, Khaled H, Evans LC, Al-Dujaili EA, Mullins LJ, Mullins JJ, Kenyon CJ, Bailey MA. Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney. Physiol Genomics. 2010. Feb 4;40(3):158-66.
Thorneloe KS, Sulpizio AC, Lin X, Figueroa DJ, Clouse AK, McCafferty GP, Chendrimada TP, Lashinger ES, Gordon E, Evans L, Misajet BA, Demarini DJ, Nation JH, Casillas LN, Marquis RW, Votta BJ, Sheardown SA, Xu X, Brooks DP, Laping NJ, Westfall TD. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part 1. J Pharmacol Exp Ther. 2008. Aug;326(2):432-42
In Review
Evans LC, Petrova G, Kurth T, Bukowy JD, Mattson DL, Cowley AW Jr. Increased renal perfusion pressure drives renal immune cell infiltration in the Dahl salt-sensitive rat. Hypertension; HYPE201709208
Palygin O*, Evans LC*, Cowley AW Jr., Staruschenko A. Increased renal perfusion pressure causes cortical ATP release in anesthetized Sprague Dawley rats. *Authors contributed equally. Circulation Research: CIRCRES/2017/310926
In Preparation
Evans LC*, Dayton A*, Yang C, Liu P, Kurth T, Woo Ahn K, Komas, S, Stingo FC, Laud PW, Vannucci M, Liang M, Cowley AW Jr. Transcriptomic Analysis reveals pathways regulated by renal perfusion pressure independently of dietary salt in the Dahl-S rat. *Authors contributed equally.
Invited Lectures and Presentations:
2017 “The role of NADPH oxidase subunit p67phox in the regulation of renal function in Dahl S rats”, Invited symposium presentation, Experimental Biology, Chicago, Illinois.
2016 “Reversal of hypertension stops, but does not reverse, renal T-cell infiltration in the Dahl salt-sensitive rat”, American Heart Association Hypertension, Scientific Sessions, Orlando, Florida.
2016 “Increased renal perfusion pressure (rpp) augments renal immune cell infiltration in Dahl salt-sensitive (SS) rats”, FASEB Renal Hemodynamics and Cardiovascular Function in Health and Disease, Big Sky, Montana.
2016 “The role of NADPH oxidase subunit p67phox in the regulation of renal blood flow in Dahl S (SS) rats”, Experimental Biology, San Diego, California.
2015 “Increased blood pressure drives renal T-cell infiltration in the Dahl salt-sensitive rat”, American Heart Association Hypertension Scientific Sessions, Washington DC.
2015 “Oxidative stress in the initiation and progression of salt-sensitive hypertension”, Invited seminar, University of Edinburgh/BHF Centre for Cardiovascular Science, Edinburgh.
2015 “The initiation and progression of salt-sensitive hypertension”, Milwaukee’s American Heart Association Integration Meeting, Milwaukee, Wisconsin.
2013 “Evaluation of the role of NAD(P)H oxidase subunit p67phox in the regulation of medullary blood flow in Dahl S rats”, Experimental Biology, Boston, Massachusetts.
2013 “Targeting of 11βHSD2 in the NTS links salt appetite and hypertension”, Experimental Biology, Boston, Massachusetts.
2011 “Role of 11βHSD2 in the regulation of sodium and water homeostasis”, Invited seminar, Epithelial Systems Biology Lab, NIH, Bethesda, Maryland.
2011 “Evaluation of water turnover and urine concentration in 11β hydroxysteroid dehydrogenase type 2 knockout (11βHSD2-/-) mice”, Experimental Biology, Washington DC.
Mentoring:
Mentoring:
MCW Summer Program for Undergraduate Research
2013 Al Haji Camara, Marquette University
2014 Elizabeth Broadway, University of Wisconsin-Stevens Point.
Xiaoqing Pan
Department of Physiology & Cancer Center
Medical College of Wisconsin
Milwaukee, WI 53226
- xpan@mcw.edu
Education/Training:
- 2014.12 — present Postdoctoral research fellow, Department of Physiology & Cancer Center Medical College of Wisconsin
- 2013.6 — 2016.6 Postdoctoral research fellow, Department of Statistics and Finance University of Science and Technology of China
- 2008.9 — 2013.6 Junior Lecturer and Research Assistant, Department of Statistics and Finance University of Science and Technology of China
- 2008.9 — 2013.6 Ph.D in Probability and Statistics, Department of Statistics and Finance University of Science and Technology of China
- 2004.9 — 2008.6 Bachelor in Statistics, School of Mathematics and Computer Science Nanjing Normal University
Awards and Honors:
- 2013 Chinese Academy of Science Deans Award
- 2013 National Scholarship, Ministry of Education of the People’s Republic of China
- 2012 “Zhu Li Yue Hua” Excellent Ph.D Student Scholarship, Chinese Academy of Science
Services:
- Referee for — Journal of Korean Statistical Society — Probability in the Engineering and Informational Science — Statistics & Probability Letters
- Since 2016 Statistical consultant and data analyst at Medical College of Wisconsin — for American Heart Association grant members — for members at Department of Physiology and Cancer Center
- Services at Department of Statistics and Finance at University of Science and Technology of China — Academic advisor of 8 undergraduate students 2013 – 2016 — Social Committee, Colloquium Committee 2013 – 2016 — Oral Defense Committee 2016
Funding:
- 2015.1.1 — 2017.12.31 The National Natural Science Foundation of China Project: Tail Dependent Structures of Extreme Risks Funding Agency: The National Natural Science Foundation of China Role: Principal Investigator
- 2014.9.1 — 2016.6.30 The 56th Postdoctoral Science Foundation in China Project: Identifying and Comparison of Extreme risks Funding Agency: Ministry of Personnel of the People’s Republic of China Role: Principal Investigator
- 2014.1.1 — 2015.12.31 The Fundamental Research Funds for the Central Universities Project: Hidden Regular Variation with Applications to Risk Management Funding Agency: Ministry of Education of the People’s Republic of China Role: Principal Investigator
Publications:
Pan X., Qiu G. and Hu T. (2016). Stochastic orderings for elliptical random vectors. Journal of Multivariate Analysis, 148, 83-88.
