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Correction: Magnetized Chitosan Hydrogel And Silk Fibroin, Reinforced With Pva: A Novel Nanobiocomposite For Biomedical And Hyperthermia Applications, Reza Eivazzadeh-Keihan, Zeinab Pajoum, Hooman Aghamirza Moghim Aliabadi, Adibeh Mohammadi, Amir Kashtiaray, Milad Salimi Bani, Banafshe Pishva, Ali Maleki, Majid M. Heravi, Mohammad Mahdavi, Elaheh Ziaei Ziabari Oct 2025

Correction: Magnetized Chitosan Hydrogel And Silk Fibroin, Reinforced With Pva: A Novel Nanobiocomposite For Biomedical And Hyperthermia Applications, Reza Eivazzadeh-Keihan, Zeinab Pajoum, Hooman Aghamirza Moghim Aliabadi, Adibeh Mohammadi, Amir Kashtiaray, Milad Salimi Bani, Banafshe Pishva, Ali Maleki, Majid M. Heravi, Mohammad Mahdavi, Elaheh Ziaei Ziabari

Rothman Institute Papers

The authors regret that they omitted a citation to ref. 1 in their original article. This citation should be included in Section 3 (Result and discussion) before Section 3.1 (FT-IR spectroscopy and XRD analysis). The authors wish to add the following paragraphs to the discussion section of the original article, to be read in Section 3 (Result and discussion) before Section 3.1 (FT-IR spectroscopy and XRD analysis), after the sentence “.Finally, hyperthermia application was appraised and all results were evaluated.” in order to clarify the novelty of this work over ref. 1. In the previous work, we developed a multifunctional …


Tryptophan Kynurenine Pathway-Based Imaging Agents For Brain Disorders And Oncology-From Bench To Bedside, Erik Stauff, Wenqi Xu, Heidi H. Kecskemethy, Sigrid A. Langhans, Vinay V. R. Kandula, Lauren W. Averill, Xuyi Yue Jan 2025

Tryptophan Kynurenine Pathway-Based Imaging Agents For Brain Disorders And Oncology-From Bench To Bedside, Erik Stauff, Wenqi Xu, Heidi H. Kecskemethy, Sigrid A. Langhans, Vinay V. R. Kandula, Lauren W. Averill, Xuyi Yue

Jefferson Hospital Staff Papers and Presentations

Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11. A newer generation of Trp-based imaging agents using the longer half-lived and commercially available isotopes, such as fluorine-18 and iodine-124, are being developed. The newly developed amino acid-based tracers have been demonstrated to have favorable radiochemical and imaging characteristics in pre-clinical studies. However, many barriers still exist in the clinical translation of …


Insulin Resistance In Women Correlates With Chromatin Histone Lysine Acetylation, Inflammatory Signaling, And Accelerated Aging, Christina Vidal, Jackelyn Alva-Ornelas, Nancy Zhuo Chen, Parijat Senapati, Jerneja Tomsic, Vanessa Myriam Robles, Cristal Resto, Nancy Sanchez, Angelica Sanchez, Terry Hyslop, Nour Emwas, Dana Aljaber, Nick Bachelder, Ernest Martinez, David Ann, Veronica Jones, Robert Winn, Lucio Miele, Augusto Ochoa, Eric Dietze, Rama Natarajan, Dustin Schones, Victoria Seewaldt Aug 2024

Insulin Resistance In Women Correlates With Chromatin Histone Lysine Acetylation, Inflammatory Signaling, And Accelerated Aging, Christina Vidal, Jackelyn Alva-Ornelas, Nancy Zhuo Chen, Parijat Senapati, Jerneja Tomsic, Vanessa Myriam Robles, Cristal Resto, Nancy Sanchez, Angelica Sanchez, Terry Hyslop, Nour Emwas, Dana Aljaber, Nick Bachelder, Ernest Martinez, David Ann, Veronica Jones, Robert Winn, Lucio Miele, Augusto Ochoa, Eric Dietze, Rama Natarajan, Dustin Schones, Victoria Seewaldt

Kimmel Cancer Center Faculty Papers

BACKGROUND: Epigenetic changes link medical, social, and environmental factors with cardiovascular and kidney disease and, more recently, with cancer. The mechanistic link between metabolic health and epigenetic changes is only starting to be investigated. In our in vitro and in vivo studies, we performed a broad analysis of the link between hyperinsulinemia and chromatin acetylation; our top "hit" was chromatin opening at H3K9ac.

