Nevalainen Laboratory

Location

Translational & Biomedical Resource Center
4th Floor

General Research Interests

Prostate Cancer Progression, Therapy and Predictive Biomarker Development, Jak-Stat5 Signaling, Androgen Receptor Signaling, DNA-Repair, Radiation Therapy, 3D Tumor Explant Cultures

View Marja Nevalainen Bio

Research Areas

Dr. Nevalainen is an internationally recognized leader in the field of Jak-Stat signaling in prostate cancer (PC). Dr. Nevalainen’s group provided the proof-of-concept that Stat5 is a therapeutic target protein for prostate cancer. Dr. Nevalainen’s group made the seminal finding of Stat5 as a critical factor for prostate cancer cell viability and growth in vitro, in vivo in xenograft tumor models and ex vivo in patient-derived clinical prostate cancers. Her group further established the concepts of 1) Stat5 as a critical promoter of castrate-resistant prostate cancer growth, 2) Stat5 as a predictive factor of early prostate cancer recurrence and disease-specific death after radical prostatectomy, 3) Stat5 as a promoter of prostate cancer stem cell properties, epithelial-to-mesenchymal transition and metastatic disease, 4) Stat5 as a regulator of homologous recombination DNA repair and radiation response of prostate cancer. In recent work, using medicinal chemistry Dr. Nevalainen and collaborators have identified a family of novel small molecule Stat5 inhibitors with high efficacy in both PC and Bcr-Abl-driven leukemias.

Dr. Nevalainen’s research accomplishments include development of an androgen-dependent human PC cell line which mimics the course of human disease when grown as xenograft tumors in nude mice. Specifically, the tumors response to androgen deprivation by regression but regrow eventually back as castrate-resistant tumors.

Dr. Nevalainen is further recognized in her field for early development of a long-term 3D tumor explant culture system for normal and malignant prostate tissue for efficacy testing of experimental biologics and small-molecules ex vivo in clinical PCs from patients and as an experimental model system for identification of growth factor and drug modulated signaling proteins in prostate tissue.

Current work focuses on Jak-Stat signaling in anti-androgen resistance of prostate cancer, Stat5 regulation of DNA repair and optimization of the lead compound Stat5 inhibitor.

Funding & Patents and Licensing Opportunities

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Current Funding

2019–2023 Co-Investigator (Nevalainen), Principal Investigator (Liang Wang), RO1; “Cell Free Nucleic Acid-Based Biomarkers in Advanced Prostate Cancer (PI: Liang Wang). NIH/NCI.

2019–2021 Principal Investigator (Nevalainen), (AHW 5520493); “Development of Predictive Test for Chemotherapy Selection for Individual Pancreatic Cancer Patients.” Advancing Healthier Wisconsin.

2019–2021 Principal Investigator (Nevalainen), (FP15437); “Stat5 and Anti-Androgen-Induced Metastatic Phenotype of Prostate Cancer”. Wisconsin Cancer Showhouse.

2019–2022 Principal Investigator (Nevalainen), Office of Technology Development at the MCW: “Jak2 Inhibitors and Prostate Cancer Growth."

2020–2023 Principal Investigator (Nevalainen), American Cancer Society Institutional Research Grant (134108-IRG-19-138-34-IRG), MCW Cancer Center. American Cancer Society.

2022–2027 Contact Principal Investigator (Nevalainen), (M-PI, Scott Dehm, Univ. of Minnesota), 1RO1CA262570-01A1; “Pharmacological Jak2 Inhibition to Overcome Androgen Receptor Aberrations in Prostate Cancer." NCI/NIH.

Patents and Licensing Opportunities

2020 Conversion of US Provisional Patent Application; Office of Technology Development, Medical College of Wisconsin. Inventors: Marja T Nevalainen: Methods of Treating Advanced Prostate Cancer”, 650053.00611, MCW 2068; Pending (Filed July 29, 2019)

2019 US Provisional Patent Application, 2019. Office of Technology Development, Medical College of Wisconsin. Inventors: Marja T Nevalainen: Methods of Treating Advanced Prostate Cancer”, 650053.00611, MCW 2068; Pending (Filed July 29, 2019)

2007 United States Patent 7,306,921. Diagnostic and Monitoring Methods for Cancer. Inventors: Nevalainen, MT, Rui, H. Filed Jan 2001. Issued, 2007.

