CURRICULUM VITAE

BART O. WILLIAMS Van Andel Research Institute 333 Bostwick NE Grand Rapids, MI 49503

Telephone: (616)-234-5308 Fax: (616)-234-5309 Email: [email protected] http://www.vai.org/vari/labs/williams.asp

Place of Birth: Madison, Wisconsin

Education

Carroll College, Waukesha, WI B.S. 1991 Biology and Chemistry

Massachusetts Institute of Technology, Cambridge, MA Ph.D. 1996 Biology

Awards and Honors

1987-1991 Presidential Scholarship Award, Carroll College 1988 American Association of University Professors Award for Sophomores 1989 Undergraduate Research Grant Award from the National Science Foundation (through the Center for Great Lakes Studies, Milwaukee, WI) 1990 Delta Sigma Nu Scholastic Honor Society 1990 and 1991 USA Today's All-USA Academic Third Team 1991 Outstanding Senior Biology Student, Carroll College 1996 Young Investigator Travel Grant Award, AACR Meeting, Lausanne, Switzerland (January 17-20, 1996) 1996-1999 Postdoctoral Fellowship Award from the Damon Runyon-Walter Winchell Research Fund 2004 Most Outstanding Abstract Award, American Society for Bone and Mineral Research Annual Meeting, Seattle, Washington

Professional Experience

1989-1990 Undergraduate Research Student, Carroll College, Department of Biology, Waukesha, WI (Leslie D. Zettergren, Advisor) 1990-1991 Undergraduate Research Student, Medical College of Wisconsin, Department of Biochemistry, Milwaukee, WI (Arthur L. Haas, Advisor) 1991-1996 Graduate Student, Department of Biology and Center for Cancer Research, MIT, Cambridge, MA (Tyler Jacks, Advisor) 1996-1999 Damon Runyon-Walter Winchell postdoctoral fellow, National Cancer Institute, NIH, Bethesda, MD (Harold E. Varmus, Advisor) 2003- Clinical Assistant Adjunct Professor, College of Veterinary Medicine, Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 1999-2006 Investigator, Van Andel Research Institute, Grand Rapids, MI 2006- Associate Professor (Senior Investigator), Van Andel Research Institute, Grand Rapids, MI 2010- Director, Center for Skeletal Disease Research, Van Andel Research Institute, Grand Rapids, MI

Teaching Experience

1989 Teaching Assistant - Introductory Biology Laboratory, Carroll College (Dr. Ted Michaud, Instructor) 1989-1991 Tutor for Introductory Biology Lectures, Carroll College (Dr. Ted Michaud, Dr. John Clausz, and Dr. John Mellen, Instructors) 1990 Teaching Assistant - Microbiology Laboratory, Carroll College (Dr. John Clausz, Instructor) 1990 Teaching Assistant - Comparative Anatomy Laboratory, Carroll College (Dr. Ted Michaud, Instructor) 1992 Teaching Assistant - Experimental Molecular Biology Laboratory, Massachusetts Institute of Technology (Dr. Phillips Robbins, Instructor) 1994 Teaching Assistant - Undergraduate Cell Biology, Massachusetts Institute of Technology (Dr. Richard Young and Dr. Tyler Jacks, Instructors) 2004-2009 Curriculum Development and Assessment Committee for Van Andel Institute Graduate School in Biomedical Sciences 2005-2011 Lecturer, Short Course in Integrative and Organ System Pharmacology and Toxicology, Michigan State University. 2006 Coordinator and Lecturer, Michigan State University/VARI Mouse Models for Human Disease Course (Genetics/CMB 800 Fall 2006) 2007-2011 Coordinator and Lead Instructor, Historical Perspectives in Molecular, Cellular, and Developmental Biology, Van Andel Institute Graduate School. 2008 Coordinator and Lead Instructor, Strategic Approaches in Biomedical Research, Module, Van Andel Institute Graduate School 2009-2011 Coordinator and Lead Instructor, Strategic Approaches in Biomedical Research, Breast and Module, Van Andel Institute Graduate School

