Luisa Di Paola

Università Campus Bio-Medico di Roma, Faculty of Engineering, Faculty Member

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Dr. Di Paola got her doctorate in Chemical Industrial Processes at the University Roma “La Sapienza”. She collaborated, during her doctorate, with prof. JM Prausnitz and H. Blanch at the University of California at Berkeley. Currently she is Assistant Professor at the University Campus Biomedico in Rome. Her research interests span from bioinformatics to biotechnological processes. She’s author of 57 papers on international journals and books. She’s Editor-in-chief of the "International Journal of Biochemistry Research

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Papers by Luisa Di Paola

Symmetric versus Asymmetric Features of Homologous Homodimeric Amine Oxidases: When Water and Cavities Make the Difference

Symmetry

Symmetry is an intrinsic property of homo-oligomers. Amine oxidases are multidomain homodimeric e... more Symmetry is an intrinsic property of homo-oligomers. Amine oxidases are multidomain homodimeric enzymes that contain one catalytic site per subunit, and that share a high homology degree. In this paper, we investigated, by fluorescence spectroscopy measurements, the conformational dynamics and resiliency in solutions of two amine oxidases, one from lentil seedlings, and one from Euphorbia characias latex, of which the crystallographic structure is still unknown. The data demonstrate that slight but significant differences exist at the level of the local tridimensional structure, which arise from the presence of large internal cavities, which are characterized by different hydration extents. Molecular dynamics and a contact network methodology were also used to further explore, in silico, the structural features of the two proteins. The analysis demonstrates that the two proteins show similar long-range symmetrical connectivities, but that they differ in their local (intra-subunit) c...

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A (2014) GIANT: a cytoscape plugin for modular networks. PLoS One 9: e105001. doi: 10.1371/journal.pone.0105001 PMID: 25275465

Network analysis provides deep insight into real complex systems. Revealing the link between topo... more Network analysis provides deep insight into real complex systems. Revealing the link between topological and functional role of network elements can be crucial to understand the mechanisms underlying the system. Here we propose a Cytoscape plugin (GIANT) to perform network clustering and characterize nodes at the light of a modified Guimerà-Amaral cartography. This approach results into a vivid picture of the a topological/functional relationship at both local and global level. The plugin has been already approved and uploaded on the Cytoscape APP store.

Disclosing Through Protein Contact Networks

Methods in Molecular Biology

Proteins are located in the twilight zone between chemistry and biology, where a peculiar kind of... more Proteins are located in the twilight zone between chemistry and biology, where a peculiar kind of complexity starts. Proteins are the smallest 'devices' showing a sensible adaptation to their environment by the production of appropriate behavior when facing a specific stimulus. This fact qualifies (from the 'effector' side) proteins as nanomachines working as catalysts, motors, or switches. However (from the sensor side), the need to single out the 'specific stimulus' out of thermal noise qualifies proteins as information processing devices. Allostery corresponds to the modification of the configuration (in a broad sense) of the protein molecule in response to a specific stimulus in a non-strictly local way, thereby connecting the sensor and effector sides of the nanomachine. This is why the 'disclosing' of allostery phenomenon is at the very heart of protein function; in this chapter, we will demonstrate how a network-based representation of protein structure in terms of nodes (aminoacid residues) and edges (effective contacts between residues) is the natural language for getting rid of allosteric phenomena and, more in general, of protein structure/function relationships.

Polymorphism on human aromatase affects protein dynamics and substrate binding: spectroscopic evidence

Biology Direct

Human aromatase is a member of the cytochrome P450 superfamily, involved in steroid hormones bios... more Human aromatase is a member of the cytochrome P450 superfamily, involved in steroid hormones biosynthesis. In particular, it converts androgen into estrogens being therefore responsible for the correct sex steroids balance. Due to its capacity in producing estrogens it has also been considered as a promising target for breast cancer therapy. Two single-nucleotide polymorphisms (R264C and R264H) have been shown to alter aromatase activity and they have been associated to an increased or decreased risk for estrogen-dependent pathologies. Here, the effect of these mutations on the protein dynamics is investigated by UV/FTIR and time resolved fluorescence spectroscopy. H/D exchange rates were measured by FTIR for the three proteins in the ligand-free, substrate- and inhibitor-bound forms and the data indicate that the wild-type enzyme undergoes a conformational change leading to a more compact tertiary structure upon substrate or inhibitor binding. Indeed, the H/D exchange rates are dec...

