prof. Matthias D'hooghe (PhD)

Multiple myeloma (MM) is a deadly haematological cancer, characterized by the accumulation of abnormal plasma cells in the bone marrow. Despite the substantial progress in MM treatment, the vast majority of MM patients eventually relapse. On top of that, current treatments go along with severe side effects, underlining the need for new therapeutics that work via a novel mode of action. Therefore, our (chemistry-oriented) research group SynBioC aims at developing novel therapeutic strategies against MM, following a multi-target approach, in collaboration with the lab of Prof. K. De Bosscher (Faculty of Medicine, UGent).
In the first approach, we develop novel inhibitors for the HDAC6 enzyme, a member of the histone deacetylase family which consists of 18 isozymes and mediate the removal of acetyl groups from lysine residues. HDAC inhibitors can act on 11 HDAC isozymes, but isoform-selective inhibition is important with respect to clinical efficacy. In particular, HDAC6 has been identified as a relevant target because of its unique features: it is located in the cytoplasm, has two catalytic domains and a ubiquitin-binding domain and mediates, amongst other cellular processes, the trafficking of ubiquitinated misfolded proteins to the aggresome/autophagy pathway. Therefore, this isozyme is an important target to combat MM when combined with proteasome inhibitors (PIs), as this strategy would allow overcoming resistance to PIs. The second approach is situated on the nuclear receptor level. Synthetic glucocorticoids (GCs), such as dexamethasone and prednisolone, bind to the glucocorticoid receptor (GR) and induce apoptosis of MM cells. GCs are administered in all stages of MM treatment, but evoke adverse side effects and are subject to a rising resistance. Therefore, we aim to improve glucocorticoid efficacy and circumvent therapy resistance through exploitation of a recently discovered alternative mode of action involving the glucocorticoid receptor (GR).
Other cancer-related research projects in our group concern the development and assessment of new curcumin-based structures, in collaboration with Prof. J. Van Camp (Faculty of Bioscience Engineering, UGent). Although curcumin has amply shown to inhibit cancer cell proliferation, this molecule has also been described to possess a low bioavailability, which is related to poor absorption. Moreover, curcumin is rapidly metabolized and systemically eliminated from the body, suffers from chemical degradation in aqueous solutions, and shows rather unspecific activity across a range of assays. These drawbacks imply a serious concern and hamper potential applications of curcumin-like compounds in health care, pointing to the need for new, preferably three-dimensional entities starting from the curcumin mother structure, of course without compromising its pronounced biological activities
 

Matthias D’hooghe was born in Kortrijk, Belgium, in 1978. He received his Master’s diploma in 2001 (Master of Science in Bioscience Engineering: Chemistry) and his PhD degree in 2006 (Doctor in Applied Biological Sciences: Chemistry), both from Ghent University, Belgium, with Prof. N. De Kimpe as promoter. In 2007, he became post-doctoral assistant at the Department of Green Chemistry and Technology, Ghent University, and in 2009 he performed a short postdoctoral stay with Prof. D. Vogt at Eindhoven University of Technology (The Netherlands) in the field of homogeneous catalysis. In October 2010, he was promoted to Professor (Research Professor) at the Department of Green Chemistry and Technology (Faculty of Bioscience Engineering, Ghent University), and he was granted tenure in 2015. His main research interests include the chemistry of small-ring azaheterocycles, with a special focus on aziridines, azetidines and b-lactams, and the synthesis of different classes of bioactive heterocyclic compounds at the SynBioC Research Group.
Prof. D’hooghe is the author of 170 publications in international journals (H-index 31) and was elected as a laureate of the DSM Science & Technology Awards 2007, finalist of the European Young Chemist Award 2012 and recipient of the Thieme Chemistry Journal Award 2013. He organized and chaired the international Bioheterocycles 2019 conference and became a Bioheterocycles International Scientific Committee member in June 2019.
 

• prof. Matthias D'hooghe (PhD) - principal investigator, associate professor
• Katarina Magdalenic - doctoral fellow
• Julie De Munck - doctoral fellow
• Ulrike Ronse - doctoral fellow
   

• “The zinc-binding group effect: lessons from non-hydroxamic acid vorinostat analogs” J. Med. Chem. 2023, 66, 7698-7729.
• “Identification of mercaptoacetamide-based HDAC6 inhibitors via a lean inhibitor strategy: screening, synthesis, and biological evaluation” Chem. Commun. 2022, 58, 6239-6242.
• “Selective pharmacological inhibitors of HDAC6 reveal biochemical activity but functional tolerance in cancer models” Int. J. Cancer 2019, 145, 735-747.
• “Synthesis of 1,4-thiazepane-based curcuminoids with promising anticancer activity” Chem. Eur. J. 2019, 25, 12583-12600.
• “Synthesis of potent and selective HDAC6 inhibitors bearing a cyclohexane- or cycloheptane-annulated 1,5-benzothiazepine scaffold” Chem. Eur. J. 2017, 23, 128-136.
   

• Faculty of Bioscience Engineering, SynBioC Research, Group (BW11), Coupure Links 653, 9000 Gent
• SynBioC Research Group