Professional Memberships

American Association of Cancer Research Advances in Mineral Metabolism American Society for Biochemistry and Molecular Biology American Society for Bone and Mineral Research International Bone and Mineral Society

Advisory Boards

Vice President, Board of Directors, Antel BioSystems, Lansing, MI, 2003-present Member, External Advisory Board, Prostate Cancer Program Project Grant (Evan Keller, PI), 2007-present Post-doctoral Fellows

Sheri Holmen, 2000-2003 PhD (2000) Mayo Clinic, Rochester, MN Current Position: Associate Professor, Huntsman Cancer Institute, Salt Lake City, UT

Troy Giambernardi, 2000-2005 PhD (2000) University of Texas-San Antonio Current Position: Assistant Professor, Biological Sciences Department, Grand Rapids Community College, Grand Rapids, MI

Charlotta Lindvall, 2003-2009 MD/PhD (2002) Karolinska Institute (Stockholm, Sweden) Current Position, Adjunct Professor, Van Andel Research Institute and Clinical Resident in Internal Medicine, Grand Rapids Medical Education Partners

Zhen-Dong (Alex) Zhong, 2009-present PhD (2009) Sun yat-sen University of Medical Science, Guangzhou, China

Graduate Students

Ken Valkenburg, 2010- present Thesis: Role of Wnt signaling in prostate cancer and prostate cancer stem cell regulation

Casey Droscha, 2011-present Thesis: Examining the role of Hrpt2 in bone mass accrual

Editorial Boards

Journal of Biological Chemistry 2003-2008 Journal of Bone and Mineral Research, 2009- Endocrinology, 2011-‘ Gene, 2011-

Ad Hoc Reviewer (since 2000)

American Journal of Human Genetics BioMedCentral – Developmental Biology Bone Cancer Epidemiology, Biomarkers, and Prevention Cancer Research Cell Communication and Signaling Cell Growth and Differentiation Current Cancer Therapy Reports Developmental Biology Developmental Dynamics Endocrine Endocrinology European Journal of Human Genetics FEBS Letters Expert Review of Endocrinology & Metabolism Human Molecular Genetics Human Mutation International Journal of Oncology Journal of the American College of Cardiology Journal of Biological Chemistry Journal of Bone and Mineral Research Journal of Cell Biology Journal of Clinical Investigation Journal of Genetics and Molecular Cancer Research Molecular and Cellular Biology Nature Nature Reviews Cancer Neoplasia PLOS One Proceedings of the National Academy of Sciences, USA Science Science Translational Medicine Trends in Genetics

Invited Presentations (since 1998)

August 1998, Cancer Genetics and Tumor Suppressor Genes Meeting, Cold Spring Harbor, NY

July 1999, Wnt Meeting, Palo Alto, California November 1999, Michigan State University Microbiology Seminar Series, East Lansing, MI December 1999, Harold Varmus 60th Birthday Symposium, Cold Spring Harbor, NY

September 2000, Calvin College Biology Department Seminar Series, Grand Rapids, MI

March 2001, Western Michigan University Biology Department Seminar Series, Kalamazoo, MI April 2001, Carroll College Biology Department Seminar Series, Waukesha, WI October 2001, Biology Department Seminar Series, Holland, MI

March 2002, NIDCR Seminar Series, National Institutes of Health, Bethesda, MD October 2002, Grand Valley State University Chemistry Dept. Seminar Series, Allendale, MI

April 2003, Case Western Reserve University Dept. of Genetics Seminar Series, Cleveland, OH May 2003, University of Michigan Cancer Biology Seminar Series, Ann Arbor, MI September 2003, Michigan State University Veterinary School Seminar Series, East Lansing, MI November 2003, UCSF Cancer Center Seminar Series, San Francisco, CA

February 2004, UAB Department Seminar Series, Birmingham, AL August 2004, University of Wisconsin Department of Oncology Seminar Series, Madison, WI October 2004, Plenary Oral Presentation, ASBMR Annual Meeting, Seattle, WA October 2004, Concurrent Oral Presentation, ASBMR Annual Meeting, Seattle, WA December 2004, Amgen, Thousand Oaks, CA

