The year 2025 marked a significant period for the İTÜ Molecular Biology and Genetics Department, with several research projects receiving prestigious funding from ADEP and TÜBİTAK. These achievements highlight our growing research impact and dedication to scientific innovation. Our department’s excellence was further recognized through invitations to present at Bioinfocongress VII and the CELL-EBRITY SCIENTISTS Congress. As we look ahead to 2025, we remain committed to advancing molecular biology through high-impact research and collaboration.
Prof. Dr. Ceren Çıracı and her team receivied prestigious funding from Research Universities Support Program (ADEP) “Development of photoaccustic imaging-based photothermal therapy application for the treatment of B-cell lymphoma (FAFTET)”
Non-Hodgkin's lymphoma (NHL) is a heterogeneous group of cancers that progresses rather aggressively and its incidence has been rising rapidly in recent years, adding the global health burden. This project aims to develop a multifunctional system that combines photothermal therapy (PTT) and photoacoustic imaging (PAI) techniques by using Daudi Burkitt's lymphoma cells, an NHL model. PTT is a therapeutic strategy for the local treatment of cancer. It uses heat generated from absorbed light energy to destroy tumour cells. This method is highly specific, much less invasive and rather effective due to the intense light directed at the tumour. The effectiveness of PTT will then be evaluated by the PAI which is a biomedical imaging technique based on the photoacoustic effect. In PAI, laser pulses are delivered into biological tissue, where some of the energy is absorbed and converted into heat. This leads to transient thermoelastic expansion and wideband ultrasonic emission (i.e. megahertz-order bandwidth). These ultrasonic waves are then detected by transducers and analysed to produce images.The effectiveness of photothermal therapy will be enhanced by using gold nanoparticles to be produced in the project and cell deaths will be monitored in real time during the treatment process with photoacoustic imaging. To improve photoacoustic imaging, contrast-enhancing exogenous contrast agents in the form of nanoparticles are used to obtain better images with fewer side effects, less accumulation and visualization of only the targeted area. Nanocontrast agents are being developed for photoacoustic imaging and research is being conducted on their use for cancer diagnosis.
This project has been crafted by numerous researchers who are experts in their field. Such approach made this project a multidiciplinary project that will involve many collaborations from the departments of Electrical and Electronics, Electronics and Communication Engineering (Prof. Özgür Özdemir who is the Principal Investigator), Electrical-Electronics, Control and Automation Engineering (Assoc. Prof. Ali Fuat Ergenç), Cerrahpaşa School of Medicine (Assist. Prof. Tuğrul Elverdi), Physics Engineering (Assist. Prof. Berna Morova), and Molecular Biology and Genetics (Prof. Ceren Çıracı Muğan). By integrating knowledge and methodologies from different fields, researchers will gain a deeper and more comprehensive understanding of the cancer treatment, leading to more informed and effective solutions. Such collaborations will strengthen the applications of biotechnology in healthcare.
Assist. Prof. Dr. Abdülhalim Kılıç and his team receivied prestigious funding from Research Universities Support Program (ADEP) “Pioneering Microfluidic Platform to Mass-Produce 'Artificial Exosomes' for Targeted Cancer Therapy”
Researchers are developing a novel microfluidic platform to produce "artificial exosomes"—biomimetic nanoparticles designed for superior targeting and efficacy. By integrating a patented chip design for controlled, scalable production, the team will create next-generation functional nanocarriers for personalized therapies.
A new interdisciplinary research project aims to develop a platform for the large-scale production of "artificial exosomes," a next-generation drug delivery vehicle. While natural exosomes show great promise for targeting tumors, their clinical use is hindered by major challenges in purification and standardization. This project seeks to solve that problem by creating highly consistent, functional exosome mimetics from the ground up. The project leverages a patented, MEMS-based microfluidic platform featuring a unique micromixer design. This innovative system enables the continuous, single-step production of nanoparticles with unprecedented control over size and composition, overcoming the inefficiencies of traditional methods. These base nanoparticles are then systematically enriched with key biomolecules to precisely mimic the structure of natural exosomes.
The artificial exosomes will be engineered as "smart" therapeutic agents. They will be loaded with a range of potent anti-cancer agents, including both established chemotherapeutics and novel, project-specific compounds. Furthermore, their surfaces will be decorated with specific targeting ligands, creating a sophisticated navigation system that guides the nanoparticles to seek out and bind with cancer cells while sparing healthy tissue.
The project includes a rigorous characterization phase, where advanced analytical techniques will be employed to verify the nanoparticles' structure and confirm their therapeutic efficacy at a molecular level. This work aims to establish a powerful and scalable platform technology, paving the way for personalized nanomedicines and offering new hope for more effective and less toxic cancer treatments.