METHODS: Building on our published preclinical studies, here, we performed a detailed analysis of the link between insulin resistance, chromatin acetylation, and inflammation using an initial test set of 28 women and validation sets of 245, 22, …


Risk Factors Associated With Pyogenic Spinal Infections Among Intravenous Drug Users And Nonusers, Vivek Biololikar, Brendan Gleason, Lee Kripke, Robert Merrill, Colin Whitaker, Jon Handal Jul 2024

Risk Factors Associated With Pyogenic Spinal Infections Among Intravenous Drug Users And Nonusers, Vivek Biololikar, Brendan Gleason, Lee Kripke, Robert Merrill, Colin Whitaker, Jon Handal

Einstein Health Papers

PURPOSE: To identify the differences in patient factors, presentation, treatment course, and outcomes of intravenous drug users (IVDA) vs. nonusers (non-IVDA) presenting with pyogenic spinal infections.

METHODS: We identified all cases involving spinal infections at our institution between May 2017 and January 2023. Postsurgical infections were excluded, and patients were separated into IVDA and non-IVDA groups. The patient charts were reviewed and analyzed for statistical or clinically significant differences using RStudio (2019 version 3.6.2). Our institutional review board approved this study, IRB# 2020-277, iRISID-2023-1384.

RESULTS: Fifty patients (29 males and 21 females) with primary pyogenic spinal infections were included in …


Scar Formation In The Presence Of Mitomycin C And The Anti-Fibrotic Antibody In A Rabbit Model Of Glaucoma Microsurgery: A Pilot Study, Aakriti Garg Shukla, Tatyana Milman, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala Apr 2023

Scar Formation In The Presence Of Mitomycin C And The Anti-Fibrotic Antibody In A Rabbit Model Of Glaucoma Microsurgery: A Pilot Study, Aakriti Garg Shukla, Tatyana Milman, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala

Wills Eye Hospital Papers

Purpose: This study aimed to evaluate the utility of a rationally engineered antibody that directly blocks collagen fibrillogenesis to reduce scar tissue formation associated with subconjunctival glaucoma surgery.

Material and methods: Fourteen eyes of 7 adult rabbits underwent glaucoma filtering surgery using XEN 45 Gel Stent. The rabbits’ eyes were divided randomly into three treatment groups: (i) treated with the antibody, (ii) treated with mitomycin C, and (iii) treated with the antibody and mitomycin C. Following surgeries, the intraocular pressure and bleb appearance were evaluated in vivo. The rabbits were sacrificed 8 weeks after the surgery, and their eyes were …


Magnetized Chitosan Hydrogel And Silk Fibroin, Reinforced With Pva: A Novel Nanobiocomposite For Biomedical And Hyperthermia Applications, Reza Eivazzadeh-Keihan, Zeinab Pajoum, Hooman Aghamirza Moghim Aliabadi, Adibeh Mohammadi, Amir Kashtiaray, Milad Salimi Bani, Banafshe Pishva, Ali Maleki, Majid M Heravi, Mohammad Mahdavi, Elaheh Ziaei Ziabari Mar 2023

Magnetized Chitosan Hydrogel And Silk Fibroin, Reinforced With Pva: A Novel Nanobiocomposite For Biomedical And Hyperthermia Applications, Reza Eivazzadeh-Keihan, Zeinab Pajoum, Hooman Aghamirza Moghim Aliabadi, Adibeh Mohammadi, Amir Kashtiaray, Milad Salimi Bani, Banafshe Pishva, Ali Maleki, Majid M Heravi, Mohammad Mahdavi, Elaheh Ziaei Ziabari

Department of Orthopaedic Surgery Faculty Papers

Herein, a multifunctional nanobiocomposite was designed for biological application, amongst which hyperthermia cancer therapy application was specifically investigated. This nanobiocomposite was fabricated based on chitosan hydrogel (CS), silk fibroin (SF), water-soluble polymer polyvinyl alcohol (PVA) and iron oxide magnetic nanoparticles (Fe3O4 MNPs). CS and SF as natural compounds were used to improve the biocompatibility, biodegradability, adhesion and cell growth properties of the nanobiocomposite that can prepare this nanocomposite for the other biological applications such as wound healing and tissue engineering. Since the mechanical properties are very important in biological applications, PVA polymer was used to increase the …


Approximating Scaffold Printability Utilizing Computational Methods, Ashkan Sedigh, Pejman Ghelich, Jacob Quint, Evelyn C Mollocana-Lara, Mohamadmahdi Samandari, Ali Tamayol, Ryan E. Tomlinson Feb 2023

Approximating Scaffold Printability Utilizing Computational Methods, Ashkan Sedigh, Pejman Ghelich, Jacob Quint, Evelyn C Mollocana-Lara, Mohamadmahdi Samandari, Ali Tamayol, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Bioprinting facilitates the generation of complex, three-dimensional (3D), cell-based constructs for various applications. Although multiple bioprinting technologies have been developed, extrusion-based systems have become the dominant technology due to the diversity of materials (bioinks) that can be utilized, either individually or in combination. However, each bioink has unique material properties and extrusion characteristics that affect bioprinting utility, accuracy, and precision. Here, we have extended our previous work to achieve high precision (i.e. repeatability) and printability across samples by optimizing bioink-specific printing parameters. Specifically, we hypothesized that a fuzzy inference system (FIS) could be used as a computational method to address …


