Ryan Hoffman | Touro College (original) (raw)

Papers by Ryan Hoffman

Kidney International, 2017

Vascular progenitor cells show promise for the treatment of microvasculature endothelial injury. ... more Vascular progenitor cells show promise for the treatment of microvasculature endothelial injury. We investigated the function of renal artery progenitor cells derived from radical nephrectomy patients, in animal models of acute ischemic and hyperperfusion injuries. Present in human adventitia, CD34positive/CD105negative cells were clonal and expressed transcription factors Sox2/Oct4 as well as surface markers CXCR4 (CD184)/KDR(CD309) consistent with endothelial progenitor cells. Termed renal artery-derived vascular progenitor cells (RAPC), injected cells were associated with decreased serum creatinine after ischemia/reperfusion, reduced albuminuria after hyperperfusion, and improved blood flow in both models. A small population of RAPC integrated with the renal microvasculature following either experimental injury. At a cellular level, RAPC promoted local endothelial migration in co-culture. Profiling of RAPC microRNA identified high levels of miRNA 218; also found at high levels in exosomes isolated from RAPC conditioned media after cell contact for 24 hours. After hydrogen peroxide-induced endothelial injury, RAPC exosomes harbored Robo-1 transcript; a gene known to be regulated by mir218. Such exosomes enhanced endothelial cell migration in culture in the absence of RAPC. Thus, our work shows the

Kidney International, 2014

Vascular inflammation is a major contributor to the severity of acute kidney injury. In the conte... more Vascular inflammation is a major contributor to the severity of acute kidney injury. In the context of vasospasm-independent reperfusion injury we studied the potential anti-inflammatory role of the Gα-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 minute injury, although post-ischemic renal arteriolar diameter was equal to the wild type early after injury. A 10 minute unilateral injury was performed to study reperfusion without vasospasm. Eighteen hours after injury blood flow was decreased in the inner cortex of wild type mice with preservation of tubular architecture. Angiotensin II levels in the kidneys of wild type and transgenic mice were elevated in a sub-vasoconstrictive range 12 and 18 hours after injury. Angiotensin II stimulated pre-glomerular vascular smooth muscle cells (VSMC) to secrete the macrophage chemoattractant, RANTES; a process decreased by angiotensin II R2 (AT2) inhibition. However, RANTES increased when RGS4 expression was suppressed implicating Gα protein activation in an AT2-RGS4-dependent pathway. RGS4 function, specific to VSMC, was tested in a conditional VSMCspecific RGS4 knockout showing high macrophage density by T2 MRI compared to transgenic and non-transgenic mice after the 10 minute injury. Arteriolar diameter of this knockout was unchanged at successive time points after injury. Thus, RGS4 expression, specific to renal VSMC,

Arteriosclerosis Thrombosis and Vascular Biology, May 1, 2014

2016 IEEE-EMBS International Conference on Biomedical and Health Informatics (BHI), 2016

The Big Data era in Biomedical research has resulted in large-cohort data repositories such as Th... more The Big Data era in Biomedical research has resulted in large-cohort data repositories such as The Cancer Genome Atlas (TCGA). These repositories routinely contain hundreds of matched patient samples for genomic, proteomic, imaging, and clinical data modalities, enabling holistic and multi-modal integrative analysis of human disease. Using TCGA renal and ovarian cancer data, we conducted a novel investigation of multi-modal data integration by combining histopathological image and RNA-seq data. We compared the performances of two integrative prediction methods: majority vote and stacked generalization. Results indicate that integration of multiple data modalities improves prediction of cancer grade and outcome. Specifically, stacked generalization, a method that integrates multiple data modalities to produce a single prediction result, outperforms both single-data-modality prediction and majority vote. Moreover, stacked generalization reveals the contribution of each data modality (and specific features within each data modality) to the final prediction result and may provide biological insights to explain prediction performance.

Circulation, Nov 26, 2013

Human fsnI, sssTnI and cTnI were retrieved from GenBank accessions gi1351297, gi437009 and gi3014... more Human fsnI, sssTnI and cTnI were retrieved from GenBank accessions gi1351297, gi437009 and gi30141910. Three human TnT isoforms were also characterized: fsTnT (gi33518637), ssTnT (gi1174800), and cTnT (gi408217). The amino acid sequences were analyzed with the N' Met present. Hydrophobic cluster analysis was performed using a webserver located at http://bioserv-.rpbs.jussieu.fr, authored by C. Gaboriaud, V. Bissery, T. Benchetrit, and J.P. Mornon. FoldIndex was run with a a step size of 1 residue and a window size of 51 residues using the webserver at with default settings (2\% false positive threshold, using PSI-PRED).

The Faseb Journal, Apr 1, 2013

Data Revues 10727515 V199i5 S1072751504009238, Aug 24, 2011

... JR Dennison, Jerilyn Brunson, Ryan Hoffman, Jonathon Abbott, Clint Thomson and Alec Sim, “Mea... more ... JR Dennison, Jerilyn Brunson, Ryan Hoffman, Jonathon Abbott, Clint Thomson and Alec Sim, “Measurements of Electrical and Electron Emission Properties of Highly Insulating Materials,” Air Force Office of Scientific Research Workshop On Multifunctional Materials, Keystone III ...

