Faculty Profile: Ulrike Mende, MD, FAHA

Ulrike Mende
Ulrike Mende, MD, FAHA
Associate Professor of Medicine
Medicine
Work: +1 401-444-9854
Ulrike Mende is interested in the functional role of G proteins (GTP-binding proteins), which transmit signals from the cell surface to the inside, and their regulators (Regulators of G protein Signaling) in the heart. Changes in their amount or function often lead to compromised cardiac function and disease, such as cardiac hypertrophy, failure and arrhythmias. Our goal is to delineate the underlying molecular mechanisms in both myocytes and fibroblasts and devise new therapeutic strategies.

Biography

Dr. Mende attended Medical School at the University of Hamburg in Germany, followed by 7 years postdoctoral training in the Department of Pharmacology at the University of Hamburg and in the Cardiovascular Division of Brigham and Women's Hospital and Harvard Medical School. She launched a career as an independent scientist and principal investigator at Brigham and Women's Hospital and was promoted at Harvard Medical School to Instructor in 1995 and to Assistant Professor of Medicine in 2000. In 2005, Dr. Mende was recruited by Rhode Island Hospital and Brown Medical School as an Associate Professor of Medicine to help establish a new Cardiovascular Research Center. Her research focuses on cell signaling in heart cells under normal and pathophysiological conditions. Her work has been funded by the American Heart Association (AHA) and the National Institutes of Health (NIH), where she has also been serving as grant reviewer for many years.

Research Description

Dr. Mende has a background in pharmacology and molecular cardiology and a particular research interest in the regulation of heart rate, contractile function and extracellular matrix production via G protein-mediated signaling pathways in the healthy and diseased heart. Signal transduction via heterotrimeric G proteins is one of the most important mechanisms of signal transfer across the cell membrane in virtually all cells, including cardiac cells. G proteins act as relay switches that link extracellular signals on the cell surface to changes in ion channel activity and second messenger pathways inside the cell, which in turn elicit changes in cellular function. Dr. Mende's research focuses on elucidating how perturbations in G proteins and their regulators (so-called RGS proteins or Regulators of G protein Signaling) in cardiac myocytes and fibroblasts contribute to the development of cardiac hypertrophy and fibrosis, heart failure and arrhythmias, with the long-term goal to identify potential new therapeutic targets. Her team conducts gain- and loss-of-function studies in primary heart cell cultures and genetically modified mouse models and uses molecular and biochemical assays to examine gene/protein expression and regulation as well as physiological techniques to assess heart cell and cardiac functions. Current projects in the Mende laboratory include investigations of (i) the regulation of G protein signaling in cardiac fibroblasts and their role in determining the cardiac remodeling response to hemodynamic stress, and (ii) the functional significance and mechanisms of communication between cardiac fibroblasts and myocytes. It is well recognized that the two major cardiac cell types determine the structural, mechanical and electrical characteristics of the heart, but the communication between them is still poorly understood. To that end, the Mende laboratory (in collaboration with other Brown faculty) has been developing novel 2D and 3D co-culture models that mimic key characteristics of cardiac tissue and allow for examination of myocyte-fibroblast communication under defined experimental conditions.

Grants and Awards

Honorary M.A. ad eundum (Brown University), 2007

Fellow of the American Heart Association (FAHA, American Heart Association), 2006

9th Annual AstraZeneca Cardiovascular Young Investigators' Forum, 2nd Prize (AstraZeneca), 2003

New Investigator Travel Award (American Heart Association), 2002

New England Cardiovascular Research Competition, 3rd Prize (AstraZeneca), 1998

Louis N. and Arnold M. Katz Basic Science Research Prize for Young Investigators, Finalist (American Heart Association), 1998

Thomas W. Smith Fellowship Award (Brigham and Women's Hospital, Boston), 1998-1999

Postdoctoral Fellowship Award (Deutsche Forschungsgemeinschaft), 1992-1994

Dr. Martini Award (University of Hamburg, Germany), 1991

Affiliations

International Society for Heart Research (since 2003)
Heart Failure Society of America (2003-2004)
American Society for Biochemistry and Molecular Biology (1996-2011)
American Heart Association (since 1995)
German Society of Heart and Circulation Research (since 1991)
German Society of Pharmacology and Toxicology (1990-2000)
American Physiological Society (since 2012)

Funded Research

Current Research Funding:

Title: Advancing Experimental Models top Study Intercellular Communication of Cardiac Cells
Grant/Source: R21 HL113918-01A1; NIH/NHLBI
Dates: 01/16/2013 – 12/31/2014
Amount: $137,500 per year (direct)
Role: Principal Investigator

Title: Regulation of Gq Signaling in Cardiac Fibroblasts and its Role in Cardiac Remodeling
Grant/Source: R01 HL114784-01A1; NIH/NHLBI
Dates: 09/01/2013 – 05/31/2017
Amount: $303,031 per year (direct)
Role: Principal Investigator