Prof. Dr. Gizem Dinler Doğanay’s new project was accepted by TUBITAK-1001 Funding Program
One of the most critical challenges in cancer treatment is the development of resistance mechanisms against therapeutic agents. Due to the complexity of signaling cascades in cancer cells, blocking a single pathway often triggers compensatory activation of alternative routes. Therefore, targeting multiple pathways or key molecular interactions has become a central focus in drug development.
Protein quality control (PQC) mechanisms, including the endoplasmic reticulum-associated degradation (ERAD) and the ubiquitin-proteasome system (UPS), are essential in eliminating misfolded proteins and maintaining cellular homeostasis. In cancer cells, increased protein synthesis and stress conditions lead to the accumulation of misfolded proteins, triggering ER stress. To survive, these cells upregulate PQC components. Among these, the AAA+ ATPase p97/VCP is a pivotal mediator in targeting unfolded proteins for degradation. Its activity is functionally connected to Bag-1S, a co-chaperone involved in PQC and apoptosis regulation.
Previous studies from the group demonstrated a direct interaction between Bag-1S and p97/VCP and identified their binding interfaces. Based on these findings, this project proposes the design of interface-specific peptides to selectively disrupt the Bag-1S:p97/VCP interaction. The goal is to modulate ERAD activity without broadly inhibiting p97/VCP, thus minimizing cytotoxicity while selectively impairing cancer cell survival.
It is aimed to synthesize these peptides, validate their interaction specificity, and assess their effects on cellular pathways, particularly ERAD, proteostasis, and survival mechanisms. By targeting a key PPI within the PQC network, this project offers a novel strategy for developing selective and effective therapeutics in breast cancer.
TÜBİTAK Supports Prof. Nevin Gül Karagüler’s Research on Antarctic Enzymes for Sustainable Biotechnology
Metagenomic approaches and protein engineering play a crucial role in the discovery and development of novel enzymes, particularly for environmentally friendly applications in green biotechnology. In this context, two novel cytochrome P450 monooxygenases belonging to the CYP102 family were recently identified from Antarctic soil samples through field-based metagenomic analysis. These enzymes were characterized by the Metagenomics and Protein Engineering Group at Istanbul Technical University (ITU), under the leadership of Prof. Dr. Nevin Gül Karagüler.
The newly identified enzymes, named CYP102A177 and CYP102M18, are cold-adapted P450s, containing a heme prosthetic group and capable of catalyzing the hydroxylation of fatty acids. Hydroxy fatty acids serve as precursors for various polymers, and thus, are highly valuable for numerous industries including pharmaceuticals, cosmetics, surfactants, and bioplastics. Due to their high catalytic efficiency at low temperatures, these cold-active enzymes stand out as attractive candidates for industrial applications requiring energy-efficient and sustainable processes, such as bioremediation, green synthesis, and drug manufacturing.
The research project entitled “Investigation of Biotechnological Potentials of Novel CYP102 Enzymes Identified by Metagenomic Approach from Antarctica” has been officially awarded funding by TÜBİTAK KUTUP-1001 Program, recognizing its scientific merit and potential impact.
Within the scope of this project, the recombinant production of CYP102A177 and CYP102M18 will be carried out, followed by enzyme purification via affinity chromatography. The characteristic Soret maxima values and enzymatic activity will be assessed through CO-binding spectral analysis. Furthermore, substrate-binding assays and LC-MS-based quantification of product conversion will be used to explore their biotechnological capabilities.
By elucidating the structure-function relationships and catalytic mechanisms of these cold-active CYP102 enzymes, the project aims to contribute significantly to green chemistry and environmentally sustainable biotechnological innovation. The work not only expands the existing enzyme toolbox for industrial biotechnology but also showcases the untapped biocatalytic potential hidden in extreme environments such as Antarctica.
Prof. Dr. Nevin Gül Karagüler Leads ADEP-Funded Project on Bioremediation Potential of Novel CYP153 Enzymes from Türkiye’s Extreme Environments
Petroleum hydrocarbon pollution remains one of the most pressing global environmental issues, posing significant threats to both ecosystems and human health. To address this problem through sustainable and innovative methods, researchers from Istanbul Technical University (ITU) have launched a new research project supported by the Research University Support Program (ADEP). This initiative is coordinated by the Council of Higher Education (YÖK) as part of Türkiye’s mission-oriented research university strategy.
The project, led by Prof. Dr. Nevin Gül Karagüler from the Department of Molecular Biology and Genetics, is entitled “Bioremediation Potential of Novel CYP153 Enzymes Identified from Türkiye’s Extreme Environments Using Metagenomics.” The study focuses on ten novel CYP153 enzymes discovered through advanced metagenomic analysis of diverse extreme habitats across Türkiye, including acidic, geothermal, and hypersaline environments.
