AbdelAziz Jalil

AbdelAziz Jalil

University of Pennsylvania

H-index: 6

North America-United States

Professor Information

University

University of Pennsylvania

Position

___

Citations(all)

193

Citations(since 2020)

175

Cited By

56

hIndex(all)

6

hIndex(since 2020)

6

i10Index(all)

4

i10Index(since 2020)

4

Email

University Profile Page

University of Pennsylvania

Research & Interests List

Immunology

cancer

antibodies

peptides

Top articles of AbdelAziz Jalil

Tension-suppressed degradation of collagen controls tissue stiffness scaling with fibrillar collagen

Extremely soft tissues such as developing hearts or adult brain contain far less collagen than highly stiff adult tissues such as tendons, but cell and molecular mechanisms for such homeostatic differences remain unclear. We hypothesized that cell-generated or exogenous forces combine with tension-suppressed collagen degradation in order to sculpt extracellular matrix (ECM) collagen levels in tissues. For various mature mice tissues and beating embryonic chick hearts, we find collagen-sensitive second harmonic generation (SHG) image intensity scales non-linearly versus tissue stiffness, aligning well with the results from cellularized gels of collagen. Chick hearts beating at∼ 5% strain maintain collagen levels until their contractile strain is suppressed by myosin-II inhibition and endogenous matrix metalloproteinases (MMPs) then degrade collagens within∼ 30-60 minutes-based on SHG and mass spectrometry …

Authors

Karanvir Saini,Sangkyun Cho,Manu Tewari,Abdelaziz Jalil,Mai Wang,Manasvita Vashisth,Alex Kasznel,Kazuhiro Yamamoto,David M Chenoweth,Dennis E Discher

Journal

Biophysical Journal

Published Date

2023/2/10

Differential roles of extracellular matrix proteins on primary and metastatic pancreatic cancer cells

Pancreatic cancer adenocarcinoma (PDAC) has been reported to be the third highest cause of cancer-related deaths in the United States. PDAC is known for its high proportion of stroma which accounts for 90% of the tumor mass. The stroma is made up of extracellular matrix (ECM) and non-malignant cells such as inflammatory cells, cancer-associated fibroblasts (CAF), and lymphatic and blood vessels. Here, we decoupled the roles of the ECM on PDAC cell lines by culturing the cells on surfaces coated with different ECM proteins. Our data showed that the primary tumor-derived cell lines have different morphology that depends on the ECM proteins on which they are cultured, while metastatic lesion-derived PDAC lines' morphology does not change with respect to the different ECM proteins. Similarly, ECM proteins also modulate the proliferation rate and the gemcitabine sensitivity of the primary tumor PDAC cell lines, but not for the metastatic PDAC lines. Lastly, transcriptomics analysis of the primary tumor PDAC cells cultured on different ECM proteins reveals the regulation of various pathways, such as cell cycle, cell adhesion molecules, and focal adhesion, including the regulation of several integrin genes that are essential for ECM recognition.(which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint this version posted February 23, 2023.; https://doi. org/10.1101/2022.11. 11.516201 doi: bioRxiv preprint

Authors

Olalekan H Usman,Sampath Kumar,Reddick R Walker III,Gengqiang Xie,AbdelAziz R Jalil,Subramanian Ramakrishnan,Lawrence J Dooling,Yue Julia Wang,Jerome Irianto

Journal

bioRxiv

Published Date

2022

Suppressing or enhancing macrophage engulfment through the use of CD47 and related peptides

Foreign particles and microbes are rapidly cleared by macrophages in vivo, although many key aspects of uptake mechanisms remain unclear. “Self” cells express CD47 which functions as an anti-phagocytic ligand for SIRPα on macrophages, particularly when pro-phagocytic ligands such as antibodies are displayed in parallel. Here, we review CD47 and related “Self” peptides as modulators of macrophage uptake. Nanoparticles conjugated with either CD47 or peptides derived from its SIRPα binding site can suppress phagocytic uptake by macrophages in vitro and in vivo, with similar findings for CD47-displaying viruses. Drugs, dyes, and genes as payloads thus show increased delivery to targeted cells. On the other hand, CD47 expression by cancer cells enables such cells to evade macrophages and immune surveillance. This has motivated development of soluble antagonists to CD47-SIRPα, ranging from …

Authors

AbdelAziz R Jalil,Michael P Tobin,Dennis E Discher

Published Date

2022/3/22

Human CD47-Derived Cyclic Peptides Enhance Engulfment of mAb-Targeted Melanoma by Primary Macrophages

CD47 on healthy cells, cancer cells, and even engineered particles can inhibit phagocytic clearance by binding SIRPα on macrophages. To mimic and modulate this interaction with peptides that could be used as soluble antagonists or potentially as bioconjugates to surfaces, we made cyclic “nano-Self” peptides based on the key interaction loop of human CD47. Melanoma cells were studied as a standard preclinical cancer model and were antibody-opsonized to adhere to and activate engulfment by primary mouse macrophages. Phagocytosis in the presence of soluble peptides showed cyclic > wildtype > scrambled activity, with the same trend observed with human cells. Opsonized cells that were not engulfed adhered tightly to macrophages, with opposite trends to phagocytosis. Peptide activity is nonetheless higher in human versus mouse assays, consistent with species differences in CD47–SIRPα. Small …

Authors

AbdelAziz R Jalil,Jason C Andrechak,Brandon H Hayes,David M Chenoweth,Dennis E Discher