April 2005, NIDCR Seminar Series, National Institutes of Health, Bethesda, MD September 2005, British Society of Developmental Biology Autumn Meeting: Wnt Signaling in Development, Disease, and Cell Biology, Aberdeen, Scotland, United Kingdom October 2005, Karmanos Cancer Center Retreat, Detroit, MI

February 2006, Wayne State University School of Medicine, Department of Pathology, Detroit, MI April 2006, Advances in Mineral Metabolism/ASBMR Young Investigators’ Meeting, Snowmass, CO September 2006, Concurrent Oral Presentation, ASBMR Annual Meeting, Philadelphia, PA October 2006, Indiana University School of Medicine, Department of Orthopedics, Indianapolis, IN December 2006, Spectrum Health Orthopedic Surgery Grand Rounds, Grand Rapids, MI

April 2007, NIDCR Seminar Series, National Institutes of Health, Bethesda, MD May 2007, University of Arkansas for Medical Sciences, Little Rock, AR June 2007, International Bone and Mineral Society 17th Scientific Meeting, Montreal, Quebec September 2007, Innovative Minds in Prostate Cancer Today Meeting, Atlanta, GA October 2007, Department of Endocrinology, Mt. Sinai Medical Center, New York, NY October 2007, Department of Orthopedic Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, MA November 2007, Vanderbilt Center for Bone Biology, Nashville, TN December 2007, Biochemistry and Molecular Biology Department, University of Texas Medical Branch, Galveston, TX

June 2008, Louisiana State Health Science Center, Department of Biochemistry and Molecular Biology, New Orleans, LA August 2008, 38th Sun Valley Workshop on Skeletal Tissue Biology, Sun Valley, ID August 2008, Translational Genomics Research Institute, Phoenix, AZ September 2008, Concurrent Oral Presentation, ASBMR Annual Meeting, Montreal, Quebec October 2008, “From Genetics Research to the Practice of Genomic Medicine,” National Cancer Centre Singapore October 2008, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China November 2008, University of Iowa Carver College of Medicine, Iowa City, IA

January 2009, University of Michigan, Oral Health Sciences Seminar Series, Ann Arbor, MI February 2009, University of Alabama-Birmingham, Center for Metabolic Bone Disease Seminar Series, Birmingham, AL March 2009, MPI Research, Mattawan, MI April 2009, Eli Lilly and Company, Indianapolis, IN May 2009, Translational Genomics Research Institute Retreat, Phoenix, AZ June 2009, Wnt Meeting, Washington, DC

March 2010, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS April 2010, Hospital for Special Surgery, New York, NY May 2010, Southwest Michigan Innovation Center and Van Andel Institute, Collaboration is Cornerstone to Success, Grand Rapids, MI October 2010, Pathways that Modify the Bone Landscape, ASBMR Annual Meeting, Toronto, Ontario

April 2011, Department of Molecular & Cellular Biochemistry, The Ohio State University, Columbus, Ohio May 2011, 3rd Joint Meeting of European Calcified Tissue Society and the International Bone and Mineral Society, Athens, Greece June 2011, Esperion Therapeutics, Ann Arbor, Michigan November 2011, University of Michigan, Center for Organogenesis, Ann Arbor, MI November 2011, Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX December 2011, The Rolanette and Berdon Lawrence Bone Disease Program of Texas Seminar Series, Baylor College of Medicine and MD Anderson Cancer Center, Houston, TX

Committees and Service External

Permanent member, NIH Skeletal Biology Development and Disease Study Section, August 2008-June 2012

Ad hoc member, NIH Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee, October 2010.

Member, Publications Committee (ad hoc), American Society for Bone and Mineral Research, 2009-2010

Member, NCI Study Section on “Integration of Mouse Models into Human Cancer Research,” February 2009

Ad hoc member, NIH Skeletal Biology Structure and Regeneration Study Section, June 2005, June 2006, and June 2007. Washington, DC.

