balkDr. Balk's main objective has been to conduct disease focused integrated basic and translational research and to equip MD and/or PhD trainees to do the same. The initial focus of his lab was immunology, but in 1993 he initiated a major research effort in prostate cancer (PCa).

His lab developed methods to analyze advanced metastatic PCa through the use of bone marrow biopsies and showed that one mechanism for disease progression after androgen deprivation therapy was through mutations in the androgen receptor (AR). These mutations occur specifically in patients treated with an AR antagonist, flutamide, and are the result of strong selective pressure exerted by this drug. In subsequent studies his lab has further established a critical role for AR in PCa that relapses after androgen deprivation therapy, and identified mechanisms that mediate AR reactivation (including enhanced androgen synthesis by tumor cells). These results have led directly to successful clinical trials with translational as well as clinical endpoints. An additional current focus is mechanisms of progression from low grade to high grade prostate cancer, which will have an impact on management of low grade disease. In conjunction with these research efforts, he has directed the establishment of a prostate cancer tissue bank and correlative clinical database.

His teaching efforts have focused primarily on exposing clinical fellows to basic research and mentoring them in the conduct of translational and clinical research, and in training basic research PhDs. His major clinical contributions are currently in the expansion of our clinical database and tissue bank for PCa and in the design and execution of clinical trials.

Email Dr. Balk

Positions:

Intern in Medicine, New England Deaconess Hospital, Boston, MA: 1983-1984
Resident in Medicine, New England Deaconess Hospital, Boston, MA: 1984-1985
Clinical Fellow in Medicine (Hematology/Oncology), Beth Israel Hospital, and Harvard Medical School, Boston, MA: 1985-1988
Research Fellow, Beth Israel Hospital, Dana Farber Cancer Institute, and Harvard Medical School Boston, MA: 1986-1988
Instructor in Medicine, Harvard Medical School, Boston, MA: 1988-1992
Staff Physician, Beth Israel Deaconess Medical Center, Boston, MA: 1988-present
Assistant Professor of Medicine, Harvard Medical School, Boston, MA: 1992-1998
American Society for Clinical Investigation, member: 1996-present
Associate Professor of Medicine, Harvard Medical School, Boston, MA: 1998-2010
Director, DNA Sequencing, quantitative RT-PCR, Laser Capture Microdissection Core Facilities, BIDMC: 2000-present
Assistant Director, BIDMC Training Grant in Cancer Biology: 2002-2006
Associate Editor, Journal of Immunology: 2002-2006
Director, BIDMC Training Grant in Cancer Biology: 2007-present
Association of American Physicians: 2010-present
Professor of Medicine, Harvard Medical School, Boston, MA: 2010-present
Senior Editor, Cancer Research: 2013-present

Education:

B.A.: University of Pennsylvania: 1976
M.D.: Harvard-MIT Health Sciences and Technology Program: 1983
Ph.D.: Harvard University (Ph.D., Cell & Develop. Biology): 1983

Licensure and Certification:

Massachusetts Medical License: 1984
American Board of Internal Medicine: 1986

Major Committee Assignments:

Hospital/Medical School:
Hematology-Oncology Fellowship Selection Committee, BIDMC: 1998-present
Steering Committee, Harvard Translational Immunology Center, Harvard
University: 2005
Harvard-MIT Health Sciences and Technology (HST) Admission Committee: 2007-present
Ph.D. Program in Biological and Biomedical Sciences (BBS): 2007-present
Harvard Program in Human Biology and Translational Medicine (HBTM): 2007-present