Epigenetic Basis Of Diabetic Vasculopathy, Theja Bhamidipati, Manishekhar Kumar, Sumit S. Verma, Sedat Kacar, Diamond Reese, Michelle M. Martinez, Malgorzata M. Kamocka, Kenneth W. Dunn, Chandan K. Sen, Kanhaiya Singh Dec 2022

Epigenetic Basis Of Diabetic Vasculopathy, Theja Bhamidipati, Manishekhar Kumar, Sumit S. Verma, Sedat Kacar, Diamond Reese, Michelle M. Martinez, Malgorzata M. Kamocka, Kenneth W. Dunn, Chandan K. Sen, Kanhaiya Singh

Einstein Health Papers

Type 2 diabetes mellitus (T2DM) causes peripheral vascular disease because of which several blood-borne factors, including vital nutrients fail to reach the affected tissue. Tissue epigenome is sensitive to chronic hyperglycemia and is known to cause pathogenesis of micro- and macrovascular complications. These vascular complications of T2DM may perpetuate the onset of organ dysfunction. The burden of diabetes is primarily because of a wide range of complications of which nonhealing diabetic ulcers represent a major component. Thus, it is imperative that current research help recognize more effective methods for the diagnosis and management of early vascular injuries. This review addresses …


Recommendations For Daytime, Evening, And Nighttime Indoor Light Exposure To Best Support Physiology, Sleep, And Wakefulness In Healthy Adults, Timothy M Brown, George Brainard, Christian Cajochen, Charles A Czeisler, John P Hanifin, Steven W Lockley, Robert J Lucas, Mirjam Münch, John B O'Hagan, Stuart N Peirson, Luke L A Price, Till Roenneberg, Luc J M Schlangen, Debra J Skene, Manuel Spitschan, Céline Vetter, Phyllis C Zee, Kenneth P Wright Mar 2022

Recommendations For Daytime, Evening, And Nighttime Indoor Light Exposure To Best Support Physiology, Sleep, And Wakefulness In Healthy Adults, Timothy M Brown, George Brainard, Christian Cajochen, Charles A Czeisler, John P Hanifin, Steven W Lockley, Robert J Lucas, Mirjam Münch, John B O'Hagan, Stuart N Peirson, Luke L A Price, Till Roenneberg, Luc J M Schlangen, Debra J Skene, Manuel Spitschan, Céline Vetter, Phyllis C Zee, Kenneth P Wright

Department of Neurology Faculty Papers

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Prevailing patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, international standard provides a SI-compliant way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, …


Astrocyte-Secreted Chordin-Like 1 Regulates Spine Density After Ischemic Injury, Elena Blanco-Suarez, Nicola J Allen Mar 2022

Astrocyte-Secreted Chordin-Like 1 Regulates Spine Density After Ischemic Injury, Elena Blanco-Suarez, Nicola J Allen

Department of Neuroscience Faculty Papers

Ischemic injury occurs when the brain is deprived of blood flow, preventing cells from receiving essential nutrients. The injury core is the brain region directly deprived and is surrounded by the peri-infarct area, the region with recovery potential. In the peri-infarct area neurons undergo acute loss of dendritic spines, which modifies synaptic plasticity and determines neuronal survival. Astrocytes can be protective or detrimental to the ischemic injury response depending on the specific stage, yet we lack clear understanding of the underlying mechanisms. Chordin-like 1 (Chrdl1) is an astrocyte-secreted protein that promotes synaptic maturation and limits experience-dependent plasticity in the mouse …


Ghost Mitochondria Drive Metastasis Through Adaptive Gcn2/Akt Therapeutic Vulnerability, Jagadish C Ghosh, Michela Perego, Ekta Agarwal, Irene Bertolini, Yuan Wang, Aaron R Goldman, Hsin-Yao Tang, Andrew V Kossenkov, Catherine J Libby, Lucia R Languino, Edward F Plow, Annamaria Morotti, Luisa Ottobrini, Marco Locatelli, David W Speicher, M Cecilia Caino, Joel Cassel, Joseph M Salvino, Marie E Robert, Valentina Vaira, Dario C Altieri Feb 2022

Ghost Mitochondria Drive Metastasis Through Adaptive Gcn2/Akt Therapeutic Vulnerability, Jagadish C Ghosh, Michela Perego, Ekta Agarwal, Irene Bertolini, Yuan Wang, Aaron R Goldman, Hsin-Yao Tang, Andrew V Kossenkov, Catherine J Libby, Lucia R Languino, Edward F Plow, Annamaria Morotti, Luisa Ottobrini, Marco Locatelli, David W Speicher, M Cecilia Caino, Joel Cassel, Joseph M Salvino, Marie E Robert, Valentina Vaira, Dario C Altieri