Ad hoc member, NIH Skeletal Biology Development and Disease Study Section, October 2007, February 2008, and June 2008

Member, Department of Defense Prostate Cancer Research Program Grant Review Panel, Pathobiology 1 section, 2007-2009; 2011.

Member, Department of Defense Prostate Cancer Research Program Grant Review Panel, Cell Biology 2 section, 2010.

Ad hoc member, Department of Defense Prostate Cancer Research Program Grant Review Panel, Cell Biology 1 section, 2010.

Ad hoc member, Department of Defense Prostate Cancer Research Program Grant Review Panel, Cell Biology, 2009.

Abstract Reviewer for the European Calcified Tissue Society 37th European Symposium on Calcified Tissues, 2010-11.

Abstract Reviewer for American Society of Bone and Mineral Research Annual Meeting, 2007-2009.

Category Chair, American Society of Bone and Mineral Research Annual Meeting (Cancer and Bone) 2009 and 2011.

Grant Reviewer, AIRC-Italian Association for Cancer Research, 2009-2011.

Grant Reviewer, Council UK, 2009

Member, California Breast Cancer Research Program Grant Review Panel, Pathogenesis Section, 2003- 2006

Reviewer, National Osteoporosis Foundation Grant Program, 2007

Reviewer, American Society of Bone and Mineral Research Bridge Funding Research Grant Program, 2008-2009

Reviewer, Broad Medical Research Inflammatory Bowel Disease Grant Program, 2003 & 2005

Reviewer, University of Melbourne Doctoral Candidate Thesis, 2004

Grant Reviewer, Wellcome Trust Research Fellow Program, 2005

Grant Reviewer, Cancer Research UK, 2005, 2008, and 2010

Participant in National Cancer Institute Progress Review Group Roundtable for Kidney and Bladder Cancer, Preparing for Human Studies Subgroup, November 2001, Chantilly, VA.

Member, Michigan State University All University Committee on Animal Use and Care, January 2000- December 2001

PhD Thesis Committee Member for Takeshi Shimamura, Candidate for Doctoral Degree in Biological Sciences from Western Michigan University (2001-2002)

Publications

1. Zettergren, L.D., Cutlan, R., and Williams, B.O. (1991) Embryonic dorsal region compartments in B lymphopoiesis: Rana pipiens, Gallus gallus, and Mus musculus, Developmental and Comparative Immunology, 15:105S

2. Chen, J.C., Gorman, J.R., Stewart, V., Williams, B., Jacks, T., and Alt, F.W. (1993). Generation of normal lymphocyte populations from Rb-deficient ES cells. Current Biology 3(7); 405-413.

3. Jacks, T., Remington, L., Williams, B.O., Schmitt, E.M., Halachmi, S., Bronson, R.T., and Weinberg, R.A. (1994) Tumor spectrum analysis of p53-mutant mice. Current Biology 4(1): 1-7.

4. Slebos, R.J.C., Lee, M.H., Plunkett, B.S., Kessis, T.D., Williams, B.O., Jacks, T., Hedrick, L., Kastan, M.B., and Cho, K.R. (1994) p53-dependent G1 arrest involves pRB related proteins and is disrupted by the human papillomavirus 16 E7 oncoprotein. Proc. Natl. Acad. Sci. USA 91: 5320-5324.

5. Williams, B.O., Remington, L., Albert, D.M., Mukai, S., Bronson, R.T., and Jacks, T. (1994) Cooperative tumorigenic effects of germline mutations in Rb and p53. Nature Genetics 7: 480-484.

6. Williams, B.O., Schmitt, E.M., Remington, L., Bronson, R.T., Albert, D.M., Weinberg, R.A., and Jacks, T. (1994) Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences. EMBO J. 13: 4521-4529.

7. Morgenbesser, S.D., Williams, B.O., Jacks, T., and DePinho, R.A. (1994) p53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens. Nature 371: 72-74.

8. Williams, B.O., Morgenbesser, S.D., DePinho, R.A., and Jacks, T. (1995) Developmental and tumorigenic consequences of Rb and p53 mutations. Cold Spring Harbor Symp. on Quant. Biology, VolumeLIX:449-457.