Journal

Bioconjugate chemistry

Published Date

2022/3/14

Heterogeneous strains in tissue suppress collagen degradation by collagenases

Tissue homeostasis reflects a balance of synthesis and degradation of collagen, and past studies of homogeneously stressed tissues and collagenous materials indicate that collagen degradation is suppressed by strain. We investigated isolated adult mice tendons and beating embryonic chick hearts to study strain dependent of collagen degradation using label-free second harmonic generation (SHG). Tendon fascicles, natively formed by collagen fibrils primarily orient along the tension-axis, were subjected to heterogeneous strains when deformed by either three-point bending plus adhesion and uniaxial tension using novel mechano-bioreactor. Patterned photo-bleaching of a fluorescent dye and collagen-binding novel Aza-peptide on the fascicles was used to quantify strain. Collagen degradation of the deformed fascicles exposed to exogenous collagenases ie, purified matrix-metalloproteinase-1 (MMP-1) or …

Authors

Karanvir Saini,Manu Tewari,Sangkyun Cho,Manasvita Vashisth,Abdelaziz Jalil,Jason C Andrechak,Alex Kasznel,David Chenoweth,Kazuhiro Yamamoto,Dennis E Discher

Journal

Biophysical Journal

Published Date

2022/2/11

Heterogeneously Strained Tissue Collagen Resists Collagenase Degradation where Strains are High

Tissue homeostasis reflects a balance of synthesis and degradation, and past studies of homogeneously stressed tissues and collagen materials indicate collagen degradation is suppressed by strain. Such processes are studied here in isolated tendons and in beating embryonic hearts. In tendon fascicles, collagen fibrils primarily orient along the tension axis but heterogeneous strains and gradients were induced using two different deformation modes ie heterogeneous (using three-point bending plus adhesion) and uniaxial, with patterned photo-bleaching of a fluorescent dye and collagen-binding peptide on fascicles used to measure strain. Microstructure of" cell-free" fascicles was simultaneously imaged using Second Harmonic Generation (SHG) signal where deformed fascicles were exposed to collagenases ie purified MMP-1 or Bacterial collagenase. Within physiological strain limits (ie∼ 5-8%), the …

Authors

Karanvir Saini,Manu Tewari,Sangkyun Cho,Abdelaziz Jalil,Jerome Irianto,Manasvita Vashisth,Charlotte R Pfeifer,Jason C Andrechak,Lawrence J Dooling,Cory Alvey,Alex Kasznel,David Chenoweth,Kazuhiro Yamamoto,Dennis E Discher

Journal

Biophysical Journal

Published Date

2021/2/12

Heterogeneous strains in tissue collagen show that high strains locally suppress degradation by collagenase

Collagen, the most abundant protein in mammals, contributes to the physical properties of different tissues during development, homeostasis, and disease. The adaptation of physical properties of tissues to mechanical stimuli is thus dependent on the control of tissue collagen levels by well-regulated synthesis and degradation of collagen. Importantly, how various molecular-level events within a tissue sustaining a range of mechanical strains contribute towards maintaining its collagen levels, remains unclear to date. Such molecular level processes in tissues are studied here in the case of isolated tendons consisting of collagen fibrils oriented along tissue loading-axis and beating embryonic hearts to gain understanding of mechanical load dependent tissue sculpting. Using a novel bioreactor design, starved mice tail tendon fascicles were used as a “cell-free” model and were subjected to heterogeneous and uniaxial deformation modes. Patterned photobleaching of fluorescent probes, a novel Aza-peptide or dye, on fascicles used to quantify tissue strains. Tissue microstructure was simultaneously imaged using second harmonic generation (SHG) signal to assess tissue collagen content while deformed fascicle samples were exposed to purified matrix metalloproteinase-1 (MMP-1) or bacterial collagenase (BC). A decrease in the degradation rate (relative to strain-free) was observed for physiological strain limits of tendon tissue (i.e. ∼5-8%) while at higher strains (i.e. pathological) the degradation rate was independent of strain magnitude changes. Interestingly, the strain dependence of degradation rate was independent of cleavage-site …

Authors

K Saini,M Tiwari,S Cho,A Jalil,M Vashisth,J Irianto,J Andrechak,L Dooling,C Alvey,A Kasznel,D Chenoweth,K Yamamoto,D Discher

Journal

bioRxiv

Published Date

2021/2/8

The Development of Multivalent Nano-Self Peptides as Antagonists for Antibody-Dependent Macrophage Phagocytosis

Macrophages are immune cells that are capable of physically engulfing and clearing whole cells and particles. This process of phagocytosis is modulated by an important interaction between membrane protein CD47, present on all ‘self’cells, and the macrophage immune-receptor SIRPα. Upon binding to CD47, SIRPα delivers “do not eat me” signals to the macrophage allowing the contact cell or particle to evade engulfment. Cancer cells, which are abnormal human cells, express, and sometimes over-express CD47, which is one mechanism used to escape immune clearance. While there has been success in targeting CD47 on cancer cells in the clinic, indiscriminate binding of anti-CD47 antibodies to CD47 on healthy blood cells is unavoidable, leading to toxic side effects such as anemia. Here, we describe the design and synthesis of short, multivalent, soluble peptide (nano-Self) antagonists engineered to …

Authors

AbdelAziz R Jalil

Published Date

2020

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