Department of Cancer Biology Faculty Papers

Cancer metabolism, including in mitochondria, is a disease hallmark and therapeutic target, but its regulation is poorly understood. Here, we show that many human tumors have heterogeneous and often reduced levels of Mic60, or Mitofilin, an essential scaffold of mitochondrial structure. Despite a catastrophic collapse of mitochondrial integrity, loss of bioenergetics, and oxidative damage, tumors with Mic60 depletion slow down cell proliferation, evade cell death, and activate a nuclear gene expression program of innate immunity and cytokine/chemokine signaling. In turn, this induces epithelial-mesenchymal transition (EMT), activates tumor cell movements through exaggerated mitochondrial dynamics, and promotes metastatic dissemination in vivo. In …


Activity-Dependent Modulation Of Synapse-Regulating Genes In Astrocytes, Isabella Farhy-Tselnicker, Matthew M Boisvert, Hanqing Liu, Cari Dowling, Galina A Erikson, Elena Blanco-Suarez, Chen Farhy, Maxim N Shokhirev, Joseph R Ecker, Nicola J Allen Sep 2021

Activity-Dependent Modulation Of Synapse-Regulating Genes In Astrocytes, Isabella Farhy-Tselnicker, Matthew M Boisvert, Hanqing Liu, Cari Dowling, Galina A Erikson, Elena Blanco-Suarez, Chen Farhy, Maxim N Shokhirev, Joseph R Ecker, Nicola J Allen

Department of Neurosurgery Faculty Papers

Astrocytes regulate the formation and function of neuronal synapses via multiple signals, however, what controls regional and temporal expression of these signals during development is unknown. We determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually-evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expression of synapse-regulating genes and synaptic development are also altered when astrocyte signaling is blunted by diminishing calcium release from …


Simultaneous Ck2/Tnik/Dyrk1 Inhibition By 108600 Suppresses Triple Negative Breast Cancer Stem Cells And Chemotherapy-Resistant Disease., Katsutoshi Sato, Amol A. Padgaonkar, Stacey J. Baker, Stephen C. Cosenza, Olga Rechkoblit, D.R.C. Venkata Subbaiah, Josep Domingo-Domenech, Alison Bartkowski, Elisa R. Port, Aneel K. Aggarwal, M. V. Ramana Reddy, Hanna Y. Irie, E. Premkumar Reddy Aug 2021

Simultaneous Ck2/Tnik/Dyrk1 Inhibition By 108600 Suppresses Triple Negative Breast Cancer Stem Cells And Chemotherapy-Resistant Disease., Katsutoshi Sato, Amol A. Padgaonkar, Stacey J. Baker, Stephen C. Cosenza, Olga Rechkoblit, D.R.C. Venkata Subbaiah, Josep Domingo-Domenech, Alison Bartkowski, Elisa R. Port, Aneel K. Aggarwal, M. V. Ramana Reddy, Hanna Y. Irie, E. Premkumar Reddy

Department of Medical Oncology Faculty Papers

Triple negative breast cancer (TNBC) remains challenging because of heterogeneous responses to chemotherapy. Incomplete response is associated with a greater risk of metastatic progression. Therefore, treatments that target chemotherapy-resistant TNBC and enhance chemosensitivity would improve outcomes for these high-risk patients. Breast cancer stem cell-like cells (BCSCs) have been proposed to represent a chemotherapy-resistant subpopulation responsible for tumor initiation, progression and metastases. Targeting this population could lead to improved TNBC disease control. Here, we describe a novel multi-kinase inhibitor, 108600, that targets the TNBC BCSC population. 108600 treatment suppresses growth, colony and mammosphere forming capacity of BCSCs and induces G2M arrest …


Spatially Fractionated Radiation Therapy: History, Present And The Future, Weisi Yan, Mohammad K. Khan, Xiaodong Wu, Charles B. Simone Ii, Jiajin Fan, Eric Gressen, Xin Zhang, Charles L. Limoli, Houda Bahig, Slavisa Tubin, Waleed F. Mourad Jan 2020

Spatially Fractionated Radiation Therapy: History, Present And The Future, Weisi Yan, Mohammad K. Khan, Xiaodong Wu, Charles B. Simone Ii, Jiajin Fan, Eric Gressen, Xin Zhang, Charles L. Limoli, Houda Bahig, Slavisa Tubin, Waleed F. Mourad

Department of Radiation Oncology Faculty Papers

No abstract provided.