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Artificial kidney: A chemical engineering challenge

The growing demand for renal replacement is boosting the development of artificial kidney devices... more The growing demand for renal replacement is boosting the development of artificial kidney devices. Since its birth in the early 20th century, the artificial kidney has represented the cutting edge of biomedical engineering, with the continuous development of high-performance devices. Actually, around two million patients are regularly treated with renal replacement therapy, but the number is expected to grow steeply in the near future due to the increasing average age of the population in OCSE countries and with accessibility to therapy growing for patients in developing countries. This Chapter presents a survey of current state-of-art devices, after a historical perspective, with a perspective to future developments, regarding bioartificial implantable devices, for a definitive, complete replacement of renal function. The main focus of this chapter is to highlight the great role membrane science and chemical engineering play in the development of innovative technologies in the fiel...

Toward an Efficient Biorefining of Microalgae and Biomass Alike: a Unit Operating View on How to Mimick the Optimisation History of the Crude Oil Refining Industry

One major hindrance to biomass deployment, and one which only benefitted from an unbalanced devel... more One major hindrance to biomass deployment, and one which only benefitted from an unbalanced development, is refining into the different fractions which have a market value. Indeed, most products obtained from oil refining owe to the level of sophistication and optimisation reached by energy-integrated fractioning (mostly, distillation) networks. The separation stage of microalgal and lignocellulosic biomass could be addressed by using a converging approach employing a multipurpose solvent which may be adapted by one single and simple operation to different extractions. Such a single-solvent separation approach would lend itself to scaleup to a solvent-integrated fractionation network that might help mimicking the success story of the oil refining industry.

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Cardiovascular Active Peptides of Marine Origin with ACE Inhibitory Activities: Potential Role as Anti-Hypertensive Drugs and in Prevention of SARS-CoV-2 Infection

International Journal of Molecular Sciences

Growing interest in hypertension—one of the main factors characterizing the cardiometabolic syndr... more Growing interest in hypertension—one of the main factors characterizing the cardiometabolic syndrome (CMS)—and anti-hypertensive drugs raised from the emergence of a new coronavirus, SARS-CoV-2, responsible for the COVID19 pandemic. The virus SARS-CoV-2 employs the Angiotensin-converting enzyme 2 (ACE2), a component of the RAAS (Renin-Angiotensin-Aldosterone System) system, as a receptor for entry into the cells. Several classes of synthetic drugs are available for hypertension, rarely associated with severe or mild adverse effects. New natural compounds, such as peptides, might be useful to treat some hypertensive patients. The main feature of ACE inhibitory peptides is the location of the hydrophobic residue, usually Proline, at the C-terminus. Some already known bioactive peptides derived from marine resources have potential ACE inhibitory activity and can be considered therapeutic agents to treat hypertension. Peptides isolated from marine vertebrates, invertebrates, seaweeds, o...

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The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach

Journal of Proteome Research

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Novel indole derivatives targeting HuR-mRNA complex to counteract high glucose damage in retinal endothelial cells

Biochemical Pharmacology

The ELAVL1 (or human antigen R - HuR) RNA binding protein stabilizes the mRNA, with an AU-rich el... more The ELAVL1 (or human antigen R - HuR) RNA binding protein stabilizes the mRNA, with an AU-rich element, of several genes such as growth factors (i.e. VEGF) and inflammatory cytokines (i.e. TNFα). We hereby carried out a virtual screening campaign in order to identify and test novel HuR-mRNA disruptors. Best-scored compounds were tested in an in-vitro model of diabetic retinopathy, namely human retinal endothelial cells (HRECs) challenged with high-glucose levels (25 mM). HuR, VEGF and TNFα protein contents were evaluated by western-blot analysis in total cell lysates. VEGF and TNFα released from HRECs were measured in cell medium by ELISA. We found that two derivatives bearing indole moiety, VP12/14 and VP12/110, modulated HuR expression and decrease VEGF and TNF-α release from HREC exposed to high glucose (HG) levels. VP12/14 and VP12/110 inhibited VEGF and TNF-α release in HRECs challenged with high glucose levels, similarly to dihydrotanshinone (DHTS), a small molecule known to interfere with HuR- TNFα mRNA binding. The present findings demonstrated that VP12/14 and VP12/110 are innovative molecules with anti-inflammatory and anti-angiogenic properties, suggesting their potential use as novel candidates for treatment of diabetic retinopathy.