These cytochrome P450 (CYP153) enzymes, known for their ability to catalyze alkane hydroxylation reactions, are being recombinantly produced, biochemically characterized, and tested for their efficiency in breaking down petroleum-based compounds. The enzymes are evaluated on both model n-alkanes and crude oil samples, offering insights into their real-world applicability in bioremediation efforts.
Experimental work is being carried out in close collaboration with experts from the Faculty of Chemical and Metallurgical Engineering (Department of Chemical Engineering) and the Marine Research and Technologies Research Group (DATAG) under the Climate and Life Sciences Vice Presidency of TÜBİTAK Marmara Research Center (MAM). This interdisciplinary approach enhances the project’s capacity to bridge molecular biology, chemical engineering, and marine sciences.
Supported by the ADEP program, this project explores the bioremediation potential of ten novel CYP153 enzymes identified through metagenomic analysis of Türkiye’s extreme environments. The enzymes are recombinantly produced, characterized, and tested on both model n-alkanes and crude oil. The study aims to develop innovative, sustainable biotechnological solutions to petroleum pollution using microbial enzymes adapted to harsh conditions.
The outcomes of this research are expected to contribute significantly to Türkiye’s national capacity in environmental biotechnology, potentially leading to scientific publications, patent applications, and novel industrial enzyme platforms. Ultimately, the project seeks to lay the groundwork for eco-friendly alternatives to traditional chemical remediation technologies, using naturally adapted microbial solutions to combat oil pollution more effectively and sustainably.
Prof. Dr. Gizem Dinler Doğanay, “Targeting Protein-Protein Interfaces for Cancer Therapy” Invited Speaker at Bioinfocongress VII
At Bioinfocongress VII, Prof. Dr. Gizem Dinler Doğanay presented on targeting protein-protein interactions (PPIs) as a novel approach in cancer therapy. Unlike traditional treatments that focus on enzymes or receptors, targeting PPIs addresses critical communication points between proteins that regulate cancer cell growth and survival. Disrupting these interactions offers a promising strategy to overcome drug resistance and improve therapeutic efficacy.
Prof. Dinler Doğanay discussed the structural challenges of designing molecules that can effectively interfere with PPIs, which often involve large and flat surfaces. She highlighted recent advances using small molecules, peptides, and computational tools to develop selective inhibitors. These approaches have demonstrated potential in preclinical models by modulating key signaling pathways involved in tumor progression.
The talk emphasized the importance of integrating multidisciplinary methods—including structural biology and bioinformatics—to identify and optimize PPI inhibitors. By targeting protein interaction networks rather than single proteins, this strategy aims to increase treatment specificity while minimizing side effects.
Finally, Prof. Dinler Doğanay touched on future directions, such as combining PPI inhibitors with existing therapies and exploring personalized medicine applications. Her presentation provided a concise yet comprehensive overview of the potential for PPI-targeted therapies to revolutionize cancer treatment.
Prof. Dr. Gizem Dinler Doğanay, "Protein-Protein Interactions in Cancer Signaling Pathways" Invited Speaker at CELL-EBRITY SCIENTISTS Congress
At the CELL-EBRITY SCIENTISTS Congress organized by İstinye University in 2025, Prof. Dr. Gizem Dinler Doğanay delivered a compelling presentation on the significance of protein-protein interactions (PPIs) in cancer signaling pathways. PPIs are fundamental molecular events that regulate numerous cellular processes, including those driving cancer cell survival, proliferation, and metastasis.
Prof. Dinler Doğanay emphasized that cancer progression often relies on complex networks of interacting proteins that transmit signals within and between cells. Disrupting these interactions offers a novel therapeutic avenue that can complement or overcome limitations of traditional treatments targeting individual proteins or enzymes.
During her talk, she outlined the challenges associated with targeting PPIs, such as their typically large and flat interaction surfaces, which make drug design difficult. Nevertheless, recent technological advances have enabled the development of small molecules, peptides, and biologics that can selectively inhibit key PPIs involved in oncogenic signaling.
She also highlighted examples where targeting PPIs has shown promising results in preclinical cancer models, underscoring the potential of this approach to improve treatment specificity and reduce side effects. Additionally, Prof. Dinler Doğanay discussed the integration of structural biology, computational modeling, and medicinal chemistry in accelerating the discovery of effective PPI inhibitors.
The presentation concluded with a perspective on future directions, including combining PPI-targeted therapies with conventional treatments and exploring personalized medicine approaches based on individual protein interaction profiles.
Overall, Prof. Dinler Doğanay’s talk offered valuable insights into how understanding and manipulating protein interaction networks can open new horizons in cancer therapy development.