Efficient And Robust Nk-Cell Transduction With Baboon Envelope Pseudotyped Lentivector., Aurelien B L Colamartino, William Lemieux, Panojot Bifsha, Simon Nicoletti, Nitin Chakravarti, Joaquín Sanz, Hugo Roméro, Silvia Selleri, Kathie Béland, Mélanie Guiot, Camille Tremblay-Laganière, Renée Dicaire, Luis Barreiro, Dean A Lee, Els Verhoeyen, Elie Haddad Dec 2019

Efficient And Robust Nk-Cell Transduction With Baboon Envelope Pseudotyped Lentivector., Aurelien B L Colamartino, William Lemieux, Panojot Bifsha, Simon Nicoletti, Nitin Chakravarti, Joaquín Sanz, Hugo Roméro, Silvia Selleri, Kathie Béland, Mélanie Guiot, Camille Tremblay-Laganière, Renée Dicaire, Luis Barreiro, Dean A Lee, Els Verhoeyen, Elie Haddad

Department of Medical Oncology Faculty Papers

NK-cell resistance to transduction is a major technical hurdle for developing NK-cell immunotherapy. By using Baboon envelope pseudotyped lentiviral vectors (BaEV-LVs) encoding eGFP, we obtained a transduction rate of 23.0 ± 6.6% (mean ± SD) in freshly-isolated human NK-cells (FI-NK) and 83.4 ± 10.1% (mean ± SD) in NK-cells obtained from the NK-cell Activation and Expansion System (NKAES), with a sustained transgene expression for at least 21 days. BaEV-LVs outperformed Vesicular Stomatitis Virus type-G (VSV-G)-, RD114- and Measles Virus (MV)- pseudotyped LVs (p < 0.0001). mRNA expression of both BaEV receptors, ASCT1 and ASCT2, was detected in FI-NK and NKAES, with higher expression in NKAES. Transduction with BaEV-LVs encoding for CAR-CD22 resulted in robust CAR-expression on 38.3 ± 23.8% (mean ± SD) of NKAES cells, leading to specific killing of NK-resistant pre-B-ALL-RS4;11 cell line. Using a larger vector encoding a dual CD19/CD22-CAR, we were able to transduce and re-expand dual-CAR-expressing NKAES, even with lower viral titer. These dual-CAR-NK efficiently killed both CD19KO- and CD22KO-RS4;11 cells. Our results suggest that BaEV-LVs may efficiently enable NK-cell biological studies and translation of NK-cell-based immunotherapy to the clinic.


A Proline Insertion-Deletion In The Spike Glycoprotein Fusion Peptide Of Mouse Hepatitis Virus Strongly Alters Neuropathology., Manmeet Singh, Abhinoy Kishore, Dibyajyoti Maity, Punnepalli Sunanda, Bankala Krishnarjuna, Sreeparna Vappala, Srinivasarao Raghothama, Lawrence C. Kenyon, Debnath Pal, Jayasri Das Sarma May 2019

A Proline Insertion-Deletion In The Spike Glycoprotein Fusion Peptide Of Mouse Hepatitis Virus Strongly Alters Neuropathology., Manmeet Singh, Abhinoy Kishore, Dibyajyoti Maity, Punnepalli Sunanda, Bankala Krishnarjuna, Sreeparna Vappala, Srinivasarao Raghothama, Lawrence C. Kenyon, Debnath Pal, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Fusion peptides (FPs) in spike proteins are key players mediating early events in cell-to-cell fusion, vital for intercellular viral spread. A proline residue located at the central FP region has often been suggested to have a distinctive role in this fusion event. The spike glycoprotein from strain RSA59 (PP) of mouse hepatitis virus (MHV) contains two central, consecutive prolines in the FP. Here, we report that deletion of one of these proline residues, resulting in RSA59 (P), significantly affected neural cell syncytia formation and viral titers postinfection in vitro. Transcranial inoculation of C57Bl/6 mice with RSA59 (PP) or RSA59 (P) …


Dynamic Molecular Changes During The First Week Of Human Life Follow A Robust Developmental Trajectory., Amy H. Lee, Casey P. Shannon, Nelly Amenyogbe, Tue B. Bennike, Joann Diray-Arce, Olubukola T. Idoko, Erin E. Gill, Rym Ben-Othman, William S. Pomat, Simon D. Van Haren, Kim-Anh Lê Cao, Momoudou Cox, Alansana Darboe, Reza Falsafi, Davide Ferrari, Daniel J. Harbeson, Daniel He, Cai Bing, Samuel J. Hinshaw, Jorjoh Ndure, Jainaba Njie-Jobe, Matthew A. Pettengill, Peter C. Richmond, Rebecca Ford, Gerard Saleu, Geraldine Masiria, John Paul Matlam, Wendy Kirarock, Elishia Roberts, Mehrnoush Malek, Guzmán Sanchez-Schmitz, Amrit Singh, Asimenia Angelidou, Kinga K. Smolen, Diana Vo, Ken Kraft, Kerry Mcenaney, Sofia Vignolo, Arnaud Marchant, Ryan R. Brinkman, Al Ozonoff, Robert E.W. Hancock, Anita H.J. Van Den Biggelaar, Hanno Steen, Scott J. Tebbutt, Beate Kampmann, Ofer Levy, Tobias R. Kollmann Mar 2019