National:
Biochemical Endocrinology Study Section ad hoc reviewer NIH: 1997
Prostate Cancer Study Section ad hoc reviewer DOD: 1999-2005
Biochemical Endocrinology Study Section ad hoc reviewer NIH: 1999
SEP: Sex Based Differences in Immunity ad hoc reviewer NIH: 2001
Immunological Sciences Study Section ad hoc reviewer NIH: 2001
Experimental Immunology Study Section ad hoc reviewer NIH: 2002
Biochemical Endocrinology Study Section ad hoc reviewer NIH: 2002
SEP: Radiation Study Section ad hoc reviewer NIH: 2002
SEP: Environmental Health Sciences ad hoc reviewer NIH: 2002
Immunological Sciences Study Section ad hoc reviewer NIH: 2003
SEP: Urology Research Centers ad hoc reviewer NIH: 2003
SEP: Urology Development of Cell… ad hoc reviewer NIH: 2003
Subcommittee C, Prostate Cancer Section ad hoc reviewer NIH: 2004
Transplantation, Tolerance, and Tumor ad hoc reviewer NIH
Immunology Study Section: 2004
Urologic and Kidney Development and ad hoc reviewer NIH
Genitourinary Diseases Study Section: 2004
Subcommittee E, Cancer Epidemiology, ad hoc reviewer NIH
Prevention, and Control: 2005
Prostate Cancer Study Section ad hoc reviewer DOD: 2005
Prostate Cancer Program ad hoc reviewer NCI-Canada: 2005
Transplantation, Tolerance, and Tumor ad hoc reviewer NIH
Immunology Study Section: 2006
Co-chair, Androgen Working Group, NCI-
Prostate SPORE program: 2007
Urologic and Kidney Development and ad hoc reviewer NIH
Genitourinary Diseases Study Section: 2007
Louisiana Board of Regents Research Grants ad hoc reviewer: 2007
NCI-F Manpower & Training Grants Study ad hoc reviewer NIH
Section: 2007
Tumor Microenvironment Study Section ad hoc reviewer NIH: 2008
Urologic and Kidney Development and ad hoc reviewer NIH
Genitourinary Diseases Study Section: 2008
NCI-F Manpower & Training Grants Study Section member NIH: 2008-2012
Department of Defense Prostate Cancer Research Program DOD Integration Panel: 2008-2009
Cancer Molecular Pathology Study Section ad hoc reviewer NIH: 2012

Awards and Honors:

NCI, Physician Scientist Award: 1987
American Cancer Society Junior Faculty Research Award: 1992
Prostate Cancer Foundation Challenge Award: 2008

Funding Information:

NIH-Physician Scientist Award, PI, Regulation of CD1 Gene Expression: 1987-1990
Shiseido Corporation/Massachusetts General Hospital, Co-PI, Double Negative T Cells in Skin: 1988-1990
American Cancer Society-Junior Faculty Research Award, PI, Regulation of CD1 Gene Expression: 1990-1993
NIH R01 CA54062, Co-PI, Clonal Analysis of Cutaneous T Cell Lymphomas: 1992-1996
NIH RO1 DK44319, Co-PI, Molecular Characterization of Mucosal Lymphocytes: 1992-1999
NIH RO1 AI33911, PI, Function of Human Intestinal Intraepithelial Lymphocytes: 1993-2003
NIH RO1 CA65647, PI, AR Mutations in Androgen Independent Prostate Cancer: 1995-1999
American Cancer Society Research Award, Co-PI, Casodex Therapy and Androgen Receptors: 1995-1997
Commonwealth of Massachusetts Prostate Cancer Research Award, PI, Transgenic Androgen Receptor Overexpression as a Murine Prostate Cancer Model: 1997-1998
Crohn's and Colitis Foundation of America, Co-PI, Characterization of CD1d and its Interacting Proteins in Intestinal: 1997-1999
Epithelial Cells and Hepatocytes NIH R21 AI42955, PI, Immune Regulation by CD1d Reactive NKR-P1 T cells: 1998-1999
NIH R01 AI42955, PI, Immune Regulation by CD1d Reactive NKR-P1 T cells: 1999-2004
NIH R21 CA89611, PI, Invariant NK T Cells for Phase 1 Cancer Trials: 2001-2003
DOD Breast Cancer Research Program (BC001045), PI, Tamoxifen Dependent Interaction Between the Estrogen Receptor and a Novel p21 Activated Kinase: 2001-2004
NIH P01CA89021, Co-PI, project 1 The Role of PTEN and PI3K Pathway in Prostate Cancer; Project 1: Role of PI3K Regulatory Subunits in Prostate Cancer (L. Cantley PI of P01): 2001-2006
NIH R01 DK61047, PI, AR Transgene Model of Prostate Intraepithelial Neoplasia: 2002-2008
NIH P50 CA090381, PI-project 4, SPORE in Prostate Cancer Project 4: The Androgen Receptor in Hormone Refractory Disease (P. Kantoff PI of SPORE): 2002-2007
DOD Prostate Cancer Research Program, PI, Idea Development Award (PC040246) AR-NCoR Interaction as a Therapeutic Target for Prostate Cancer Prevention and Treatment: 2004-2007
GlaxoSmithKline, PI, Clinical Trial of Ketoconozole, Hydrocortisone, and Dutasteride in Androgen Independent Prostate Cancer: 2006-2009
NIH R21 NS057051, PI, High Throughput Screen for Androgen Receptor Antagonists that Recruit NCoR: 2006-2008
NIH T32 CA081156, PI, Training Grant in Cancer Biology: 2007-2012
DOD Prostate Cancer Research Program, PI, Idea Development Award (PC060807) Androgen Metabolism in Progression to Androgen Independent Prostate Cancer: 2007-2010
NIH P50 CA090381, PI-project 4, SPORE in Prostate Cancer Project 4: The Androgen Receptor in Hormone Refractory Disease (P. Kantoff PI of SPORE): 2007-2012
NIH R01CA11803, PI, Targeting AR-NCoR Interaction in Prostate Cancer: 2007-2012
DOD Prostate Cancer Research Program, PI, Idea Development Award (PC073779) Identification and Targeting of Upstream Tyrosine Kinases Mediating PI3 Kinase Activation in PTEN Deficient Prostate Cancer: 2008-2011
Prostate Cancer Foundation, Androgen Receptor Consortium, PI, Challenge Award: 2008-2011
DOD Prostate Cancer Research Program, PI, Laboratory-Clinical Translational Award (PC081107) Invariant NKT cell Ligands for Prostate Cancer Vaccines: 2009-2012
DOD Prostate Cancer Research Program, PI, Idea Development Award (PC081119) Preclinical Assessment of Bmx/Etk Inhibitors for Prostate Cancer: 2009-2012
Prostate Cancer Foundation, Honorable A. David Mazzone, PI, Special Challenge Award Research Identifying and Exploiting Mechanisms of Response and Resistance to Androgen Receptor Pathway Directed Therapeutics: 2011-2013
DOD Prostate Cancer Research Program, PI, Idea Development Award (PC100933) Validation of ERG as a Therapeutic Target in Advanced Prostate Cancer: 2011-2014
DOD Prostate Cancer Research Program, PI, Idea Development Award (PC100950) Molecular Mechanisms Contributing to Relapse after CYP17 Inhibition: 2011-2014
Dana Farber/Harvard Cancer Center Impact Award, PI, Mechanisms Mediating Progression of Gleason 3 Prostate Cancers: 2012-2014
Stand Up 2 Cancer Prostate Dream Team, PI, Chinnaiyan/Sawyers Precision Therapy for Advanced Prostate Cancer: 2012-2015
V Foundation for Cancer Research, PI, Molecular Characterization of Gleason 3 Tumors that Progress to Gleason 4: 2012-2015
DOD Prostate Cancer Research Program, PI, Idea Development Award (PC120387) Regulation of AR Degradation and Function by Ubiquitylation: 2013-2016
NIH P01 CA163227-01A1, PI, Androgen Receptor Action in Castration Resistant Prostate Cancer: 2013-2018

Recent Publications (click underlined to go to publication):

Click here to go to full list in Pubmed.

  1. F. Ma, H. Ye, H. H. He, S. J. Gerrin, S. Chen, B. Tanenbaum, C. Cai, A. G. Sowalsky, L. He, H. Wang, S. P. Balk, and X. Yuan. SOX9 drives WNT pathway activation in prostate cancer . J Clin Invest. 2016;126(5):1745-1758. doi:10.1172/JCI78815. Epub 2016 Apr 4.