Title: A Multi-Scale Approach to Cardiac Arrhythmia: from the Molecule to the Organ
Source: R01 HL110791-01A1; NHLBI
Dates: 08/01/2013 – 05/31/2018
Amount: Partial salary support
Role: Co-Investigator (PI: Dr. G. Koren)

Title: Endothelial Injury and Repair: CardioPulmonary Vascular Biology COBRE
Source: P20 GM103652-01A1; NIH/NIGMS
Dates: 09/20/2013 – 05/31/2018
Amount: Partial salary support
Role: Faculty Mentor (PI: Dr. S. Round; Project PI: Dr. P. Zhang)

Teaching Experience

My academic teaching portfolio includes the entire spectrum of Basic and Clinical Pharmacology and Toxicology for medical students that I taught in the traditional lecture format in Germany from 1988 to 1992. In 1993, I had the opportunity to gain experience with the problem-oriented learning approach at Harvard Medical School by leading a tutorial group in the Principles in Pharmacology course for 1st year medical students. From 2001-2005, I was on the faculty for the Integrated Human Physiology course as tutor and was nominated by Harvard Medical School students for teaching awards in 2002 and 2004. Since I joined the faculty of Brown University, I am involved in teaching undergraduate, graduate and medical students through the courses listed below.
In addition, and on a more continuous basis, I have been teaching postdoctoral fellows, students and technical research assistants in my laboratory by guiding them in their research and serving as their mentor. I am also a readily available resource for other Principal Investigators and members of their laboratories.

Courses Taught

  • Directed Research/Independent Study (Biol 1950/1960)
  • Integrated Medical Sciences III - Cardiovascular (BIOL 3660)
  • Receptor, Channels and Signaling (BIOL 2170)