Dynamic Molecular Changes During The First Week Of Human Life Follow A Robust Developmental Trajectory., Amy H. Lee, Casey P. Shannon, Nelly Amenyogbe, Tue B. Bennike, Joann Diray-Arce, Olubukola T. Idoko, Erin E. Gill, Rym Ben-Othman, William S. Pomat, Simon D. Van Haren, Kim-Anh Lê Cao, Momoudou Cox, Alansana Darboe, Reza Falsafi, Davide Ferrari, Daniel J. Harbeson, Daniel He, Cai Bing, Samuel J. Hinshaw, Jorjoh Ndure, Jainaba Njie-Jobe, Matthew A. Pettengill, Peter C. Richmond, Rebecca Ford, Gerard Saleu, Geraldine Masiria, John Paul Matlam, Wendy Kirarock, Elishia Roberts, Mehrnoush Malek, Guzmán Sanchez-Schmitz, Amrit Singh, Asimenia Angelidou, Kinga K. Smolen, Diana Vo, Ken Kraft, Kerry Mcenaney, Sofia Vignolo, Arnaud Marchant, Ryan R. Brinkman, Al Ozonoff, Robert E.W. Hancock, Anita H.J. Van Den Biggelaar, Hanno Steen, Scott J. Tebbutt, Beate Kampmann, Ofer Levy, Tobias R. Kollmann

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Systems biology can unravel complex biology but has not been extensively applied to human newborns, a group highly vulnerable to a wide range of diseases. We optimized methods to extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data fromblood, a volume readily obtained from newborns. Indexing to baseline and applying innovative integrative computational methods reveals dramatic changes along a remarkably stable developmental trajectory over the first week of life. This is most evident in changes of interferon and complement pathways, as well as neutrophil-associated signaling. Validated across two independent cohorts of newborns from West Africa and Australasia, a …


Jefferson Digital Commons Quarterly Report: April-June 2018, Kelsey Duinkerken, Msi, James Copeland, Libt Jul 2018

Jefferson Digital Commons Quarterly Report: April-June 2018, Kelsey Duinkerken, Msi, James Copeland, Libt

Jefferson Digital Commons Reports

This quarterly report includes:

  • New Feature: PlumX Metrics
  • New Feature: CrossRef DOIs
  • College Restructuring
  • Articles
  • CREATE Day Presentations
  • Department of Surgery Resident Research Day
  • Dissertations
  • From the Archives
  • Grand Rounds and Lectures
  • Master of Public Health Capstones
  • Newsletters
  • Pathology Honors Program Student Research Symposium
  • Posters
  • What People are Saying About the JDC


Ependymomas Overexpress Chemoresistance And Dna Repairrelated Proteins, Sherise D. Ferguson, Shouhao Zhou, Joanne Xiu, Yuuri Hashimoto, Nader Sanai, Lyndon Kim, Santosh Kesari, John De Groot, David Spetzler, Amy B. Heimberger Dec 2017

Ependymomas Overexpress Chemoresistance And Dna Repairrelated Proteins, Sherise D. Ferguson, Shouhao Zhou, Joanne Xiu, Yuuri Hashimoto, Nader Sanai, Lyndon Kim, Santosh Kesari, John De Groot, David Spetzler, Amy B. Heimberger

Department of Neurosurgery Faculty Papers

Background: After surgery and radiation, treatment options for ependymoma are few making recurrence a challenging issue. Specifically, the efficacy of chemotherapy at recurrence is limited. We performed molecular profiling on a cohort of ependymoma cases in order to uncover therapeutic targets and to elucidate the molecular mechanisms contributing to treatment resistance. Results: This ependymoma cohort showed minimal alterations in gene amplifications and mutations but had high expression rates of DNA synthesis and repair enzymes such as RRM1 (47%), ERCC1 (48%), TOPO1 (62%) and class III β-tublin (TUBB3) (57%), which are also all associated with chemoresistance. This cohort also had high …


Genetic And Genomic Characterization Of 462 Melanoma Patient-Derived Xenografts, Tumor Biopsies, And Cell Lines., Bradley Garman, Ioannis N. Anastopoulos, Clemens Krepler, Patricia Brafford, Katrin Sproesser, Yuchao Jiang, Bradley Wubbenhorst, Ravi Amaravadi, Joseph Bennett, Marilda Beqiri, David Elder, Keith T. Flaherty, Dennie T. Frederick, Tara C. Gangadhar, Michael Guarino, David Hoon, Giorgos Karakousis, Qin Liu, Nandita Mitra, Nicholas J. Petrelli, Lynn Schuchter, Batool Shannan, Carol L. Shields, Jennifer Wargo, Brandon Wenz, Melissa A. Wilson, Min Xiao, Wei Xu, Xaiowei Xu, Xiangfan Yin, Nancy R. Zhang, Michael A. Davies, Meenhard Herlyn, Katherine L. Nathanson Nov 2017

