Jeffrey Robbins

Cincinnati Children's Hospital Medical Center

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

James Gulick

Cincinnati Children's Hospital Medical Center

Hanna Osińska

Cincinnati Children's Hospital Medical Center

Jeffery D. Molkentin

Cincinnati Children's Hospital Medical Center

Raisa Klevitsky

Cincinnati Children's Hospital Medical Center

John N. Lorenz

University of Cincinnati Medical Center

Atsushi Sanbe

Iwate Medical University

Jeanne James

Medical College of Wisconsin

Timothy E. Hewett

Marshall University

David M. Warshaw

University of Vermont

Sakthivel Sadayappan

University of Cincinnati

Cooperative Institutions

University of Michigan–Ann Arbor

264

Harvard University

236

Cincinnati Children's Hospital Medical Center

220

Inserm

216

University of Cincinnati

183

Centre National de la Recherche Scientifique

176

University of Cincinnati Medical Center

160

Washtenaw Community College

155

National Institutes of Health

145

UiT The Arctic University of Norway

138

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Measurement of intraventricular pressure and cardiac performance in the intact closed-chest anesthetized mouse

AJP Heart and Circulatory Physiology (1997)

John N. Lorenz Jeffrey Robbins

To fully utilize the potential of newly developed mouse models with specific genetic mutations, it is necessary to study the functional consequences of genetic manipulation in the fully intact animal. To this end, the purpose of the present study was to develop and validate a methodology for the study of myocardial performance in the fully intact, closed-chest mouse. Left ventricular function was evaluated in euthyroid, hypothyroid, and hyperthyroid mice, animals with well-documented alterations in myocardial function. The mice were anesthetized and instrumented with polyethylene catheters in the right femoral artery and vein and with a Millar MIKRO-TIP transducer in the left ventricle via the right carotid artery. Structural and functional evidence suggested that the instrumentation procedure did not cause myocardial damage, valvular insufficiency, or aortic obstruction. Isovolumic indexes of myocardial contractility derived from the left ventricular pressure pulse and its first derivative demonstrated a 40% increase in contractility in the hyperthyroid animals and a 40% decrease in contractility in the hypothyroid animals. Similar differences in the indexes of relaxation were observed. Furthermore, isoproterenol dose-response relationships of these contractile parameters were blunted in the hypothyroid animals and augmented in the hyperthyroid animals compared with euthyroid control animals. Given the small size of the mouse and the high frequency of the cardiac cycle, these data demonstrate the feasibilty of combining a high-fidelity, microtip manometer with a high-speed data-acquisition system to obtain faithful recordings of cardiac performance in the fully intact mouse.

Contractility

Ventricular pressure

Dobutamine

Cardiac cycle

10.1152/ajpheart.1997.272.3.h1137

Cite

Citations (110)

Mediating ERK1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome

Journal of Clinical Investigation (2007)

Tomoki Nakamura Melissa C. Colbert Maike Krenz Jeffery D. Molkentin Harvey S. Hahn

Noonan syndrome (NS) is an autosomal dominant disorder characterized by a wide spectrum of defects, which most frequently include proportionate short stature, craniofacial anomalies, and congenital heart disease (CHD). NS is the most common nonchromosomal cause of CHD, and 80%-90% of NS patients have cardiac involvement. Mutations within the protein tyrosine phosphatase Src homology region 2, phosphatase 2 (SHP2) are responsible for approximately 50% of the cases of NS with cardiac involvement. To understand the developmental stage- and cell type-specific consequences of the NS SHP2 gain-of-function mutation, Q79R, we generated transgenic mice in which the mutated protein was expressed during gestation or following birth in cardiomyocytes. Q79R SHP2 embryonic hearts showed altered cardiomyocyte cell cycling, ventricular noncompaction, and ventricular septal defects, while, in the postnatal cardiomyocyte, Q79R SHP2 expression was completely benign. Fetal expression of Q79R led to the specific activation of the ERK1/2 pathway, and breeding of the Q79R transgenics into ERK1/2-null backgrounds confirmed the pathway's necessity and sufficiency in mediating mutant SHP2's effects. Our data establish the developmental stage-specific effects of Q79R cardiac expression in NS; show that ablation of subsequent ERK1/2 activation prevents the development of cardiac abnormalities; and suggest that ERK1/2 modulation could have important implications for developing therapeutic strategies in CHD.

