Research

As part of the CTI research team, our scientists collaborate with colleagues in academic research and those in the pharmaceutical and biotechnology industries. We believe “it takes a village” to succeed in any therapeutic endeavor. This collaboration enhances the exchange of knowledge and expertise – enriching the learning experience.

In the CTI’s relatively short history at the university, several therapeutic projects have progressed from our labs to clinical trials. And many basic science discoveries have helped to develop novel research techniques. These successes further strengthen our resolve to uncover tomorrow’s breakthroughs and bring innovative treatments to those who need them.

The Wahlestedt laboratory is involved in these and other projects:

• Epigenetic drug discovery – We’ve designed and studied small molecule inhibitors of epigenetic modifier proteins (readers, writers, and erasers). Among these are many novel bromodomain inhibitors and HDAC inhibitors. Initially, these efforts were for cancer treatment. But more recently, some of these molecules have also been tested for brain disorders, including drug and alcohol addiction.
• Transcriptomic and RNA research – We’ve participated in many genomic and transcriptomic efforts, including serving as a core member of the FANTOM ((Functional ANnoTation Of the Mammalian genome) consortium for over two decades. Our team studies mammalian noncoding RNAs and epigenomic regulatory mechanisms, including leading the efforts on characterizing mammalian antisense (opposite strand) transcription. We developed a set of oligonucleotide tools (antagoNATs) that enable the upregulation of specific endogenous genes in vitro and in vivo.
• Oligonucleotide therapeutics – We were the first to demonstrate the efficacy and utility of antisense oligonucleotides applied directly to the brain (intracerebroventricular or intrathecal). Today, there are many clinical trials based on this approach and an approved drug (Spinraza). Our team also introduced the use of locked nucleic acids in oligonucleotides (antisense and later siRNAs).
• Alzheimer’s disease – We investigate novel therapeutic strategies to prevent and reverse Alzheimer’s disease, including exploring small molecules that modulate the activity or expression of specific epigenetic enzymes that regulate several Alzheimer’s disease targets. We are also investigating healthy aging transcriptomic (gene) signatures in the human brain. More recently, we’ve also begun to study the mechanisms contributing to sexual dimorphism in Alzheimer’s disease and the metabolic contributions to this disorder. We collaborate with biotechnology companies and nonprofit organizations to bring promising treatments to the clinic as quickly as possible.
• Cancer – Our primary focus is discovering novel drug targets and developing and testing small molecule inhibitors targeting epigenetic modifiers, particularly inhibitors of histone deacetylases (HDACs) and bromodomain and extraterminal domain (BET) proteins. These treatments are being evaluated in a wide array of liquid and solid malignancies.
• Personalized medicine – As we continue to build our understanding of diseases’ underlying processes, we can discover better treatments – personalized approaches designed to meet each person’s needs. Recently, we’ve developed an ex vivo drug sensitivity testing (DST) approach, which uses a patient’s cancer cells, to help create customized treatment plans. The DST screen, which can be performed rapidly (offers results within 21 days), can help suggest treatment options with high cancer specificity and low normal tissue toxicity. This, sometimes combined with genetic information, can offer patient-specific treatment options patients don’t usually receive as part of the standard clinical practice.

You can find a complete list of published work from the Wahlestedt laboratory (over 300 peer-reviewed publications) in my online bibliography (over 42,000 scientific citations).