Genetic And Genomic Characterization Of 462 Melanoma Patient-Derived Xenografts, Tumor Biopsies, And Cell Lines., Bradley Garman, Ioannis N. Anastopoulos, Clemens Krepler, Patricia Brafford, Katrin Sproesser, Yuchao Jiang, Bradley Wubbenhorst, Ravi Amaravadi, Joseph Bennett, Marilda Beqiri, David Elder, Keith T. Flaherty, Dennie T. Frederick, Tara C. Gangadhar, Michael Guarino, David Hoon, Giorgos Karakousis, Qin Liu, Nandita Mitra, Nicholas J. Petrelli, Lynn Schuchter, Batool Shannan, Carol L. Shields, Jennifer Wargo, Brandon Wenz, Melissa A. Wilson, Min Xiao, Wei Xu, Xaiowei Xu, Xiangfan Yin, Nancy R. Zhang, Michael A. Davies, Meenhard Herlyn, Katherine L. Nathanson

Wills Eye Hospital Papers

Tumor-sequencing studies have revealed the widespread genetic diversity of melanoma. Sequencing of 108 genes previously implicated in melanomagenesis was performed on 462 patient-derived xenografts (PDXs), cell lines, and tumors to identify mutational and copy number aberrations. Samples came from 371 unique individuals: 263 were naive to treatment, and 108 were previously treated with targeted therapy (34), immunotherapy (54), or both (20). Models of all previously reported major melanoma subtypes (BRAF, NRAS, NF1, KIT, and WT/WT/WT) were identified. Multiple minor melanoma subtypes were also recapitulated, including melanomas with multiple activating mutations in the MAPK-signaling pathway and chromatin-remodeling gene mutations. These well-characterized …


Nuclear And Mitochondrial Trna-Lookalikes In The Human Genome., Aristeidis G Telonis, Phillipe Loher, Yohei Kirino, Isidore Rigoutsos Sep 2014

Nuclear And Mitochondrial Trna-Lookalikes In The Human Genome., Aristeidis G Telonis, Phillipe Loher, Yohei Kirino, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

We are interested in identifying and characterizing loci of the human genome that harbor sequences resembling known mitochondrial and nuclear tRNAs. To this end, we used the known nuclear and mitochondrial tRNA genes (the "tRNA-Reference" set) to search for "tRNA-lookalikes" and found many such loci at different levels of sequence conservation. We find that the large majority of these tRNA-lookalikes resemble mitochondrial tRNAs and exhibit a skewed over-representation in favor of some mitochondrial anticodons. Our analysis shows that the tRNA-lookalikes have infiltrated specific chromosomes and are preferentially located in close proximity to known nuclear tRNAs (z-score ≤ -2.54, P-value ≤ …


Molecular And Functional Identification Of A Mitochondrial Ryanodine Receptor In Neurons., Regina Jakob, Gisela Beutner, Virendra K Sharma, Yuntao Duan, Robert A Gross, Stephen Hurst, Bong Sook Jhun, Jin O-Uchi, Shey-Shing Sheu Jul 2014

Molecular And Functional Identification Of A Mitochondrial Ryanodine Receptor In Neurons., Regina Jakob, Gisela Beutner, Virendra K Sharma, Yuntao Duan, Robert A Gross, Stephen Hurst, Bong Sook Jhun, Jin O-Uchi, Shey-Shing Sheu

Department of Medicine Faculty Papers

Mitochondrial Ca(2+) controls numerous cell functions, such as energy metabolism, reactive oxygen species generation, spatiotemporal dynamics of Ca(2+) signaling, cell growth and death in various cell types including neurons. Mitochondrial Ca(2+) accumulation is mainly mediated by the mitochondrial Ca(2+) uniporter (MCU), but recent reports also indicate that mitochondrial Ca(2+)-influx mechanisms are regulated not only by MCU, but also by multiple channels/transporters. We previously reported that ryanodine receptor (RyR), which is a one of the main Ca(2+)-release channels at endoplasmic/sarcoplasmic reticulum (SR/ER) in excitable cells, is expressed at the mitochondrial inner membrane (IMM) and serves as a part of the Ca(2+) …


Current Pathophysiological Concepts In Cerebral Small Vessel Disease., Fred Rincon, Clinton B Wright Mar 2014

Current Pathophysiological Concepts In Cerebral Small Vessel Disease., Fred Rincon, Clinton B Wright

Department of Neurology Faculty Papers

The association between cerebral small vessel disease (SVD) - in the form of white matter lesions, infarctions, and hemorrhages - with vascular cognitive impairment (VCI), has mostly been deduced from observational studies. Pathological conditions affecting the small vessels of the brain and leading to SVD have suggested plausible molecular mechanisms involved in vascular damage and their impact on brain function. However, much still needs to be clarified in understanding the pathophysiology of VCI, the role of neurodegenerative processes such as Alzheimer's disease, and the impact of aging itself. In addition, both genetic predispositions and environmental exposures may potentiate the development …


