University Home | Hospital | Pulse Employment | Contact Us | Search | News 
Thomas Jefferson University Search Jefferson
Jefferson Medical College Jefferson College of Graduate Studies Jefferson College of Health Professions
Menu

Thomas Jefferson University - Marja Nevalainen, M.D., Ph.D.
Marja Nevalainen, M.D., Ph.D.

Cancer Biology
Kimmel Cancer Center
Thomas Jefferson University
Jefferson Medical College
Department of Cancer Biology
Department of Medical Oncology
Department of Urology
Associate Professor
Appointed: 2006
Mailing Address
Dept. of Cancer Biology, BLSB 309A, 233 S. 10th St.
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: 215-503-9250
Fax: 215-503-9245
Marja.Nevalainen@jefferson.edu
Qualifications
MD
PhD
Expertise and Research Interests
Mission:
To identify new therapeutic target proteins for castration-resistant and metastatic prostate cancer.

Past Research:
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)Stat5 is a crucial survival protein for prostate cancer cells.

Ongoing Work:
Dr. Nevalainen's research program focuses on identifying protein kinase signaling pathways that mediate survival of castration-resistant and metastatic prostate cancer cells, with a special focus on Stat transcription factors. Dr. Nevalainen's laboratory has shown that Stat5 is critical for the viability of human prostate cancer cells in culture and for prostate xenograft tumor growth in nude mice. Moreover, Dr. Nevalainen has shown that activation of Stat5 in primary prostate cancer predicts early disease recurrence. 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, on testing whether Stat5 inhibition sensitizes prostate cancer cells for radiation, and whether acetylation of Stat5a/b contributes to transcriptional activity of Stat5 in prostate cancer cells. Recently, Dr. Nevalainen's laboratory identified small-molecule inhibitors for Stat5. Dr. Nevalainen aims to use the Jak-Stat5 pathway as a molecular target to develop novel pharmaceutical strategies for prostate cancer therapy.

Lab members:
Ayush Dagvadorj, MD, PhD, Research Associate,
Zhiyong Liao, PhD, Research Associate,
Lei Gu, MD, Research Associate,
Paraskevi Viviana Vogiatzi, MD, PhD, Post-Doctoral Fellow,
Mateusz Koptyra, Post-Doctoral Fellow,
Andrzej Wojcieszynski, Medical Student,
Anita Mam, Medical Student,
Shilpa Gupta, MD, Medical Oncology Fellow,
Jacqueline Lutz, MS, Research Assistant.

Support:
Ongoing support:
1. Principal Investigator, RO1-Grant (RCA11358A);
Stat5 in Progression of Prostate Cancer, NCI, TCB.

2. Principal Investigator: Idea Development Award; Stat3 in Metastatic Progression of Prostate Cancer, Department of Defense Prostate Cancer Research Program (2006-2009).

3. 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 (2007-2010).

4. Principal Investigator: Sponsored Research Contract; Therapeutic Targeting of Stat5 and Stat3 in Human Prostate Cancer by AZD1480 (2009-2011), Astra Zeneca.

5. Co-PI: American Cancer Society Institutional Research Grant (IRG-114958), Thomas Jefferson University; Kimmel Cancer Center; (PI: Richard Pestell), (2008-2011).


Completed Support:
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, (01.01.04 - 12.31.04).

2. Principal Investigator: Lombardi Comprehensive Cancer Center Developmental Funds,
Jak - Stat5 Signaling in Prostate Cancer; (10.01.04).

3. Principal Investigator, Investigator Initiated Grant; Lipid Modulation of Jak2-Stat5 Signal Transduction Pathway in Prostate Cancer,
American Institute for Cancer Research (04.01.04 - 03.31.07).

4. Principal Investigator, Research Scholar Grant; Androgen-Independent Growth Signaling Pathways in Prostate Cancer, American Cancer
Society (07.01.04 - 06.31.09).

5. Principal Investigator: New Investigator Award; Stat5 a Therapeutic Target Protein for Prostate Cancer, Department of Defense Prostate Cancer Research Program (12.01.04-11.30.08).

Training Opportunities:
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: marja.nevalainen@jefferson.edu.