9. Haas, A.L., Baboshina, O., Williams, B.O., and Schwartz, L.M., (1995) Exponential increases in ubiquitin conjugate pools accompany the developmentally programmed cell death of insect skeletal muscle, Journal Biological Chemistry 270(16):9407-9412..

10. Sah, V.P., Attardi, L.D., Mulligan, G.M., Williams, B.O., Bronson, R.T., and Jacks, T. (1995) A subset of p53-deficient female embryos develop exencephaly. Nature Genetics 10:175-180.

11. Tischler, A.S., Shih, T.S., Williams, B.O., and Jacks, T. (1995) Characterization of pheochromocytomas in a mouse strain with a targeted disruptive mutation of the Neurofibromatosis gene Nf1. Endocrine Pathology 6(4): 323-335.

12. Williams, B.O. and Jacks, T. (1996) Mechanisms of carcinogenesis and the mutant mouse. Current Opinion in Genetics and Development 6(1): 65-69.

13. Herrera, R.H., Sah, V.P., Williams, B.O., Makela, T., Weinberg, R.A., and Jacks, T. (1996) Altered cell cycle kinetics, gene expression, and G1 restriction point regulation in Rb-deficient fibroblasts. Molecular and Cellular Biology 16(5): 2402-2407.

14. Lee, M.H., Williams, B.O., Mulligan, G.J., Mukai, S., Bronson, R.T., Dyson, N., Harlow, E., and Jacks, T. (1996) Targeted disruption of p107: evidence for functional overlap with Rb. Genes and Development 10(13): 1621-1632.

15. Yamasaki, L., Bronson, R.T., Williams, B.O., Dyson, N.J., Harlow, E., and Jacks, T. (1998) Loss of E2F-1 reduces tumorigenesis and extends lifespan of Rb1(+/-). Nature Genetics 18(4): 360-364.

16. Klymkowsky, M.#, Williams, B.O.#, Barish, G., Varmus, H.E., and Vourgourakis, Y.E. (1999) Anchored plakoglobins and their interactions with the Wnt signaling components. Molecular Biology of the Cell 10: 3151-3169.

17. Fisher, G.H., Orsulic, S., Holland, E., Hively, W.P., Li, Y., Lewis, B.C., Williams, B.O., and Varmus, H.E. (1999) Development of a flexible and specific gene delivery system for production of murine tumor models. Oncogene 18: 5253-5260.

18. Zorn, A.M, Barish, G.D., Williams, B.O., Lavender, P., Klymkowsky, M.W., and Varmus, H.E. (1999) Regulation of Wnt Signaling by Sox Proteins: XSox17/ß and XSox3 interact physically with ß-Catenin and repress ß-Catenin/TCF activity. Molecular Cell 4: 487-498.

19. Barish, G.D. and Williams, B.O. (2000) The Wnt signaling pathway. In: Signaling Networks and Cell Cycle Control: The Molecular Basis of Cancer and Other Diseases, Humana Press (S. Gutkind, editor).

20. Williams, B.O.#, Barish, G.D.#, Klymkowsky, M.W., and Varmus, H.E. (2000) Comparative evaluation of ß-catenin and Plakoglobin Signaling Activity. Oncogene 19(50): 5720-5728.

21. Dunn, K.J., Williams, B.O., Li, Y., and Pavan, W.J. (2000) Neural crest directed gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development. Proc. Natl. Acad. Sci. USA 97: 10050-10055.

22. Sage, J., Mulligan, G.J., Attardi, L.D., Miller, A., Chen, S., Williams, B., Theodorou, E., and Jacks, T. (2000) Targeted disruption of the three Rb-related genes leads to loss of G1 control and immortalization. Genes and Development. 14(23): 3037-3050.

23. Lipinski, M.M., MacLeod, K.F., Williams, B.O., Mullaney, T.L., Crowley, D., and Jacks, T. (2001) Cell-autonomous and non-cell autonomous developmental functions of the retinoblastoma tumor suppressor. EMBO J. 20(13): 3402-3413.

