Andrea Kasinski

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

 MicroRNAs (miRNAs) are small non-coding RNAs that posttranscriptionally regulate the expression of protein-coding genes. The discovery of miRNAs has resulted in a paradigm shift in our knowledge about gene control and therapeutic intervention. Through their binding to their target genes, these “master regulators” induce subtle alterations in gene expression that can culminate in major phenotypic changes. This is based on the notion that miRNAs are pleiotropic, referring to the fact that miRNAs can bind to and affect multiple targets. Although the expression of an individual miRNA target may only change marginally, the combined effect of suppressing several targets at the same time results in a phenotypic transformation. This is most clearly illustrated in the context of cancer where miRNA dysregulation contributes to many types of cancer. In some instances the combination of multiple subtle changes causes the tumor cells to become addicted to a single miRNA. MiR-21 and miR-155 are two oncogenic miRNAs (oncomiRs) that have shown this type of addictive pattern in vivo. Similarly loss of key tumor suppressive miRNAs, through epigenetic silencing, genomic loss, and reduced upstream signaling and processing, has been correlated with disease state. Based on this knowledge we have embarked on three very distinct yet equally important areas of miRNA therapeutic biology.

Project 1: Using tumor suppressive miRNAs as cancer therapeutics and sensitizers

Project 2: Restoring let-7 processing through small molecule discovery

Project 3: Identification of miRNAs that potentiate KRAS- and/or p53- driven lung tumorigenesis

Selected Publications:

Kasinski, A.L., Bader, A.G., Slack, F.J. Treating aggressive murine lung cancer with systemically delivered combinatorial miRNA therapeutics (In preperation)

*Kasinski, A.L., Slack, F.J. (2013) Generation of mouse lung epithelial cells. (Invited submission – under review) Bio-Protocols. * corresponding author Kasinski, A.L., Slack, F.J. (2012) miRNA-34 prevents cancer initiation and progression in a therapeutically resistant Kras and p53-induced mouse model of lung adenocarcinoma. Cancer Research, Sept; 72, 5576-5587

Kasinski, A.L., Slack, F.J. (2012) Arresting the culprit: targeted antagomir delivery to sequester oncogenic miR-221 in HCC.Molecular Therapy – Nucleic Acids, March; 1(3):12

Kasinski, A.L., Slack, F.J. (2011) Therapeutic microRNAs en route to the clinic: progress in validating and targeting miRNAs for cancer therapy. Nature Reviews Cancer, Nov 24; 11(12):849-64

Kim, M., Kasinski, A.L., Slack, F.J. (2011) MicroRNA therapeutics in pre-clinical cancer models. Lancet Oncology, Apr;12(4):319-321

Kasinski, A.L., Slack, F.J. (2010) Potential microRNA therapies targeting Ras, NFkB and p53 signaling.  Current Opinion in Molecular Therapeutics, Apr; 12(2):147-5

For additional laboratory information see the lab website: Kasinski Lab