Senturk Lab.

Molecular Carcinogenesis and Functional Genomics

OVERVIEW

Translational research is an interdisciplinary branch of the biomedical field which aims to facilitate the application of fundamental discoveries of basic science into medical practices in order to enhance human health and well-being. Translational research implements a “bench-to-bedside” vision, harnessing the knowledge of basic science and preclinical studies with the ultimate goal to develop promising novel therapeutics and treatment options that can be used clinically and are able to be commercialized. Today, molecular alterations associated with different diseases are being deciphered by basic research studies, leading to translational research-supported discovery of new therapeutic agents designed to counteract or actually reverse such alterations. As a centre of excellence laboratory for basic and translational cancer research, we aim to provide an ideal environment with state-of-the-art platforms for target discovery and the development of targeted therapies for the treatment of cancer. Our ambition is to advance knowledge and innovation with the future goal to deliver preclinical drug candidate molecules for progression into the clinic.

RESEARCH INTERESTS

Our lab is aiming to establish a translational research niche fostered by biological discovery activities of basic research. In this context, we are interested in three linked, broad and long-term themes: (i) identifying and validating novel “druggable” cellular targets across cancer types, (ii) discovering and developing innovative biological drugs (mainly, but not limited to, therapeutic monoclonal antibodies, mAbs) against such targets in the field of oncology by focusing on anti-proliferative and immunotherapy mechanisms and (iii) developing and producing “biosimilar” and “bio better” versions of already approved original biological medicines. In order to do so, our lab is interested in developing the most comprehensive and relevant models for the examination of biological pathways and disease pathobiology.

  1. Future drug targets are expected to emerge from high-throughput functional genomics screening technologies supported by genetic engineering tools and analysis approaches that identify the mechanisms regulating biological processes. Therefore, our lab is interested in utilizing RNAi and CRISPR/Cas9 technology in-vitro and in vivo as the “discovery engine” of genome-wide screening libraries to uncover cancer-specific vulnerabilities. Here, we are going to perform pooled screens using lentivirus-based mechanisms for sgRNA delivery and Cas9 expression as well as shRNA expression.
  2. Conventional production of monoclonal antibodies involves in vitro and in vivo procedures. Here, potentially druggable molecule identification will be followed by immunogen production and mouse immunization, hence mAb development in antibody-producing B cells. These B lymphocytes will then be fused with myeloma fusion partners to generate immortalized hybrid somatic cells, a hybridoma cell line capable of producing high-quality antibodies. Systematic screening and characterization of therapeutic mAbs-secreting hybridomas will be performed for their capability to block the activity of target molecules/pathways and hence the proliferation of cancer cells. Candidate molecules will be humanized by the replacement of mouse constant and V framework regions for human sequences and expression of these constructs in mammalian cell cultures.
  3. Biologics are today’s most important therapeutic agents and valuable life-saving medicines with profound impact on many medical fields primarily oncology, but also cardiology, neurology, immunology and others. They are manufactured in and extracted from genetically engineered living systems through the use of biotechnology, such as recombinant DNA technology, controlled gene expression, or antibody technologies. A similar biologic or biosimilar drug, much like generic drugs, is a less costly version of an originator biological product. Yet, biosimilars meet extremely high standards for quality, safety, efficacy, and comparability or similarity to the reference biologic and can only be manufactured when the original product’s patent expires. In this context, our lab is interested in developing biosimilar versions of original biologics which is a robust process that requires science-based and data-intensive steps in order to ensure that there is no clinically meaningful difference between the biosimilar and the reference product.
RESEARCH HIGHLIGHTS

We undertake a wide range of significant research fields focused on the following major areas of investigation: (1) identification and characterization of the mechanisms driving cancer; (2) druggable target identification and validation against such mechanisms. The close proximity to basic and translational research expertise for interdisciplinary collaboration is invaluable in the selection and validation of novel cancer drug discovery targets. Our lab is at the center of characterization of cancer-specific vulnerabilities using high-throughput data combined with information on genomic abnormalities in order to increase research opportunities and support improved treatment of such diseases.