Industrial Relevance
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, or by development of small-molecule Stat5 inhibitors. 2)Stat5 is particularly active in high grade prostate cancer and in castration-resistant disease, which suggests that Stat5 may be specific therapeutic target for advanced prostate cancer. 3) 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 scores. 4) Long-term expertise and experience in 3D-Ex vivo prostate cancer organ culture system for drug screening. 5) A new androgen-regulated and tumorigenic human prostate cancer cell line established in our lab. 6)Characterization of a small-molecule lead compound for pharmacological inhibition of Stat5a/b.
Keywords
Cancer; Prostate; Breast; Stat5; Jak2
Publications
  • 1. Nevalainen MT, Valve EM, Mäkelä SI, Bläuer M, Tuohimaa PJ, Härkönen PL. Estrogen and prolactin regulation of rat dorsal and lateral prostate in organ culture. Endocrinology, 129:612-622, 1991.

  • 2. Väänänen HK, Valve EM, Mäkelä SI, Nevalainen MT, Härkönen PL. Hormone regulation of carbonic anhydrase II expression. In: Carbonic Anhydrase: from Biochemistry and genetics to Physiology and Clinical Chemistry, Botre, G. Frass, B.T. Storey (eds), VCH Verlagsgesellchaft, Weinheim, Germany 1991, pp 345-351.

  • 3. Martikainen P, Nevalainen M, Härkönen P. Organ cultures of rat and human prostate, In: Techniques in reproductive biomedicine. A method manual. Anand Kumar (ed), B.I. Churchill Livingstone, pp 666-680, 1993.

  • 4. Nevalainen MT, Härkönen PL, Valve EM, Ping W, Nurmi M, Martikainen PM. Hormone regulation of human prostate in organ culture. Cancer Research 53:5199-5207, 1993.

  • 5. Nevalainen MT, Valve EM, Ingleton P, Härkönen PL. Expression and hormone regulation of prolactin receptor in rat dorsal and lateral prostate. Endocrinology 137: 3078-3088, 1996.

  • 6. Nevalainen MT, Valve EM, Ingleton PM, Martikainen P, Nurmi M, Härkönen PL. Prolactin receptors are expressed and functioning in human prostate. J Clin Invest 99: 618-627, 1997.

  • 7. Nevalainen MT, Valve EM, Ahonen TA Yagi A, Paranko J, Härkönen PL. Androgen-dependent expression of prolactin in rat prostate epithelium in vivo and in organ culture. FASEB J. 11:1297-1308, 1997.

  • 8. Kallajoki M, Alanen KA, Nevalainen MT, Nurmi M, Nevalainen TJ. Expression of group II Phospholipase A2 in male reproductive organs and male genital tumors. Prostate 35: 263-272, 1998.

  • 9. Ahonen T, Harkonen PL, Laine J, Rui H, Martikainen PM, Nevalainen MT. Prolactin is a survival factor in androgen-deprived rat dorsal and lateral prostate in organ culture. Endocrinology 140: 5412-5421, 1999.

  • 10. Nevalainen MT, Ahonen TJ, Yamashita H, Chandrashekar S, Bartke A, Grimley PM, Robinson GW, Hennighausen L, Rui H. Epithelial defect in prostates of Stat5a -deficient mice. Lab Invest 80: 993-1006, 2000.

  • 11. Uotila P, Valve E, Martikainen P, Nevalainen MT, Nurmi M, Harkonen P. Increased expression of cyclo-oxygenase-2 and nitric oxide synthase-2 in human prostate cancer. Urological Research 29:25-28, 2001.

  • 12. Valve E, Nevalainen MT, Nurmi M, Martikainen P, Harkonen P. Increased expression of FGF-8 isoforms and FGF receptors in human premalignant prostatic intraepithelial neoplasia and prostate cancer. Lab Invest 81:815-826, 2001.

  • 13. Yamashita H, Nevalainen MT, Xu J, LeBaron M, Wagner KU, Erwin RA, Harmon G, Hennighausen L, Kirken RA, Rui H. Role of serine phosphorylation of Stat5a in prolactin-stimulated beta-casein gene expression. Mol Cell Endocrinol, 183:151-163, 2001.

  • 14. Ahonen T, Harkonen PL, Rui H, Nevalainen MT. Prolactin signal transduction in the epithelial compartment of rat prostate maintained as long-term organ cultures in vitro. Endocrinology, 143:228-238, 2002.

  • 15. Xie J, LeBaron MJ, Nevalainen MT, Rui H. Role of tyrosine kinase Jak2 in prolactin-induced differentiation and growth of mammary epithelial cells. J. Biol. Chem., 277:14020-14030, 2002.

  • 16. Nevalainen MT, Xie J, Bubendorf L, Wagner KU, Rui H. Basal activation of transcription factor Stat5 in nonpregnant mouse and human breast epithelium. Mol. Endocrinol., 16:1108-1124, 2002.