Noonan Syndrome

PTPN11

10.1172/jci30756

Cite

Citations (114)

Abstract 16610: High Fat Diet-induced Obesity Is Associated With Increased Ischemia Susceptibility Due To Deregulated Activation Of The Rheb/mTORC1 Pathway And Inhibition Of Autophagy

Circulation (2011)

Sebastiano Sciarretta Peiyong Zhai Dan Shao Yasuhiro Maejima Jeffrey Robbins

Sebastiano Sciarretta, 2011 Finalist and Presenting Author

RHEB

10.1161/circ.124.suppl_21.a543

Cite

Citations (0)

Overexpressed Cardiac Gs alpha Protects Against Myocardial Ischemic Injury in Conscious Rabbits

The FASEB Journal (2008)

Li Chen Xin Zhao Heather Reinhardt Ricardo J. Gelpi Jeffrey Robbins

Overexpression of cardiac Gs alpha increases cardiac rate and contractility and responsiveness to catecholamines. All of these factors should have adverse effects on the response to myocardial ischemia. We examined the effects of 30 min coronary artery occlusion (CAO) and 4 days reperfusion in transgenic (Tg) rabbits with 3–5 fold overexpressed cardiac Gs alpha (beta-MHC promotor), instrumented with a left anterior descending coronary occluder and a pressure gauge in the left ventricle along with ultrasonic segment length crystals. Infarct size (IF) was assessed histologically and with TTC. In conscious Tg rabbits compared with wild type (WT), heart rate was elevated, p<0.05, (247±10 vs. 207±10 bpm) as was left ventricular dP/dt (5600±413 vs. 3933±161 mmHg/sec). CAO was confirmed by absence of blood flow transmurally and systolic segment length shortening. Surprisingly, the Tg rabbits exhibited marked cardioprotection, where IF/area at risk was 3±1% compared to 50±3 % in WT. Proteins known to induce ischemic preconditioning, e.g., the adenosine receptor A2b and Gsk-3 beta were upregulated in Tg rabbits. Thus, the rabbit with overexpressed cardiac Gs alpha, despite elevated levels of heart rate and myocardial contractility, exhibit powerful ischemic preconditioning.

Cardioprotection

Contractility

Ischemic Preconditioning

10.1096/fasebj.22.2_supplement.51

Cite

Citations (3)

Noonan syndrome is associated with enhanced pERK activity, the repression of which can prevent craniofacial malformations

Proceedings of the National Academy of Sciences (2009)

Tomoki Nakamura James Gulick Ronald Pratt Jeffrey Robbins

A gain of function mutation in SHP2, a protein phosphatase encoded by PTPN11 , causes Noonan syndrome (NS), which is characterized in part by developmental deficits in both the cardiac and skull fields. Previously, we found that expression of the mutated protein SHP2 Q79R in the heart led to a phenotypic presentation that mimicked some aspects of NS and that this was dependent upon activation of the ERK1/2 pathway. To understand the role that ERK1/2 signaling plays in skull development through signaling in the neural crest, we explored the consequences of Q79R expression in neural crest cells, which contribute to a subset of the bony and cartilaginous structures of the skull. Hyperactivation of ERK1/2 led to craniofacial defects that included smaller skull lengths, greater inner canthal distances, and taller frontal bone heights. In proportion to the smaller skull length, mandibular bone length was also reduced. Inhibition of ERK1/2 hyperactivity as a result of Q79R expression was achieved by injection of the MAPK/ERK kinase inhibitor U0126 during pregnancy. The drug effectively decreased the severity of the craniofacial defects and restored normal skull shape and fontanelle closure. X-ray computer-assisted microtomography analysis of the head confirmed that decreasing ERK1/2 activity led to an abrogation of the craniofacial deficits and brain shape changes that presented in the mice. These data show that normal ERK1/2 signaling in the neural crest is imperative for normal craniofacial development and offer insight into how the heart and craniofacial developmental fields might be affected in some congenital syndromic presentations.

