Wessam Melik

About Wessam Melik

Career Overview
Dr. Melik defended his PhD thesis in the major molecular genetics, “Molecular characterization of the Tick-borne encephalitis virus; Environments and replication” in 2012, Stockholm University, Sweden.

Subsequently, Dr. Melik followed a postdoctoral training in Dr. Marshall Bloom’s laboratory at the National Institute of Allergy and Infectious Diseases (NIAID) NIH in Montana, USA. This experience further increased his passion for virology, exploring host responses to viral infections, and the field of immunology.

After completing his postdoctoral studies, Dr. Melik returned to Sweden and joined Örebro University in 2015 to conduct research on edible vaccines by producing virus-like particles in plants.

In 2016, Dr. Melik was appointed the role of leading the "Unit of Microbiology, Immunology, and Reproductive Sciences" at the School of Medical Sciences and in 2021, he was granted a position as associate professor (Docent) at Örebro University, School of Medical Sciences.

Dr. Melik has a strong disposition towards teaching, which he actively engages in through teaching at the medical program and master's program at Örebro University. Beyond academia, Dr. Melik has a profound passion for visiting high schools to describe fundamental research and explain the simple mechanisms of biology and virology. This outreach serves as a means for Dr. Melik to spark interest and curiosity among young students.

Background on previous and ongoing research
During his studies, Dr. Melik established the development of various flavivirus subgenomic replicon systems, including the Swedish Torö strain and the indigenous North American TBEV Powassan Virus (POWV). These replicons have been used in numerous research works and have been shared with scientific communities globally.

Research activities comprehend investigations into the impact of antiviral agents on viral replication, the interplay between virus-host proteins that regulate, signaling pathways like MAP-Kinase, JAK-STAT, and neurite outgrowth. By depleting specific host factors, researchers could scrutinize the effects on virus replication or neurite morphology, shedding light on potential cognitive impairments associated with encephalitis caused by TBEV. Dr. Melik has also studied the transcriptome regulation (RNA expression) in TBEV-infected tick cells (ISE6).

He also developed the interest regarding quantitative functional approaches to explore fundamental and translational questions related to the structure of flaviviruses, their interactions with cells, and humoral immunity. These perspectives are used to guide the development of vaccines, and techniques for the evaluation of innate and humoral immunity.

Vaccin research
Dr. Melik is actively involved in a project aimed at developing new vaccines and enhancing knowledge on administering vaccines directly on the body's mucous membranes. This initiative, funded by the Knowledge Foundation's Synergy program in collaboration with ten companies, focuses on advancing vaccination methods. Dr. Melik plays a key role as a co-applicant, contributing to the project's development and engagement with the Knowledge Foundation. The project aims to consolidate expertise in vaccinology at Örebro University, promoting partnerships between academia, industry, and the community. The project, Developvaccines@oru, targets critical gaps in vaccination by exploring innovative approaches in composition and formulation, production, and vaccination techniques. Dr. Melik leads subproject 3, focusing on Vaccination and evaluation.

Antiviral research
The research focuses on investigating the antiviral properties of plantaricins, specifically Plantaricin NC8 αβ, against enveloped viruses like flaviviruses, coronaviruses, influenza viruses, and HIV. Plantaricins are hypothesized to target the negatively charged phospholipids in viral membranes, potentially exerting direct antiviral effects against enveloped viruses. The study aims to elucidate the mechanisms by which plantaricins interact with viral envelopes and their potential immunomodulatory effects. Notably, Plantaricin NC8 αβ has shown efficient antiviral activity against flaviviruses like Langat and Kunjin, coronavirus SARS-CoV-2, influenza A virus (IAV), and HIV-1. The research involves testing various plantaricins in vitro and in vivo to understand their antiviral effects and underlying mechanisms. The goal is to develop novel broad-spectrum antiviral agents that can target viral envelopes efficiently and safely, potentially offering new strategies for combating viral infections.

Research interest
Mechanisms of Blood-Brain Barrier Disruption and Viral Invasion of the Central Nervous System.
Flaviviruses, including tick-borne flaviviruses (TBFV), employ various mechanisms to invade the central nervous system (CNS) and cause neuropathogenesis. These viruses can breach the blood-brain barrier (BBB) through different pathways, such as upregulating tight junction degrading proteins, toll-like receptor 3 (TLR3) stimulation, or axonal transport. Once in the CNS, flaviviruses induce neurological symptoms through direct cell lysis, cell cycle blockage, apoptosis, and immune-induced pathologies. Studies highlight the role of proteins like NS1, MMP-9, and proinflammatory cytokines in disrupting the BBB. The endosomal sorting complex required for transport (ESCRT) machinery is crucial for maintaining brain endothelial cell polarity and facilitating virus invasion by releasing enveloped viruses from host cells. Additionally, subgenomic flavivirus RNA (sfRNA) plays a vital role in viral pathogenesis by promoting viral replication and neuroinvasion. Understanding these mechanisms is essential for developing targeted therapies to mitigate neurological damage caused by flavivirus infections and improve patient outcomes.

Screening and combating "don't eat me" CD47 ligands in cancer cells.
The study aims to identify metabolites in the CD47 signaling pathway that inhibit CD47 biosynthesis in cancer cells. We aim to use an in-house expression system, Reporter virus particles (RVPs), to infect cancer cells and express the inhibitory molecule. The goal also involves screening and identifying additional 'don't eat me' signals like CD47 with its complementary receptor on macrophages.