Evren U. Azeloglu

Bio: Evren U. Azeloglu is an academic researcher from Icahn School of Medicine at Mount Sinai. The author has contributed to research in topics: Podocyte & Medicine. The author has an hindex of 26, co-authored 75 publications receiving 2340 citations. Previous affiliations of Evren U. Azeloglu include Columbia University & Mount Sinai St. Luke's and Mount Sinai Roosevelt.

The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations

Abstract: The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability.

Mechanical heterogeneity of the rat hippocampus measured by atomic force microscope indentation.

Abstract: Knowledge of brain tissue mechanical properties may be critical for formulating hypotheses about traumatic brain injury (TBI) mechanisms and for accurate TBI simulations. To determine the local mechanical properties of anatomical subregions within the rat hippocampus, the atomic force microscope (AFM) was adapted for use on living brain tissue. The AFM provided advantages over alternative methods for measuring local mechanical properties of brain because of its high spatial resolution, high sensitivity, and ability to measure live samples under physiologic conditions. From AFM indentations, a mean pointwise or depth-dependent apparent elastic modulus, Ě, was determined for the following hippocampal subregions: CA1 pyramidal cell layer (CA1P) and stratum radiatum (CA1SR), CA3 pyramidal cell layer (CA3P) and stratum radiatum (CA3SR), and the dentate gyrus (DG). For all regions, Ě was indentation-depth-dependent, reflecting the nonlinearity of brain tissue. At an indentation depth of 3 μm, Ě was 234 ± 152 Pa...

Tissue-engineered myocardial patch derived from extracellular matrix provides regional mechanical function.

Abstract: Background— Extracellular matrix (ECM), a tissue-engineered scaffold, recently demonstrated cardiomyocyte population after myocardial implantation. Surgical restoration of myocardium frequently uses Dacron as a myocardial patch. We hypothesized that an ECM-derived myocardial patch would provide a mechanical benefit not seen with Dacron. Methods and Results— Using a canine model, a full thickness defect in the right ventricle was repaired with either Dacron or ECM. A third group had no surgery and determined baseline RV function. Eight weeks later, global systolic function was assessed by the preload recruitable stroke work relationship. Regional systolic function was measured by systolic area contraction (SAC), calculated by high density mechanical mapping. Tau was used to assess global diastolic function. Recoil rate and diastolic shear were used as measures of regional diastolic function. After functional data acquisition, tissue was fixed for histological evaluation. Global systolic and diastolic functions were similar at baseline and after ECM and Dacron implantation. Regional systolic function was greater in the ECM group compared with the Dacron group (SAC: 4.1±0.9% versus −1.8±1.1, P <0.05). Regional diastolic function was also greater in the ECM group (recoil rate (° sec−1): −44±7 versus −17±2, ECM versus Dacron; P <0.05). Immunohistochemical analysis revealed cardiomyocytes in the ECM implant region, a finding not seen with Dacron. Conclusion— At 8 weeks, an ECM-derived tissue-engineered myocardial patch provides regional mechanical function, likely related to cardiomyocyte population. These results are in sharp contrast to Dacron, a commonly used myocardial patch.

Small Molecule-Mediated Directed Differentiation of Human Embryonic Stem Cells Toward Ventricular Cardiomyocytes

Abstract: The generation of human ventricular cardiomyocytes from human embryonic stem cells and/or induced pluripotent stem cells could fulfill the demand for therapeutic applications and in vitro pharmacological research; however, the production of a homogeneous population of ventricular cardiomyocytes remains a major limitation. By combining small molecules and growth factors, we developed a fully chemically defined, directed differentiation system to generate ventricular-like cardiomyocytes (VCMs) from human embryonic stem cells and induced pluripotent stem cells with high efficiency and reproducibility. Molecular characterization revealed that the differentiation recapitulated the developmental steps of cardiovascular fate specification. Electrophysiological analyses further illustrated the generation of a highly enriched population of VCMs. These chemically induced VCMs exhibited the expected cardiac electrophysiological and calcium handling properties as well as the appropriate chronotropic responses to cardioactive compounds. In addition, using an integrated computational and experimental systems biology approach, we demonstrated that the modulation of the canonical Wnt pathway by the small molecule IWR-1 plays a key role in cardiomyocyte subtype specification. In summary, we developed a reproducible and efficient experimental platform that facilitates a chemical genetics-based interrogation of signaling pathways during cardiogenesis that bypasses the limitations of genetic approaches and provides a valuable source of ventricular cardiomyocytes for pharmacological screenings as well as cell replacement therapies.

The Pharmacological Basis of Therapeutics

Abstract: The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

Heat and Mass Transfer

Abstract: Thermophysical Properties Research Literature Retrieval Guide Edited by Y. S. Touloukian, J. K. Gerritsen and N. Y. Moore Second edition, revised and expanded. Book 1: Pp. xxi + 819. Book 2: Pp.621. Book 3: Pp. ix + 1315. (New York: Plenum Press, 1967.) n.p.