  • 17. Rui H, Nevalainen MT. Prolactin. In: Cytokine Handbook, 4th Edition, Angus Thomson and Michael T Lotze (eds), Academic Press, London, UK. Elsevier Science Ltd, London, pp 113-146, 2003.

  • 18. Tommi J. Ahonen, Jianwu Xie, Matthew J. LeBaron, Jianqiong Zhu, Martti Nurmi, Kalle Alanen, Hallgeir Rui, Marja T. Nevalainen. Inhibition of transcription factor Stat5 induces cell death of human prostate cancer cells. J. Biol. Chem. 278:27287-27292, 2003.

  • 19. Marja T. Nevalainen, Jianwu Xie, Joachim Torhorst, Lukas Bubendorf, Philippe Haas, Juha Kononen, Guido Sauter, Hallgeir Rui. Transcription factor Stat5 activation and breast cancer prognosis. J. Clin. Oncology, 22, (11):2053-2060, 2004.

  • 20. Li H., Ahonen T.J., Alanen, K., Xie, J., LeBaron, M.J., Pretlow, T.G., Ealley, E.E., Zhang, J., Nurmi, M., Singh, B., Martikainen, P., Nevalainen, M.T. Activation of Signal Transducer and Activator of Transcription 5 (Stat5) in human prostate cancer is associated with high histological grade. Cancer Research, 64:4774-4782, 2004.

  • 21. Sultan AS, Xie J, LeBaron MJ, Ealley EL, Nevalainen MT, Rui H. Transcription factor Stat5 stimulates homotypic adhesion and inhibits invasive characteristics of human breast cancer cells. Oncogene, 24, 746-760, 2005.

  • 22. Li H, Zhang Y, Glass A, Zellweger T, Gehan E, Bubendorf L, Gelmann EP, Nevalainen MT. Activation of Signal Transducer and Activator of Transcription-5 (Stat5) in Prostate Cancer Predicts Early Recurrence. Clinical Cancer Res., 11:5863-5868, 2005.

  • 23. LeBaron MJ, Ahonen TJ, Nevalainen MT, Rui H. In vivo response-based identification of direct hormone target cell populations using high-density tissue arrays. Endocrinology, 148:989-1008, 2007.

  • 24. Dagvadorj A, Collins S, Jomain, J, Abdulghani J, Karras J, zellweger T, Li H, Alanen K, Mirtti T, Visakorpi T, Bubendorf L, Goffin V, Nevalainen MT. Autocrine Prolactin Promotes Prostate Cancer Cell Growth via Jak2-Stat5 Signaling Pathway. Endocrinology, 148:3089-3101, 2007.

  • 25. Popov VM, Wang C, Shirley LA, Rosenberg A, Li S, Nevalainen M, Fu M, Pestell RG. The Functional Significance of Nuclear Receptor Acetylation. Steroids, 72:221-230, 2007.

  • 26. Nevalainen M, Culig, Z: Transcription Factors Stat5 and Stat3: Key Survival Factors for Prostate Cancer Cells. Chapter in: Prostate Cancer: Signaling Networks, Genetics and New Treatment Strategies, Nevalainen MT, Pestell R (eds), Humana Press, 257-290, 2008.

  • 27. Book on: Prostate Cancer: Signaling Networks, Genetics and New Treatment Strategies, Nevalainen MT, Pestell R (eds), Humana Press, 2008.

  • 28. Powell M, Lisanti M, Nevalainen MT, Wang C, Pestell R: Epigenetic Modification and Acetylation of Androgen Receptor Regulate Prostate Cellular Growth. Chapter in: Prostate Cancer: Signaling Networks, Genetics and New Treatment Strategies, Nevalainen MT, Pestell R (eds), Humana Press, 147-161, 2008.

  • 29. Shyh-Han Tan, Ayush Dagvadorj, Feng Shen, Lei Gu, Zhiyoung Liao, Junaid Abdulghani, Ying Zhang, Edward P. Gelmann, Tobias Zellweger, Zoran Culig, Tapio Visakorpi, Lukas Bubendorf, Robert A. Kirken, James Karras, Marja T. Nevalainen. Transcription Factor Stat5 Synergizes with Androgen Receptor in Prostate Cancer Cells, Cancer Research 2008; 68: (1-13), January 1, 2008.