24. Yang, H., Williams, B.O., Hinds, P., Shih, T.S., Jacks, T., Bronson, R.T., and Livingston, D.M. (2002). Tumor suppression by a severely truncated species of the retinoblastoma protein. Molecular and Cellular Biology 22(9): 3103-3110.

25. Holmen, S.L#., Salic A.#, Zylstra, C., Kirschner, M., and Williams, B.O. (2002) A Novel Set of Wnt- Frizzled Fusion Proteins Identifies Receptor Components That Activate β-catenin-Dependent Signaling. Journal of Biological Chemistry, 277(38):34727-35.

26. Takahashi, M., Yang, X., Lavery, T., Furge, K., Williams, B.O., Montag, A., Vogelzang, N., Re, G.G., Garvin, A.J., Söderhäll, S., Kagawa, S., Hazel-Martin, D., Nordenskjold, A., and Teh, B.T. (2002) Gene Expression Profiling of Favorable Wilms Tumors and Its Correlation with Clinical Features. Cancer Research, 62(22): 6598-605.

27. Bromberg-White, J.L., Webb, C.P., Patacsil, V.S., Miranti, C.K., *Williams, B.O., and Holmen, S.L. (2004). Delivery of shRNA sequences using a replication-competent avian retroviral vector. Journal of Virology 78(9): 4914-6.

*Corresponding Author

28. Spike, B., Dirlam, A. Dibling, B., Liu, H., Williams, B.O., Jacks, T., and Macleod, K.F. (2004) The Rb tumor suppressor is required for stress erythropoiesis. EMBO Journal 23(21):4319-29.

29. Holmen, S.L., Giambernardi, T.A., Zylstra, C.R., Mieras, J.M., Hess, J.F., Furge, K.A., Buckner, B.D., Resau, J.H., Ai, M., Warman, M.L., and Williams, B.O. (2004). Decreased bone density and limb deformities in mice carrying germline mutations in low-density lipoprotein related proteins 6 and 5. Journal of Bone and Mineral Research, 19(12): 2033-40

30. Robertson, S.A., Schoumans, J., Looyenga, B.D., Yuhas, J.A., Zylstra, C.R., Koeman, J.R., Swiatek, P.J., Teh, B.T., and Williams, B.O., (2005) Spectral karyotyping of sarcomas and fibroblasts derived from Ink4a/Arf-deficient mice reveals chromosomal instability in vitro. Int. J. Oncology. 26(3):629-34.

31. Qian, C.N., Knol, J., Igarashi, P., Li, F., Zylstra, U., Teh, B.T.,, and Williams, B.O. (2005) Cystic renal neoplasia following conditional inactivation of Apc in mouse renal tubular epithelium. Journal of Biological Chemistry, 280(5):3938-45. Epub 2004 Nov 18. 32. Holmen, S.L., Robertson, S.A., Zylstra, C.R., and Williams, B.O. (2005) Activation of β-catenin mediated by a Dkk1-Frizzled 5 fusion protein. Biochemical and Biophysical Research Communications, 328:533-9.

33. Holmen, S.L., Zylstra, C.R., Mukherjee, A., Sigler, R.E., Faugere, M.C., Bouxsein, M.L., Clemens, T.L., and Williams, B.O. (2005) Essential role of β-catenin in post natal bone acquisition. Journal of Biological Chemistry, 280(22):21162-8. Epub 2005 Mar 31. 34. Ai, M., Holmen, S.L., Williams, B.O., and Warman, M.L. (2005) Reduced affinity to and inhibition by DKK1 is a common mechanism by which seven different high bone mass (HBM) associated missense mutations in LRP5 affect canonical Wnt signaling. Molecular and Cellular Biology, 25(12):4946-55.

35. Holmen, S.L. and Williams, B.O. (2005) Essential Role for Ras Signaling in Glioblastoma Maintenance. Cancer Research, 65(18):8250-5.

36. Castellone, M.D., Teramoto, H., Williams, B.O., Druey, K.M., and Gutkind, J.S. (2005) Prostaglandin

E2 promotes colon cancer cell growth through a novel Gs-axin-β-catenin signaling axis. Science. 310(5753): 1504-10. Epub 2005 Nov 17.