Design of microfluidic bioreactors: Transport regimes

Asia-Pacific Journal of Chemical Engineering

Characterization of innovative sensors for volatile organic compounds trace compounds in biogas

Asia-Pacific Journal of Chemical Engineering

P2X7 receptor antagonism: Implications in diabetic retinopathy

Biochemical Pharmacology

Diabetic retinopathy (DR) is the most frequent complication of diabetes and one of leading causes... more Diabetic retinopathy (DR) is the most frequent complication of diabetes and one of leading causes of blindness worldwide. Early phases of DR are characterized by retinal pericyte loss mainly related to concurrent inflammatory process. Recently, an important link between P2X7 receptor (P2X7R) and inflammation has been demonstrated indicating this receptor as potential pharmacological target in DR. Here we first carried out an in silico molecular modeling study in order to characterize the allosteric pocket in P2X7R, and identify a suitable P2X7R antagonist through molecular docking. JNJ47965567 was identified as the hit compound in docking calculations, as well as for its absorption, distribution, metabolism and excretion (ADME) profile. As an in vitro model of early diabetic retinopathy, human retinal pericytes were exposed to high glucose (25mM, 48h) that caused a significant (p&amp;amp;lt;0.05) release of IL-1β and LDH. The block of P2X7R by JNJ47965567 significantly (p&amp;amp;lt;0.05) reverted the damage elicited by high glucose, detected as IL-1β and LDH release. Overall, our findings suggest that the P2X7R represents an attractive pharmacological target to manage the early phase of diabetic retinopathy, and the compound JNJ47965567 is a good template to discover other P2X7R selective antagonists.

Are Proteins Just Coiled Cords? Local and Global Analysis of Contact Maps Reveals the Backbone-Dependent Nature of Proteins

Current Protein & Peptide Science, 2015

In this work, we present an extensive analysis of protein contact network topology applied to a w... more In this work, we present an extensive analysis of protein contact network topology applied to a wide data set. We extended the concept of degree distribution to graphlets, describing local connectivity patterns. We compared results to those derived from artificial networks of the same size (number of nodes), reproducing the average degree of each protein network. The artificial networks resemble the coiling of immaterial cords and we tried to understand if they could catch the protein structure topology upon the sole constraint of backbone (cord). We found a surprisingly similar pattern for local topological descriptors (graphlets distribution) while real proteins and cords differ at large extent in the global topological invariant average shortest path that presumably catches the systemic nature of protein and the non negligible encumbrance of backbone (residues steric hindrance). We demonstrated average shortest path to link polymer length and physical size of the molecule, and its minimization plays the role of `target function` of folding process.

Exploring the stability of dimers through protein structure topology

Current Protein & Peptide Science, 2015

Protein homodimers pose some intriguing questions about the relation between structure and stabil... more Protein homodimers pose some intriguing questions about the relation between structure and stability. We approached the problem by means of a topological methodology based on protein contact networks. We correlated local interface descriptors with structure and energy global properties of the systems under analysis. We demonstrated that the graph energy, formerly applied to the analysis of unconjugated hydrocarbons structures, is the bridge between the topological and energetic description of protein complexes. This is a first step for the generation of a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;protein structural formula&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, analogous to the molecular graphs in organic chemistry.

Adsorbimento di bilirubina su resine polimeriche

Reologia di soluzione acquose acido ialuronico - albumina

Pacietal2012

Characterization of Protein–Protein Interfaces, Considering Surface-Roughness and Local Shape

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Comment-Protein Contact Networks: A New Framework for Structural Biology

Protein structure information is not sufficient to predict biological functionality. Among differ... more Protein structure information is not sufficient to predict biological functionality. Among different approach of analysis, protein contact networks provide a previliged point of view through the recognition of proteins as complex networks: the invariant of the networks are related to different properties of protein molecules. Folding dynamics and allosteric binding find new and detailed description within this framework, pointing at this methodology as one of the most promising in the perspective of big data analysis of whole proteomes.