  • 30. Dagvadorj, A, Kirken, RA, Karras, J, Nevalainen, MT. Transcription Factor Stat5 Promotes Growth of Human Prostate Cancer Cells In Vivo. Clinical Cancer Research,14:1317-1324, 2008.

  • 31. Abdulghani J, Gu L, Dagvadorj A, Lutz J, Leiby B, Bonucelli G, Lisanti M, Zellweger T, Alanen K, Mirtti T, Visakorpi T, Bubendorf L, Nevalainen MT. Transcription Factor Stat3 Promotes Metastatic Behavior of Prostate Cancer. American Journal Pathology, 172:1717-1728, 2008. Featured in Uro.Today and ScienceNews.com.

  • 32. Tan S, Nevalainen MT. Transcription Factor Stat5 in Breast and Prostate Cancer. Endocrine Related Cancer, 15:367-390, 2008.

  • 33. Dagvadorj A, Tan ST, Cavalli L, Haddad B, Nevalainen MT. Androgen-Dependent and Highly Tumorigenic Human Prostate Cancer Cell Line Established from a Transplantable Primary CWR22 Tumor. Clinical Cancer Research, 14:6062-6072, 2008.Featured in UroToday.com, Nov. 12, 2008.

  • 34. Lynn Moretti Neilson, Agnes Witkiewicz, Abhijit Dasgupta, Terry Hyslop, Joachim Torhorst, Lukas Bubendorf, Philippe Haas, Marja T. Nevalainen, Guido Sauter, and Hallgeir Rui: Signal transducer and activator of transcription-3 and breast cancer prognosis. Submitted, Modern Pathology, 2008.

  • 35. Gu, L, Vogiatzi PV, Puhr M, Dagvadorj A, Lutz J, Ryder A, Addya S, Fortina P, Cooper C, Leiby C, Dasgupta A, Hyslop T, Bubendorf L, Mirtti T, Nevalainen MT. Stat5 Promotes Metastatic Behavior of Human Prostate Cancer Cells In Vitro and In Vivo. In Revision, Cancer Research, 2009.

  • 36. Gu L, Dagvadorj A, Lutz J, Leiby B, Bonucelli G, Lisanti M, Addya S, Fortina P, Dasgupta A, Hyslop T, Rhimm J, Bubendorf L, Nevalainen MT. Transcription Factor Stat3 Stimulates Metastatic Behavior of Human Prostate Cancer Cells In Vivo While Stat5 Has a Preferential Role in the Promotion of Prostate Cancer Cell Viability and Tumor Growth. In Revision, Am. J. Pathology, 2009.

  • 37. Gu L, Mirtti T, Alanen K, Edmonston T, Nevalainen MT. JAK2 V617F Mutation is Absent in Advanced Human Prostate Cancers. In Review, Cancer Epidemiology, Biomarkers & Prevention, 2009.

  • 38. Liao Z, Shen F, Dagavadorj A, Abdulghani J, Leiby B, Tan S, Nevalainen MT. Glucocorticoids Increase Transcriptional Activity of Stat5a/b and Growth of Prostate Cancer Cells Growth. In Review, Endocrine-Related Cancer, 2009.

  • 39. Liao Z, Nevalainen MT. Transcription Factor Stat5a/b as a Therapeutic Target Protein for Prostate Cancer. In Review, Int. J. Biochemistry and Cell Biology, 2009.

  • 40 . Vogiatzi P, Nevalainen MT:Jak2/Stat5 Signaling Axis and Novel Therapeutic Strategies in Prostate Cancer. Chapter in: Cutting Edge Therapies for Cancer in 21st Century. Claudio PP (Ed), Bentham Science Publishers Ltd. In Preparation.

Individual Expertise profile of Marja Nevalainen, M.D., Ph.D., Copyright © Marja Nevalainen, M.D., Ph.D..
Last Updated by Marja Nevalainen, M.D., Ph.D. : Friday, October 16, 2009 12:19:11 PM



Maintained by Jerome Buescher
Copyright © Thomas Jefferson University. All Rights Reserved.

 Printable Version

The Thomas Jefferson University web site, its contents and programs, is provided for informational and educational purposes only and is not intended as medical advice nor is it intended to create any physician-patient relationship. Please remember that this information should not substitute for a visit or a consultation with a health care provider. The views or opinions expressed in the resources provided do not necessarily reflect those of Thomas Jefferson University, Thomas Jefferson University Hospital, or the Jefferson Health System or staff.
Please read our Privacy Statement.
Thomas Jefferson University
Thomas Jefferson University