37. Wang, P.F., Kong, D., VanBrocklin, M.W., Peng, J., Zhang, C., Potter, S.J., Gao, X., Teh, B.T., Zhang, N., *Williams, B.O., and Holmen, S.L. (2005) Simplified method for the construction of gene targeting vectors for conditional gene inactivation in mice. Transgenics 4:215-218 *Corresponding Author

36. Park, K.S., Jeon, S.H., Kim. S.E., Bahk, Y.Y., Holmen, S.L., Williams, B.O., Surh, Y.J., Chung, K.C., and Choi, K.Y. (2006) APC inhibits Ras-induced ERK pathway activation involving cellular transformation. Journal of Cell Science 119: 819-827.

39. Inoki, K., Ouyang, H., Zhu, T., Lindvall, C., Wang, Y., Stankunas, K., Wang, C., He, X., MacDougald, O.A., You, M., Williams, B.O., and Guan, K. (2006) TSC2 integrates Wnt and cellular energy signals through a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. 126(5):955-68. 40. Zhang, C., Kong, D., Tan, M.H., Pappas, D.L., Wang, P.F., Chen, J.D., Farber, L., Zhang, N., Koo, H.M., Weinreich, M., Williams, B.O., and Teh, B.T. (2006) Parafibromin inhibits cancer cell growth and causes G1 arrest. Biochemical and Biophysical Research Communications 10;350(1):17-24. Epub 2006 Sep 7. 41. Lindvall, C., Evans, N.C., Zylstra, C.R., Li, Y., Alexander, C.A., and Williams, B.O. (2006) The Wnt signaling receptor, Lrp5, is required for mammary ductal stem cell activity and tumor development in response to oncogenic Wnt effectors. Journal of Biological Chemistry 281(46):35081-7. Epub 2006 Sep 13.

42. Liu, X., Bruxvoort, K.M., Zylstra, C.R., Liu, J., Cichowski, R., Faugere, M.C., Bouxsein, M.L., Wan, C., Williams, B.O.*, and Clemens, T.L*. (2007) Lifelong accumulation of bone in mice lacking Pten in osteoblasts. Proceedings of the National Academy of Sciences 104 (7): 2259-2264. *Co-corresponding author (laboratories contributed equally) 43. Bruxvoort, K.J., Charbonneau, H.M, Giambernardi, T.A, Goolsby, J.C., Qian, C.N., Roy-Burman, P., Shaw, A.K., Berghuis, B.D. Sigler, R.E., Resau, J.H., Sullivan, R., Bushman, W., and Williams, B.O, (2007) Inactivation of Apc in the Mouse Prostate Causes Prostate Carcinoma. Cancer Research 67(6): 2490-6.

44. Young, J.J., Bromberg-White, J.L., Zylstra, C.R., Church, J.T., Boguslawski, E., Williams, B.O., and Duesbery, N.S. (2007) The LDL receptor-related proteins LRP5 and LRP6 are not required for protective antigen-mediated internalization or lethality of anthrax lethal toxin. PLOS Pathogens 2007 Mar 2;3(3):e27.

45. Lindvall, C., Bu, W., Williams, B.O., and Li, Y. (2007) Wnt signaling, stem cells, and the cellular origin of breast cancer. Stem Cell Reviews 3(2):157-68.

46. Wu, R., Hendrix, N.D., Kuick, R., Zhai, Y., Schwartz, D.R., Akyol, A., Hanash, S., Misek, D.E., Katabuchi, H., Williams, B.O., Fearon, E.R., and Cho, K.R. (2007) Mouse model of human endometrioid adenocarcinoma based on somatic defects in the Wnt/β-catenin and PI3K/Pten signaling pathways. Cancer Cell 11(4):321-33.

47. Hinoi, T., Akyol, A., Ferguson, D.O., Greenson, J.K., Williams, B.O., Cho, K.R., and Fearon, E.R. (2007) Somatic Apc inactivation and adenoma-carcinoma progression in mouse colon. Cancer Research Cancer Res. Oct 15;67(20):9721-30.