  2. Gao S, Ye H, Gerrin S, Wang H, Sharma A, Chen S, Patnaik A, Sowalsky AG, Voznesensky O, Han W, Yu Z, Mostaghel EA, Nelson PS, Taplin ME, Balk SP, Cai C. ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer. Clin Cancer Res. 2016 Mar 2. [Epub ahead of print]PMID: 26936914

  3. Sowalsky AG, Xia Z, Wang L, Zhao H, Chen S, Bubley GJ, Balk SP, Li W. (2015). Whole Transcriptome Sequencing Reveals Extensive Unspliced mRNA in Metastatic Castration-Resistant Prostate Cancer. Mol Cancer Res. 13:98-106.

  4. Cai C, He HH, Gao S, Chen S, Yu Z, Gao Y, Chen S, Chen MW, Zhang J, Ahmed M, Wang Y, Metzger E, Schüle R, Liu XS, Brown M, Balk SP. (2014). Lysine-specific demethylase 1 has dual functions as a major regulator of androgen receptor transcriptional activity. Cell Rep. 9:1618-27.

  5. Chen EJ, Sowalsky AG, Gao S, Cai C, Voznesensky O, Schaefer R, Loda M, True LD, Ye H, Troncoso P, Lis RL, Kantoff PW, Montgomery RB, Nelson PS, Bubley GJ, Balk SP, and Taplin ME. (2015). Abiraterone Treatment in Castration-Resistant Prostate Cancer Selects for Progesterone Responsive Mutant Androgen Receptors. Clin Cancer Res 21, 1273-1280.

  6. Yu, Z., Cai, C., Gao, S., Simon, N. I., Shen, H. C., and Balk, S. P. (2014). Galeterone prevents androgen receptor binding to chromatin and enhances degradation of mutant androgen receptor. Clin Cancer Res 20, 4075-4085.

  7. Chin, Y.M., Yuan, X., Balk, S.P., and Toker, A. (2014). Pten-deficient tumors depend on Akt2 for maintenance and survival. Cancer Discov., 4, 942-955.

  8. Yu, Z., Chen, S., Sowalsky, A.G., Voznesensky, O., Mostaghel, E.A., Nelson, P.S., Cai, C., and Balk, S.P. (2014). Rapid Induction of Androgen Receptor Splice Variants by Androgen Deprivation in Prostate Cancer. Clin Cancer Res., 20: 1590-1600.

  9. Chen, S., Jiang, X., Gewinner, C.A., Asara, J.M., Simon, N.I., Cai, C., Cantley, L.C., and Balk, S.P. (2013). Tyrosine Kinase BMX Phosphorylates Phosphotyrosine-Primed Motif Mediating the Activation of Multiple Receptor Tyrosine Kinases. Science Signaling, 6, ra40.

  10. Cai, C., Wang, H., He, H.H., Chen, S., He, L., Ma, F., Mucci, L., Wang, Q., Fiore, C., Sowalsky, A.G., Loda, M., Liu, X.S., Brown, M., Balk, S.P., and Yuan, X. (2013). ERG Induces Androgen Receptor-Mediated Regulation of SOX9 in Prostate Cancer. J Clin Invest 123, 1109-1122.

Book Chapters, Letters, and Reviews:

24. Yuan, X., Cai, C., Chen, S., Chen, S., Yu, Z. and Balk, S.P. (2013). Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis. Oncogene, Jun 10.
23. Cai, C., and Balk, S.P. (2011). Intratumoral androgen biosynthesis in prostate cancer pathogenesis and response to therapy. Endocr Relat Cancer 18, R175-182.
22. Exley, M.A., Lynch, L., Varghese, B., Nowak, M., Alatrakchi, N., and Balk, S.P. (2011). Developing understanding of the roles of CD1d-restricted T cell subsets in cancer: Reversing tumor-induced defects. Clin Immunol 140, 184-195.
21. Shen,H.C. and Balk,S.P. (2009). Development of androgen receptor antagonists with promising activity in castration-resistant prostate cancer. Cancer Cell 15, 461-463.
20. Yuan X, Balk SP. Mechanisms mediating androgen receptor reactivation after castration. Urol Oncol 2009;27:36-41.
19. Balk,S.P. and Knudsen,K.E. (2008). AR, the cell cycle, and prostate cancer. Nucl. Recept. Signal. 6, e001
18. van der Vliet,H.J., Koon,H.B., Atkins,M.B., Balk,S.P., and Exley,M.A. (2007). Exploiting regulatory T-cell populations for the immunotherapy of cancer. J. Immunother. 30, 591-595.
17. Probert,C.S., Saubermann,L.J., Balk,S., and Blumberg,R.S. (2007). Repertoire of the alpha beta T-cell receptor in the intestine. Immunol. Rev. 215, 215-225.
16. van der Vliet,H.J., Balk,S.P., and Exley,M.A. (2006). Natural killer T cell-based cancer immunotherapy. Clin. Cancer Res. 12, 5921-5923.
15, Reddy,G.K. and Balk,S.P. (2006). Clinical utility of microarray-derived genetic signatures in predicting outcomes in prostate cancer. Clin. Genitourin. Cancer 5, 187-189.
14. Ko,Y.J. and Balk,S.P. (2004). Targeting steroid hormone receptor pathways in the treatment of hormone dependent cancers. Curr. Pharm. Biotechnol. 5, 459-470.
13. Taplin,M.E. and Balk,S.P. (2004). Androgen receptor: a key molecule in the progression of prostate cancer to hormone independence. J. Cell Biochem. 91, 483-490.
12. Cheng,S. and Balk,S.P. (2003). Steroid hormone receptor signaling in cancer. Cancer Treat. Res. 115, 293-318.
11. Balk,S.P., Ko,Y.J., and Bubley,G.J. (2003). Biology of prostate-specific antigen. J. Clin. Oncol. 21, 383-391.
10. Carroll,P.R., Kantoff,P.W., Balk,S.P., Brown,M.A., D'amico,A.V., George,D.J., Grossfeld,G.D., Johnson,C.S., Kelly,W.K., Klotz,L., Lee,W.R., Lubeck,D.P., Mcleod,D.G., Oh,W.K., Pollack,A., Sartor,O., Smith,M.R., and Hart,C. (2002). Overview consensus statement. Newer approaches to androgen deprivation therapy in prostate cancer. Urology 60, 1-6.
9. Balk,S.P. (2002). Androgen receptor as a target in androgen-independent prostate cancer. Urology 60, 132-138.
8. Blumberg,R.S., Colgan,S.P., and Balk,S.P. (1997). CD1d: outside-in antigen presentation in the intestinal epithelium? Clin. Exp. Immunol. 109, 223-225.
7. Bubley,G.J. and Balk,S.P. (1996). Treatment of Androgen-Independent Prostate Cancer. Oncologist. 1, 30-35.
6. Bubley,G.J. and Balk,S.P. (1996). Treatment of metastatic prostate cancer. Lessons from the androgen receptor. Hematol. Oncol. Clin. North Am. 10, 713-725.
5. Blumberg,R.S., Gerdes,D., Chott,A., Porcelli,S.A., and Balk,S.P. (1995). Structure and function of the CD1 family of MHC-like cell surface proteins. Immunol. Rev. 147, 5-29.
4. Balk,S. (1995). MHC evolution. Nature 374, 505-506.
3. Blumberg,R.S. and Balk,S.P. (1994). Intraepithelial lymphocytes and their recognition of non-classical MHC molecules. Int. Rev. Immunol. 11, 15-30.
2. Balk,S. and Terhorst,C. (1989). Relationship between the T-cell receptor-T3 complex and Thy-1. Immunol. Ser. 45, 411-416.
1. Bleicher,P.A. and Balk,S.P. (1988). T-cell receptor gene rearrangements. Progress and promise. Arch. Dermatol. 124, 359-363.

Patents:

PCT/US2011/064852 filed Dec. 14, 2011, Androgen Receptor Antagonists for Prostate Cancer Therapy

Link to Dr. Balk's Harvard Catalyst Page