Disruption Of Drosophila Melanogaster Lipid Metabolism Genes Causes Tissue Overgrowth Associated With Altered Developmental Signaling., Takeshi Sasamura, Kenji Matsuno, Mark E Fortini Nov 2013

Disruption Of Drosophila Melanogaster Lipid Metabolism Genes Causes Tissue Overgrowth Associated With Altered Developmental Signaling., Takeshi Sasamura, Kenji Matsuno, Mark E Fortini

Department of Biochemistry and Molecular Biology Faculty Papers

Developmental patterning requires the precise interplay of numerous intercellular signaling pathways to ensure that cells are properly specified during tissue formation and organogenesis. The spatiotemporal function of many developmental pathways is strongly influenced by the biosynthesis and intracellular trafficking of signaling components. Receptors and ligands must be trafficked to the cell surface where they interact, and their subsequent endocytic internalization and endosomal trafficking is critical for both signal propagation and its down-modulation. In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase. …


Adoptive T Cell Therapy For Metastatic Colorectal Cancer, Shauna Ebanks Aug 2013

Adoptive T Cell Therapy For Metastatic Colorectal Cancer, Shauna Ebanks

Summer Training Program in Cancer Immunotherapy

Colorectal cancer is the second leading cause of cancer-related death in US (1). Most of the mortality reflects local, regional and distant metastatic tumors. Cancers that are confined within the wall of the colon are often curable with surgery while tumor cells that have spread into other organs like liver and lung has low curable possibility, even though the chemotherapies and monoclonal antibodies can extend the person's life and improve quality of life(2, 3). Surgery is the main treatment for primary colorectal tumors but recurrence can happen and develop into metastasis. In addition, colorectal cancer …


Scitech Book News Reviews, Susan Fingerman Aug 2013

Scitech Book News Reviews, Susan Fingerman

Sci-Tech News

No abstract provided.


The Complex Transcriptional Landscape Of The Anucleate Human Platelet., Paul F. Bray, Steven E. Mckenzie, Leonard Edelstein, Srikanth Nagalla, Kathleen Delgrosso, Adam Ertel, Joan Kupper, Yi Jing, Eric R. Londin, Phillipe Loher, Huang-Wen Chen, Paolo Fortina, Isidore Rigoutsos Jan 2013

The Complex Transcriptional Landscape Of The Anucleate Human Platelet., Paul F. Bray, Steven E. Mckenzie, Leonard Edelstein, Srikanth Nagalla, Kathleen Delgrosso, Adam Ertel, Joan Kupper, Yi Jing, Eric R. Londin, Phillipe Loher, Huang-Wen Chen, Paolo Fortina, Isidore Rigoutsos

Cardeza Foundation for Hematologic Research

BACKGROUND: Human blood platelets are essential to maintaining normal hemostasis, and platelet dysfunction often causes bleeding or thrombosis. Estimates of genome-wide platelet RNA expression using microarrays have provided insights to the platelet transcriptome but were limited by the number of known transcripts. The goal of this effort was to deep-sequence RNA from leukocyte-depleted platelets to capture the complex profile of all expressed transcripts.

RESULTS: From each of four healthy individuals we generated long RNA (≥40 nucleotides) profiles from total and ribosomal-RNA depleted RNA preparations, as well as short RNA (<40 >nucleotides) profiles. Analysis of ~1 billion reads revealed that coding …


Spinal Tuberculosis: Diagnosis And Management., Mohammad R Rasouli, Maryam Mirkoohi, Alexander R Vaccaro, Kourosh Karimi Yarandi, Vafa Rahimi-Movaghar Dec 2012

Spinal Tuberculosis: Diagnosis And Management., Mohammad R Rasouli, Maryam Mirkoohi, Alexander R Vaccaro, Kourosh Karimi Yarandi, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

The spinal column is involved in less than 1% of all cases of tuberculosis (TB). Spinal TB is a very dangerous type of skeletal TB as it can be associated with neurologic deficit due to compression of adjacent neural structures and significant spinal deformity. Therefore, early diagnosis and management of spinal TB has special importance in preventing these serious complications. In order to extract current trends in diagnosis and medical or surgical treatment of spinal TB we performed a narrative review with analysis of all the articles available for us which were published between 1990 and 2011. Althoug h the …


2012 Commencement For Jefferson Medical College, Jefferson College Of Graduate Studies, And Jefferson School Of Population Health May 2012

2012 Commencement For Jefferson Medical College, Jefferson College Of Graduate Studies, And Jefferson School Of Population Health

Sidney Kimmel Medical College Commencements

No abstract provided.


2012 Commencement For Jefferson Medical College, Jefferson College Of Graduate Studies, And Jefferson School Of Population Health May 2012

2012 Commencement For Jefferson Medical College, Jefferson College Of Graduate Studies, And Jefferson School Of Population Health

Jefferson College of Biomedical Sciences Commencement

No abstract provided.