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2014

Automated processing of digital histopathology slides has the potential to streamline patient car... more Automated processing of digital histopathology slides has the potential to streamline patient care and provide new tools for cancer classification and grading. Before automatic analysis is possible, quality control procedures are applied to ensure that each image can be read consistently. One important quality control step is color normalization of the slide image, which adjusts for color variances (batch-effects) caused by differences in stain preparation and image acquisition equipment. Color batch-effects affect color-based features and reduce the performance of supervised color segmentation algorithms on images acquired separately. To identify an optimal normalization technique for histopathological color segmentation applications, five color normalization algorithms were compared in this study using 204 images from four image batches. Among the normalization methods, two global color normalization methods normalized colors from all stain simultaneously and three stain color nor...

Pain medicine (Malden, Mass.), 2014

This study aims to compare radiofrequency (RF) heat lesion size across electrodes and generator s... more This study aims to compare radiofrequency (RF) heat lesion size across electrodes and generator settings available for interventional pain management. Monopolar lesions are generated ex vivo in animal tissue using sharp cannulae with tip diameters 23, 22, 20, 18, 16 gauge; tip lengths 5, 6, 10, 15 mm; set temperatures 60, 70, 80, 90°C; set times 1, 1.5, 2, 3, 5, 10 minutes. Lesions are generated using the RRE electrode, cooled RF, and parallel-tip bipolar RF for comparison. Lesion sizes are assessed by automated photographic temperature inference from over 400 lesions, using multiple lesions per configuration. Monopolar lesion width and length increase with each factor (P < 0.001). Increasing cannula diameter from 22 to 16 gauge increases average lesion width 58-65% (3-4 mm) at 80°C and 2 minutes. Increasing temperature from 60°C to 90°C increases lesion width 108-152% at 2 minutes. Although dimensions grow most rapidly over the first minute, average lesion width is 11-20% larger...

Advances in Experimental Medicine and Biology, 2007

Page 1. 7 DISPOSITION AND DYNAMICS: INTERDOMAIN ORIENTATIONS IN TROPONIN Ryan MB Hoffman and Bria... more Page 1. 7 DISPOSITION AND DYNAMICS: INTERDOMAIN ORIENTATIONS IN TROPONIN Ryan MB Hoffman and Brian D. Sykes Regulatory Mechanisms of Striated Muscle Contraction Edited by Ebashi and Ohtsuki, Springer, 2007 59 7.1. A PARADIGMATIC PROTEIN ...

Infotech@Aerospace 2012, 2012

Journal of Virology, 2014

216 words 20 Text: 6,492 words 21 22 23 24 25 26 27 28 29 30 2 ABSTRACT 31 32

Journal of Clinical Investigation, 2014

In atherosclerosis, plaques preferentially develop in arterial regions of disturbed blood flow (d... more In atherosclerosis, plaques preferentially develop in arterial regions of disturbed blood flow (d-flow), which alters endothelial gene expression and function. Here, we determined that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase-dependent (DNMT-dependent) manner. Induction of d-flow by partial carotid ligation surgery in a murine model induced DNMT1 in arterial endothelium. In cultured endothelial cells, DNMT1 was enhanced by oscillatory shear stress (OS), and reduction of DNMT with either the inhibitor 5-aza-2′-deoxycytidine (5Aza) or siRNA markedly reduced OS-induced endothelial inflammation. Moreover, administration of 5Aza reduced lesion formation in 2 mouse models of atherosclerosis. Using both reduced representation bisulfite sequencing (RRBS) and microarray, we determined that d-flow in the carotid artery resulted in hypermethylation within the promoters of 11 mechanosensitive genes and that 5Aza treatment restored normal methylation patterns. Of the identified genes, HoxA5 and Klf3 encode transcription factors that contain cAMP response elements, suggesting that the methylation status of these loci could serve as a mechanosensitive master switch in gene expression. Together, our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.

Bulletin of the American …, 2008

We describe the results of a project to design, build, calibrate and test a system to measure the... more We describe the results of a project to design, build, calibrate and test a system to measure the surface charge on an insulator as a function of time and position in situ in a vacuum chamber. In our system, surface charge is created when an insulator is bombarded by fast ...

Proteins: Structure, Function, and Bioinformatics, 2008

Various intrinsic disorder (ID) prediction algorithms were applied to the three tissue isoforms o... more Various intrinsic disorder (ID) prediction algorithms were applied to the three tissue isoforms of troponin I (TnI). The results were interpreted in terms of the known structure and dynamics of troponin. In line with previous results, all isoforms of TnI were predicted to have large stretches of ID. The predictions show that the C-termini of all isoforms are extensively disordered as is the N-terminal extension of the cardiac isoform. Cardiac TnI likely belongs to the group of intrinsically disordered signalling hub proteins. For a given portion of the protein sequence, most ID prediction approaches indicate isoform-dependent variations in the probability of disorder. Comparison of machine learning and physically based approaches suggests the ID variations are only partially attributable to local variations in the ratio of charged to hydrophobic residues. The VSL2B algorithm predicts the largest variations in ID across the isoforms, with the cardiac isoform having the highest probability of structured regions, and the fast-skeletal isoform having no intrinsic structure. The region corresponding to residues 57-95 of the fast-skeletal isoform, known to form a coiled coil substructure with troponin T, was highly variable between isoforms. The isoform-specific ID variations may have mechanistic significance, modulating the extent to which conformational fluctuations in tropomyosin are communicated to the troponin complex. We discuss structural mechanisms for this communication. Overall, the results motivate the development of predictors designed to address relative levels of disorder between highly similar proteins.