Noonan Syndrome

10.1073/pnas.0903302106

Cite

Citations (88)

Cardiac myosin binding protein-C phosphorylation accelerates β-cardiac myosin detachment rate in mouse myocardium

AJP Heart and Circulatory Physiology (2021)

Bertrand C.W. Tanner Michael J. Previs Yuan Wang Jeffrey Robbins Bradley M. Palmer

Length perturbation analysis was used to demonstrate that β-cardiac myosin characteristic rates of detachment and recruitment in the intact myofilament lattice are accelerated by Pi, phosphorylation of cMyBP-C, and the absence of cMyBP-C. The results suggest that cMyBP-C normally slows myosin detachment, including Pi-dependent detachment, and that this inhibition is released with phosphorylation or absence of cMyBP-C.

CrossBridge

Cardiac muscle

10.1152/ajpheart.00673.2020

Cite

Citations (8)

Lower extremity amputations: basis and outcome, a review of the literature.

PubMed (1993)

Alan J. Snyder Jeffrey Robbins

Artificial limbs

Source

Cite

Citations (5)

The N terminus of myosin-binding protein C extends toward actin filaments in intact cardiac muscle

The Journal of General Physiology (2021)

Sheema Rahmanseresht Kyoung Hwan Lee Thomas S. O’Leary James W. McNamara Sakthivel Sadayappan

Myosin and actin filaments are highly organized within muscle sarcomeres. Myosin-binding protein C (MyBP-C) is a flexible, rod-like protein located within the C-zone of the sarcomere. The C-terminal domain of MyBP-C is tethered to the myosin filament backbone, and the N-terminal domains are postulated to interact with actin and/or the myosin head to modulate filament sliding. To define where the N-terminal domains of MyBP-C are localized in the sarcomere of active and relaxed mouse myocardium, the relative positions of the N terminus of MyBP-C and actin were imaged in fixed muscle samples using super-resolution fluorescence microscopy. The resolution of the imaging was enhanced by particle averaging. The images demonstrate that the position of the N terminus of MyBP-C is biased toward the actin filaments in both active and relaxed muscle preparations. Comparison of the experimental images with images generated in silico, accounting for known binding partner interactions, suggests that the N-terminal domains of MyBP-C may bind to actin and possibly the myosin head but only when the myosin head is in the proximity of an actin filament. These physiologically relevant images help define the molecular mechanism by which the N-terminal domains of MyBP-C may search for, and capture, molecular binding partners to tune cardiac contractility.

Myofilament

10.1085/jgp.202012726

Cite

Citations (39)

Regulation of cardiac gene expression during development

Cardiovascular Research (1996)

Jeffrey Robbins

In the last five years, significant new insights have been made into the mechanistic bases that underlie controlled gene expression in the developing heart. Because different phenomena at a number of levels need to be understood before the process can be defined fully, these insights stem from a body of studies that have been carried out in both non mammalian and mammalian systems. These include: (1) the molecular basis for positional information in the temporal path of gestation; (2) determination of the mesoderm via the combination of positional information and inductive influences; (3) restriction of a mesoderm subset to the cardiac muscle cell lineage; and (4) the activation of those genes which encode the proteins whose functions are responsible for the heart’s action as a pump. The ultimate control for each of these processes rests upon the genomic apparatus and its timed response to a variety of internal and external influences. Although each facet of determination/differentiation depends upon both unique and overlapping genetic complements, a genera1 regulatory paradigm holds for all of these processes: diffusible factors act in fruns with specific sequences on the DNA (gene) to regulate transcription. The factors bind to short recognition sites either within or adjacent (in cis) to the gene and it is these cis-fruns interactions that control transcription. This review’s purpose is to outline what is known about these processes as they apply to the genes that are expressed in the heart during development and differentiation, from the establishment of positional value to the production of the proteins characteristic of the terminally differentiated state. Cardiac organogenesis occurs early in mammalian development. In the human, the cardiac primordium is appar

10.1016/s0008-6363(95)00081-x

Cite

Citations (22)

Anin vivo analysis of transcriptional elements in the mouse α-myosin heavy chain gene promoter

Transgenic Research (1995)

Hansjörg Rindt Arun Subramaniam Jeffrey Robbins

Transcription

10.1007/bf01973758

Cite

Citations (42)