Selected Publications

  • Zhang P, Mende U. Functional role, mechanisms of regulation, and therapeutic potential of regulator of G protein signaling 2 in the heart. Trends Cardiovasc Med. 2013 Aug 17 [Epub ahead of print] (2013)
  • Park-Windhol C, Zhang P, Zhu M, Su J, Chaves Jr L, Maldonado AE, King ME, Rickey L, Cullen D , Mende U. Gq/11-mediated signaling and hypertrophy in mice with cardiac-specific transgenic RGS2 expression. PLoS ONE 2012; 7: e40048. (2012)
  • Mackiewicz U, Czarnowska E, Brudek M, Pająk B, Duda M, Emanuel K, Csanyi G, Fedorowicz A, Grochal E, Tyrankiewicz U, Skórka T, Mende U, Lewartowski B, Chłopicki S. Preserved cardiomyocyte function and altered desmin pattern in transgenic mouse model of dilated cardiomyopathy. J Mol Cell Cardiol 2012; 52(5): 978-987. (2012)
  • Desroches BR, Zhang P, Choi B, King ME, Maldonado AE, Li W, Rago A, Liu GX, Nath N, Hartmann KM, Yang B, Koren G, Morgan JR, Mende U. Functional scaffold-free 3D cardiac microtissues: a novel model for the investigation of heart cells. Am J Physiol Heart Circ Physiol 2012; 302(10): H2031-H2042. (2012)
  • Zhang P, Su J, Mende U. Cross talk between cardiac myocytes and fibroblasts: from multiscale investigative approaches to mechanisms and functional consequences. Am J Physiol Heart Circ Physiol 2012; 303(12): H1385-H1396 (2012)
  • Hirose M, Takeishi Y, Nakada T, Shimojo H, Kashihara T, Suzuki S, Mende U, Matsumoto K, Yamada M. Nicorandil prevents Gaq-induced progressive heart failure and ventricular arrhythmias in transgenic mice. PLoS ONE 2012; 7(12): e52667 (2012)
  • Zhang P, Mende U. Regulators of G Protein Signaling in the heart and their potential as therapeutic targets. Circ Res 2011; 109: 320-333. (2011)
  • Pinz I, Zhu M, Mende U, Ingwall J. An improved isolation procedure for adult mouse cardiomyocytes. Cell Biochem Biophys 2011; 61: 93-101. (2011)
  • Chakir K, Zhu W, Tsang S, Woo AY, Yang D, Wang X, Zeng X, Rhee MH, Mende U, Koitabashi N, Takimoto E, Blumer KJ, Lakatta EG, Kass DA, Xiao RP. RGS2 is a primary terminator of β2-adrenergic receptor-mediated Gi signaling. J Mol Cell Cardiol 2011; 50(6): 1000-1007. (2011)
  • Hirose M, Takeishi Y, Niizeki T, Nakada T, Shimojo H, Kubota I, Mende U, Yamada M. Diacylglyerol kinase z inhibits ventricular tachyarrythmias in a mouse model of heart failure: Roles of canonical transient receptor potential (TRPC) channels. Circ J 2011; 75:2333-2342. (2011)
  • Zhang P, Su J, King ME, Maldonado Lopez AE, Park C, Mende U. Regulator of G protein signaling 2 is a functionally important negative regulator of Angiotensin II-induced cardiac fibroblast responses. Am J Physiol Heart Circ Physiol 2011; 301: H147-H156. (2011)
  • Hirose M, Takeishi Y, Niizeki T, Shimojo H, Nakada T, Kubota I,Nakayama J, Mende U, Yamada M. Diacylglyerol Kinase z inhibits Gaq-induced atrial remodeling in transgenic mice. Heart Rhythm 2009; 6: 78-84. (2009)
  • Niizeki T, Takeishi Y, Kitahara T, Arimoto T, Koyama Y, Goto K, Mende U, Kubota I. Diacylglyerol Kinase z rescues Gaq-induced heart failure in transgenic mice. Circ J 2008; 72: 309-317. (2008)
  • Drelicharz L, Kozlovski V, Skorka T, Heinze-Paluchowska S, Jasinski A, Gebska A, Guzik T, Olszanecki R, Wojnar L, Mende U, Csanyi G, Chlopicki S. NO and PGI2 in coronary endothelial dysfunction in transgenic mice with dilated cardiomyopathy. Basic Res Cardiol 2008; 103: 417-430. (2008)
  • Zhu M, Gach A, Liu GX, Xu X, Lim CC, Zhang JX, Mao L, Chuprun K, Koch WJ, Liao R, Koren G, Blaxall BC, Mende U. Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active Gao protein. Am J Physiol Heart Circ Physiol 2008; 294: H1335-H1347. (2008)
  • Fish S, Gray S, Heymans S, Wang B, Haldar S, Pfister O, Cui L, Kumar A, Lin Z, Sen-Banerjee S, Das H, Petersen CA, Mende U, Burleigh BA, Zhu Y, Pinto Y, Liao R, Jain M. Kruppel-like factor KLF 15 is a novel regulator of cardiomyocyte hypertrophy. Proc Natl Acad Sci USA. 2007; 104(17): 7074-7079. (2007)
  • Schmitt JP, Debold EP, Ahmad F, Armstrong A, Frederico A, Conner DA, Mende U, Lohse MJ, Warshaw D, Seidman CE, Seidman JG. Cardiac myosin missense mutations cause dilated cardiomyopathy in mouse models and depress molecular motor function. Proc Natl Acad Sci USA. 2006; 103(39): 14525-14530. (2006)
  • Zhang W, Anger T, Su J, Hao J, Xu X, Zhu M, Gach A, Cui L, Liao R, Mende U. Selective loss of fine-tuning of Gq/11 signaling by RGS2 protein exacerbates cardiomyocyte hypertrophy. J Biol Chem. 2006; 281(9): 5811-5820. (2006)
  • Hao J, Zhang W, Michalek C, Zhu M, Xu X, Mende U. Regulation of cardiomyocyte signaling by RGS proteins: differential selectivity towards G proteins and susceptibility to regulation. J Mol Cell Cardiol. 2006; 41: 51-61. (2006)
  • Anger T, Zhang W, Mende U. Differential contribution of GTPase activation and effector antagonism to the inhibitory effect of RGS proteins on Gq-mediated signaling in vivo. J Biol Chem. 2004; 279(6): 3906-3915. (2004)
  • Carvalho-Bianco SD, Kim BW, Zhang JX, Harney JW, Ribeiro RS, Gereben B, Bianco AC, Mende U, Larsen PR. Chronic cardiac-specific thyrotoxicosis increases myocardial b-adrenergic responsiveness. Mol Endocrinol. 2004; 18(7): 1840-1849. (2004)
  • Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, Kranias EG, MacLennan DH, Seidman JG, Seidman CE. Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science. 2003; 299(5611): 1410-1413. (2003)
  • Semsarian C, Ahmad I, Giewat M, Georgakopoulos D, Schmitt JP, McConnell BK, Reiken S, Mende U, Marks AR, Kass DA, Seidman CE, Seidman JG. The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model. J Clin Invest. 2002; 109(8): 1013-1020 (2002)
  • Gehrmann J, Meister M, Maguire CT, Martins DC, Hammer PE, Neer EJ, Berul CI, Mende U. Impaired parasympathetic heart rate control in mice with a reduction of functional G protein bg subunits. Am J Physiol Heart Circ Physiol. 2002; 282(2): H445-H456. (2002)
  • Mende U, Semsarian C, Martins DC, Kagen A, Duffy C, Schoen FJ, Neer EJ. Dilated cardiomyopathy in two transgenic mouse lines expressing activated G protein aq: lack of correlation between phospholipase C activation and the phenotype. J Mol Cell Cardiol. 2001; 33(8): 1477-1491. (2001)