Marja Nevalainen, MD, PhD
233 S. Tenth Street, Suite 309B
Philadelphia, PA 19107
(215) 503-9245 fax
Most Recent Peer-reviewed Publications
- Pharmacologic suppression of JAK1/2 by JAK1/2 inhibitor AZD1480 potently inhibits IL-6-induced experimental prostate cancer metastases formation
- Transcription factors Stat5a/b and Stat3 in prostate cancer growth and metastases
- Pharmacologic inhibition of Jak2-Stat5 signaling by Jak2 inhibitor AZD1480 potently suppresses growth of both primary and castrate-resistant prostate cancer
- STAT5A/B gene locus undergoes amplification during human prostate cancer progression
- Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy
MD, University of Turku, School of Medicine, Finland
PhD, University of Turku, Department of Cell Biology, College of Medicine, Finland
MB, University of Turku, College of Medicine, Finland
Expertise & Research Interests
Develop effective pharmacological therapies for advanced prostate cancer.
Model systems developed:
1) Dr. Nevalainen's has developed and optimized ex vivo explant organ culture system for clinical prostate cancers.
2) Her group developed and characterized a novel prostate cancer xenograft cell line and tumor system, CWR22Pc, which models castrate-resistant growth of prostate cancer.
Dr. Nevalainen's group has demonstrated that 1) Prl is locally produced by normal and malignant prostate cells, 2) prolactin (Prl) is a mitogen and survival factor for normal and malignant human and rodent prostate epithelium, 3) Stat5 is the key signaling molecule that mediates the effects of Prl in normal and malignant prostate tissue.
Dr. Nevalainen's group provided the proof-of-principle that Stat5a/b is a therapeutic target molecule in prostate cancer and further validated the concept in numerous prostate cancer model systems. Her group showed that Stat5 promotion of PCa cell growth and viability are mediated through androgen receptor (AR)-dependent and AR-independent mechanisms and, further, Stat5 effects in prostate cancer are independent of Stat3. Her group demonstrated that Stat5 promotes prostate cancer metastases processes, and nuclear Stat5 protein levels are elevated in high-grade clinical prostate cancers. Furthermore, Dr. Nevalainen's group shoed that increased nuclear Stat5 predicted early PCa recurrence.
The current focus of Dr. Nevalainen's research program is on the identification of the molecular mechanisms underlying Stat5 promotion of castrate-resistant growth of prostate cancer and testing whether Stat5 inhibition sensitizes prostate cancer cells for radiation. Dr. Nevalainen's laboratory identified a lead compound small-molecule inhibitor family for Stat5. This lead compound Stat5 inhibitor blocks Stat5 dimerization and phosphorylation of Stat5 in prostate cancer cells and blocks prostate cancer cell growth in vitro and in vivo. Importantly, the lead compound Stat5 inhibitor blocks BCR-Abl-driven Stat5 phosphorylation and growth of Imatinib-resistant chronic myeloid leukemia cells.
Members of the Research group:
Ayush Dagvadorj, MD, PhD, Research Instructor,
Zhiyong Liao, PhD, Research Associate,
Lei Gu, MD, Research Associate,
David Hoang, MD-PhD-Student (Molecular Pharmacology and Strucural Biology Program)
Pooja Talati, PhD-student (Molecular Pharmacology and Strucural Biology Program)
Elyse Amico, MS, Research Assistant,
Shauna Blackmon, Masters Student.
Mateusz Koptyra, Post-Doctoral Fellow,
Shilpa Gupta, MD, Medical Oncology Fellow,
Feng Shen, MD,
Ana Romero-Weaver, PhD,
Viviana Vogiatzi, MD, PhD,
Junaid Abdulghani, MD,
Anita Mamtani, MD,
Shyh-Han Tan, PhD,
Moogi Dagvadorj, MD,
1. Principal Investigator, RO1-Grant (5RO1CA113580-05) (2006-2017;
Stat5 in Progression of Prostate Cancer, NCI.
2. Principal Investigator: Sponsored Research Contract; Astra Zeneca.
3. Principal Investigator: Sponsored Research Contract; Novartis.
4. Co-PI: American Cancer Society Institutional Research Grant (IRG-114958), Thomas Jefferson University; Kimmel Cancer Center; (PI: Richard Pestell.
1. Principal Investigator: Research Award for Prostate Cancer Research; Stat5 as a Critical Survival Factor in Prostate Cancer, American Cancer Society, Individual Allocation from an Institutional Research Grant, IRG 97-152-11.
2. Principal Investigator: Lombardi Comprehensive Cancer Center Developmental Funds,
Jak - Stat5 Signaling in Prostate Cancer.
3. Principal Investigator, Investigator Initiated Grant; Lipid Modulation of Jak2-Stat5 Signal Transduction Pathway in Prostate Cancer,
American Institute for Cancer Research.
4. Principal Investigator, Research Scholar Grant; Androgen-Independent Growth Signaling Pathways in Prostate Cancer, American Cancer
5. Principal Investigator: New Investigator Award; Stat5 a Therapeutic Target Protein for Prostate Cancer, Department of Defense Prostate Cancer Research Program.
6. Principal Investigator: Idea Development Award; Stat3 in Metastatic Progression of Prostate Cancer, Department of Defense Prostate Cancer Research Program.
7. Principal Investigator: Idea Development Award; Interaction of Transcription Factor Stat5 with Androgen Receptor in Growth Promotion of Prostate Cancer, Department of Defense Prostate Cancer Research Program.
Training opportunities for post-doctoral fellows and students are available in our dynamic prostate cancer research laboratory. Students and fellows will receive training in a broad range of research methodologies and in writing scientific publications and grants. Studies involve in vivo and in vitro models of prostate cancer.
Successful candidates must be organized and be able to work independently. Salary is dependent on experience and follows NIH-guidelines. Highly motivated candidates are encouraged to send or email an application with a brief statement of research experience and interest and CV to: Marja Nevalainen, MD, PhD, Kimmel Cancer Center, Thomas Jefferson University Bluemle Life Science Bldg 309A, 233 S. 10th St., 19107 Philadelphia, PA. Email: email@example.com.
1) We provided the proof-of-concept that transcription factor Stat5 is a therapeutic target protein in advanced prostate cancer. 2) High levels of nuclear of Stat5a/b in primary prostate cancer predict early prostate cancer recurrence and prostate cancer specific death. High expression level of nuclear Stat5 in prostate cancer predicts poor response to radical prostatectomy. 3) We have identified a small molecule lead compound family of Stat5 inhibitors. Our Stat5 inhibitors induce extensive death of prostate cancer cells in culture, inhibit prostate xenograft tumor growth in vivo and induce death of prostate cancer epithelium in clinical prostate cancers ex vivo in explant organ cultures. 4) Our Stat5 inhibitors block transcriptional activity and phosphorylation of BCR-Abl-driven Stat5 in Imatinib sensitive and Imatinib resistant chronic myeloid leukemia cells. Our Stat5 inhibitors induce extensive apoptotic death of Imatinib-resistant BCR-Abl driven leukemia cells.
Cancer; Prostate; Stat5; Stat3; Jak2
Finnish, Swedish, German, English