Ju S. and Pan X1. (2016). A new proof for the peakedness of linear combinations of random variables. Statistics and Probability Letters, 114, 93-98.
Yuan M., Pan X. and Yang Y. (2015). Bayes factors based on robust TDT-type tests for family trio design. Statistical Applications in Genetics and Molecular Biology, 14(3), 253-264.
Pan X1. , Yuan M. and Kochar S C. (2015). Stochastic comparisons of weighted sums of arrangement increasing random variables. Statistics and Probability Letters, 102, 42-50.
Pan X., Xu M. and Hu T. (2013). Some inequalities of linear combinations of independent random variables: II. Bernoulli, 19(5A), 1776-1789.
Pan X., Leng X. and Hu T. (2013). The second-order version of Karamata’s theorem with applications. Statistics and Probability Letters, 83, 1397-1403.
Mao T., Pan X. and Hu T. (2013). On orderings between weighted sums of random variables. Probability in the Engineering and Informational Science, 27(1), 85-97.
Lv W., Pan X. and Hu T. (2013). Asymptotics of the risk concentration based on the tail distortion risk measure. Statistics and Probability Letters, 83, 2703-2710.
Chen D., Mao T., Pan X. and Hu T. (2012). Extreme value behavior of aggregate dependent risks. Insurance: Mathematics and Economics, 50(1), 99-108.
Submitted Papers:
Pan X. and Li X. (2017) Increasing convex order on generalized aggregations of stochastically arrangement increasing random variables with applications. Journal of Applied Probability, accepted.
Pan X. and Li X. (2016) On capital allocation for stochastic arrangement increasing actuarial risks. Dependence Modelling, submitted.
Baker M.A., Davis J.S., Liu P, Pan X., Iczkowski A.K., Gallagher T. S., Bishop K., Regner R.K., Liu Y., Liang M. (2016) Tissue-specific microRNA expression patterns in four types of kidney disease. Journal of the American Society of Nephrology, submitted.
Working Manuscripts:
Pan-cancer pathway and network analysis of RNASEQ data across cancers (With Yifan Yang, Xing Hua and Pengyuan Liu)
SEPAR: a powerful tool for identifying disease-associated alternative polyadenylation from RNASEQ data. (with Yifan Yang and Pengyuan Liu)
Urinary metabolites associated with blood pressure on low-or high sodium intakes. (with Mingyu Liang et al.)
Working Statistical Software:
R package: SEPAR. (with Yifan Yang and Pengyuan Liu)
Selected Presentations:
November 2016 Department of Mathematical Sciences at Northern Illinois University, USA. Invited talk: Stochastic Comparison of Elliptical Random Vectors with Applications
June 2016 International Workshop on Mathematical Reliability and Safety, Xuzhou, China
Invited talk: Stochastic Orderings for Elliptical Random Vectors
September 2015 Department of Mathematics at Illinois State University, USA. Invited talk: A review of stochastic comparison for linear combinations of random variables
July 2013 8th Conference on Extreme Value Analysis, Shanghai, China
Invited talk: The Second-order Version of Karamata’s Theorem With Applications
July 2012 International conference on Quantitative Finance and Risk Management, China
Contributed talk: Asymptotic Behavior of Tail Distortion Risk Measure For Extreme Risks
March 2012 International conference on Actuarial and Financial Mathematics, China
Contributed talk: Asymptotic Behavior of Tail Distortion Risk Measure For Extreme Risks
June 2011 International Workshop on Stochastic Orders in Reliability and Risk Management, Ximen, China. Contributed talk: Some Inequalities of Linear Combinations of Independent Random Variables
Teaching Experience:
Teaching at University of Science and Technology of China
Fall 2014 Probability and Statistics, undergraduate course, two classes, totally 240 students, for non-majors
Fall 2011 Seminar “Modelling Extremal Events: for Insurance and Finance” graduate course, 12 students, 8 weeks, for majors
Spring 2011 Seminar “Quantitative Risk Management” graduate course, 12 students, 8 weeks, for majors
Fall 2010 Seminar “Extreme value theory: An Introduction” graduate course, 14 students, 6 weeks, for majors
Teaching assistant at University of Science and Technology of China
Fall 2008, 2009, 2012; Spring 2010, 2012, 2013 Probability and Statistics undergraduate course, for non-majors
Spring 2009 Mathematical Statistics undergraduate course, for majors
Fall 2011, 2012 Probability Theory
Spring 2011 Stochastic Process undergraduate course, for majors