2010 United States Patent 7,642,050. Method for predicting responsiveness of breast cancer to antiestrogen therapy. Inventors: Nevalainen, MT, Rui, H. Filed Jan 2001. Issued, 2010.

2012 United States Patent 1212/548,383. Methods and Compositions for the Inhibition of Stat5 in Prostate Cancer Cells (RNA interference). Inventor; Marja T. Nevalainen. Filed April 2003. Issued, 2012.

2013 United States Patent 13/477,923. Methods and Compositions for the Inhibition of Stat5 in Prostate Cancer Cells (Antibodies and Small Molecules). Inventor; Marja T. Nevalainen. Filed May 2012.

High PD-L2 Predicts Early Recurrence of ER-Positive Breast Cancer.

(Chervoneva I, Peck AR, Sun Y, Yi M, Udhane SS, Langenheim JF, Girondo MA, Jorns JM, Chaudhary LN, Kamaraju S, Bergom C, Flister MJ, Hooke JA, Kovatich AJ, Shriver CD, Hu H, Palazzo JP, Bibbo M, Hyslop T, Nevalainen MT, Pestell RG, Fuchs SY, Mitchell EP, Rui H.) JCO Precis Oncol. 2023 Jan;7:e2100498 PMID: 36652667 PMCID: PMC9928763 01/19/2023
Multi-Site Concordance of Diffusion-Weighted Imaging Quantification for Assessing Prostate Cancer Aggressiveness.

(McGarry SD, Brehler M, Bukowy JD, Lowman AK, Bobholz SA, Duenweg SR, Banerjee A, Hurrell SL, Malyarenko D, Chenevert TL, Cao Y, Li Y, You D, Fedorov A, Bell LC, Quarles CC, Prah MA, Schmainda KM, Taouli B, LoCastro E, Mazaheri Y, Shukla-Dave A, Yankeelov TE, Hormuth DA 2nd, Madhuranthakam AJ, Hulsey K, Li K, Huang W, Huang W, Muzi M, Jacobs MA, Solaiyappan M, Hectors S, Antic T, Paner GP, Palangmonthip W, Jacobsohn K, Hohenwalter M, Duvnjak P, Griffin M, See W, Nevalainen MT, Iczkowski KA, LaViolette PS.) J Magn Reson Imaging. 2022 Jun;55(6):1745-1758 PMID: 34767682 PMCID: PMC9095769 SCOPUS ID: 2-s2.0-85118887092 11/13/2021
Spatial Metrics of Interaction between CD163-Positive Macrophages and Cancer Cells and Progression-Free Survival in Chemo-Treated Breast Cancer.

(Maisel BA, Yi M, Peck AR, Sun Y, Hooke JA, Kovatich AJ, Shriver CD, Hu H, Nevalainen MT, Tanaka T, Simone N, Wang LL, Rui H, Chervoneva I.) Cancers (Basel). 2022 Jan 08;14(2) PMID: 35053472 PMCID: PMC8773496 01/22/2022
Second-Generation Jak2 Inhibitors for Advanced Prostate Cancer: Are We Ready for Clinical Development?

(Beinhoff P, Sabharwal L, Udhane V, Maranto C, LaViolette PS, Jacobsohn KM, Tsai S, Iczkowski KA, Wang L, Hall WA, Dehm SM, Kilari D, Nevalainen MT.) Cancers (Basel). 2021 Oct 17;13(20) PMID: 34680353 PMCID: PMC8533841 10/24/2021
NSG-Pro mouse model for uncovering resistance mechanisms and unique vulnerabilities in human luminal breast cancers.

(Sun Y, Yang N, Utama FE, Udhane SS, Zhang J, Peck AR, Yanac A, Duffey K, Langenheim JF, Udhane V, Xia G, Peterson JF, Jorns JM, Nevalainen MT, Rouet R, Schofield P, Christ D, Ormandy CJ, Rosenberg AL, Chervoneva I, Tsaih SW, Flister MJ, Fuchs SY, Wagner KU, Rui H.) Sci Adv. 2021 Sep 17;7(38):eabc8145 PMID: 34524841 PMCID: PMC8443188 SCOPUS ID: 2-s2.0-85115168052 09/16/2021
Updates and new directions in the use of radiation therapy for the treatment of pancreatic adenocarcinoma: dose, sensitization, and novel technology.

