Claes Wahlestedt, M.D., Ph.D.
Associate Dean for Therapeutic Innovation
Description of Research
Dr. Wahlestedt has over the past two decades attempted to merge the field of (epi-)genomics with that of drug discovery. In the decade since the first publication of the human genome in 2001, the number and general architecture of coding genes has remained remarkably stable. By contrast, surprising changes have come from noncoding regions. Several high-throughput efforts, including one spearheaded by Wahlestedt and collaborators, have provided strong evidence that, in contrast to earlier understanding, a great majority of the mammalian genome is transcribed. Wahlestedt is a frequent discussant as to the value of sequencing cancer genomes, particularly in the context of therapeutics development. In his pharmaceutical career, he initiated and participated in a number of drug discovery projects in oncology.
- Has initiated and participated in a number of drug discovery pursuits in oncology in industry as well as in academia.
- Studies epigenetic mechanisms in cancers, metastases and cancer stem cells.
- Recently developed novel cancer drug candidates (small molecules) including bromodomain inhibitors with optimized pharmacokinetic properties.
- Demonstrated, over many years, that a great majority of the mammalian genome is transcribed.
- Demonstrated that noncoding RNAs are widely expressed and can act as regulators of gene expression, for example in the context of glioblastoma.
- Demonstrated the utility of antisense oligonucleotides to up- as well as down-regulate gene expression.
- Introduced the now widespread use of locked nucleic acids in oligonucleotides.
Selected Cancer-Related Publications
- Pastori C, Peschansky VJ, Barbouth D, Mehta A, Silva JP, Wahlestedt C. Comprehensive analysis of the transcriptional landscape of the human FMR1 gene reveals two new long noncoding RNAs differentially expressed in Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome. Hum Genet :,2013 Read more »
- Wahlestedt C. Targeting long non-coding RNA to therapeutically upregulate gene expression. Nat Rev Drug Discov 12:433-46,2013 Read more »
- Clarke J, Penas C, Pastori C, Komotar RJ, Bregy A, Shah AH, Wahlestedt C, Ayad NG. Epigenetic pathways and glioblastoma treatment. Epigenetics 8:,2013 Read more »
Collaborating in the Multidisciplinary Research Program(s):