Past Research:
Ongoing Work:
Industrial Relevance:
Dr. Nevalainen's research accomplishments include the development and optimization of a long-term 3D
organ culture system under serum-free conditions for normal and malignant rodent and human prostate
tissue. She has demonstrated that 1) prolactin (Prl) is a mitogen and survival factor for normal and
malignant human and rodent prostate epithelium, 2) Prl is locally produced by normal and malignant
prostate cells, 3) Stat5 is the key signaling molecule that mediates the effects of Prl in normal and
malignant prostate tissue, and 4) that Stat5 is a crucial survival protein for prostate cancer cells.
Dr. Nevalainen's research program focuses on identifying protein kinase signaling
pathways that mediate survival of castration-resistant and metastatic prostate cancer cells,
with special focus on Stat transcription factors. Dr. Nevalainen's laboratory has shown that
activation Stat5 is critical for the viability of human prostate cancer cells in culture and
for prostate cancer xenograft tumor growth in nude mice. Moreover, Dr. Nevalainen has shown
that activation of Stat5 in clinical prostate cancers is clustered to cancers of high
histological grade and Stat5 activation in primary prostate cancer predicts early disease
recurrence. Recent work demonstrated that the Stat5 signaling pathway synergizes with androgen
receptor signaling in prostate cancer cells. The current focus of Dr. Nevalainen's research
program is on the identification of the molecular mechanisms by which Stat5 contributes to
castration-resistant growth of prostate cancer, the individual roles of Stat5a vs. Stat5b as
survival factors for prostate cancer cells, and on testing whether Stat5 inhibition sensitizes
prostate cancer cells for radiation. Recently, Dr. Nevalainen's laboratory identified a lead
compound small-molecule inhibitor of Stat5a/b. Dr. Nevalainen aims to use the Jak-Stat5 pathway
as a molecular target to develop novel pharmaceutical strategies for prostate cancer therapy.
1) We have established transcription factor Stat5 as a molecular target for therapy development for
prostate cancer. Inhibition of Stat5a/b can be achieved by antisense oligonucleotides, RNA interference
of by development of small-molecule Stat5 inhibitors. 2) Our data indicate that Stat5 is particularly
active in high grade prostate cancer and in castration-resistant and metastatic disease which suggests
that Stat5 may be specifically powerful in targeting advanced prostate cancer. 3) We have shown that
activation of Stat5a/b in primary prostate cancer predicts early prostate cancer recurrence. This
knowledge can be used to design a prognostic assay to guide the selection of treatment for prostate
cancers of intermediate Gleason grades.