(Hall WA, Kamgar M, Erickson BA, Ponce SB, Tsai S, Nevalainen MT, Christians KK, George B, Dua KS, Khan AH, Evans DB, Azmi AS.) Cancer Metastasis Rev. 2021 Sep;40(3):879-889 PMID: 34611794 PMCID: PMC8767496 SCOPUS ID: 2-s2.0-85116412346 10/07/2021
Prospects for Clinical Development of Stat5 Inhibitor IST5-002: High Transcriptomic Specificity in Prostate Cancer and Low Toxicity In Vivo.

(Maranto C, Udhane V, Jia J, Verma R, Müller-Newen G, LaViolette PS, Pereckas M, Sabharwal L, Terhune S, Pattabiraman N, Njar VCO, Imig JD, Wang L, Nevalainen MT.) Cancers (Basel). 2020 Nov 18;12(11) PMID: 33217941 PMCID: PMC7724566 SCOPUS ID: 2-s2.0-85096199725 11/22/2020
Cytokines, JAK-STAT Signaling and Radiation-Induced DNA Repair in Solid Tumors: Novel Opportunities for Radiation Therapy.

(Hall WA, Sabharwal L, Udhane V, Maranto C, Nevalainen MT.) Int J Biochem Cell Biol. 2020 Oct;127:105827 PMID: 32822847 PMCID: PMC8638530 SCOPUS ID: 2-s2.0-85090734995 08/22/2020
Accurate segmentation of prostate cancer histomorphometric features using a weakly supervised convolutional neural network.

(Bukowy JD, Foss H, McGarry SD, Lowman AK, Hurrell SL, Iczkowski KA, Banerjee A, Bobholz SA, Barrington A, Dayton A, Unteriner J, Jacobsohn K, See WA, Nevalainen MT, Nencka AS, Ethridge T, Jarrard DF, LaViolette PS.) J Med Imaging (Bellingham). 2020 Sep;7(5):057501 PMID: 33062803 PMCID: PMC7550797 10/17/2020
Enzalutamide-Induced Feed-Forward Signaling Loop Promotes Therapy-Resistant Prostate Cancer Growth Providing an Exploitable Molecular Target for Jak2 Inhibitors.

(Udhane V, Maranto C, Hoang DT, Gu L, Erickson A, Devi S, Talati PG, Banerjee A, Iczkowski KA, Jacobsohn K, See WA, Mirtti T, Kilari D, Nevalainen MT.) Mol Cancer Ther. 2020 Jan;19(1):231-246 PMID: 31548294 PMCID: PMC6946850 SCOPUS ID: 2-s2.0-85077669370 09/25/2019
Positive STAT5 Protein and Locus Amplification Status Predicts Recurrence after Radical Prostatectomy to Assist Clinical Precision Management of Prostate Cancer.

(Haddad BR, Erickson A, Udhane V, LaViolette PS, Rone JD, Kallajoki MA, See WA, Rannikko A, Mirtti T, Nevalainen MT.) Cancer Epidemiol Biomarkers Prev. 2019 Oct;28(10):1642-1651 PMID: 31292140 PMCID: PMC6774884 SCOPUS ID: 2-s2.0-85072849403 07/12/2019
Gleason Probability Maps: A Radiomics Tool for Mapping Prostate Cancer Likelihood in MRI Space.

(McGarry SD, Bukowy JD, Iczkowski KA, Unteriner JG, Duvnjak P, Lowman AK, Jacobsohn K, Hohenwalter M, Griffin MO, Barrington AW, Foss HE, Keuter T, Hurrell SL, See WA, Nevalainen MT, Banerjee A, LaViolette PS.) Tomography. 2019 Mar;5(1):127-134 PMID: 30854450 PMCID: PMC6403022 SCOPUS ID: 2-s2.0-85071529534 03/12/2019

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