48. Wolf, J., Palmby, T.R., Gavard, J., Williams, B.O., and Gutkind, J.S. (2008) Multiple PPPS/TP motifs are required for Wnt signaling through LRP6. FEBS Letters 582(2):255-61. Epub 2007 Dec 18.

49. Shekhar, M.P.V., Tait, L., Williams, B.O., and Gerard, B. (2008) Rad6B is a positive regulator of β- catenin accumulation. Cancer Research 68(6): 1741-50.

50. Wang, P., Bowl, M.R., Bender, S., Peng, J., Farber, L., Chen, J., Ali, A., Alberts, A.S., Thakker, R.V., Williams, B.O., and Teh, B.T. (2008) Parafibromin is required for early embryonic development and survival in adult mice by regulating growth factors. Molecular and Cellular Biology 28(9):2930-40. Epub 2008 Jan 22.

51. Robinson, D.R., Zylstra, C.R., and Williams, B.O. (2008) Wnt Signaling and Prostate Cancer. Current Drug Targets 9(7):271-280.

52. Qian, Z., Chen, L., Fernald, A.A., Anastasi, J., Williams, B.O., and LeBeau, M.M. (2008) A critical role for Apc in hematopoietic stem and progenitor cell survival. Journal of Experimental Medicine 205(9):2163-75.

53. Chen, J., Futami, K., Petillo, D., Peng, J., Wang, P., Knol, J., Li, Y., Khoo, S.K., Huang, D., Qian, Cn.N., Zhao, P., Dykyma, K., Zhang, R., Cao, B., Yang, X., Furge, K.A., Williams, B.O., and Teh, B.T. (2008) Deficiency of Flcn in mouse kidney leads to development of polycystic kidneys and renal neoplasia. PLOS ONE 3(10):e3581. Epub 2008 Oct 30.

54. VanKoevering, K.K. and Williams, B.O. (2008) Transgenic Mouse Strains for Conditional Gene Deletion During Skeletal Development. IBMS BoneKEy 5(5):151-170.

55. Zylstra, C.R., Wan, C., VanKoevering, K.K, Sanders, A.K., Lindvall, C., Clemens, T.L., and Williams, B.O. (2008) Gene targeting approaches in mice: assessing the roles of LRP5 and LRP6 in osteoblasts. J. Musculoskeletal Neuronal Interactions. 8(4):291-293.

56. Williams, B.O. and Insogna, K.L. (2009) Where Wnts Went: the exploding field of Lrp5 and Lrp6 signaling in bone. Journal of Bone and Mineral Research. 24(2):171-178. Epub 2008 Dec 15.

57. Lindvall, C., Zylstra, C.R., Evans, N.E., West, R.A., Dykema, K., Furge, K., and Williams, B.O. (2009) The Wnt co-receptor Lrp6 is required for normal mammary gland development. PLOS ONE 4(6):e5813. Epub 2009 June 5.

58. Badders, N., Goel, S., Clark, R., Klos, K., Kim. S., Bafico, A., Lindvall, C., Williams, B.O., and Alexander, C. (2009) The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage . PLOS ONE 2009 Aug 12; 4(8):e6594.

59. Castilho, R.M., Squarize, C.H., Chodosh, L.A., Williams, B.O., and Gutkind, J.S. (2009) mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging. Cell Stem Cell 5(4):279-89.

60. Qian, C.N., Furge, K., Knol, J, Huang, D., Chen, J.D., Massie, A., Khoo, S.K., Buckner, B., Vandenbeldt, K., Goolsby, J.C., Resau, J.H., Camparo, P., Comperat, E., Sibony, M., Vieillefond, A., Denoux, Y., Molinie, V., Eng, C., Kort, E.J., Williams, B.O., and Teh, B.T., (2009) Activation of the PI3K/AKT pathway induces transitional cell carcinoma of the renal pelvis: Identification in human tumors and confirmation in animal models . Cancer Research 69(21): 8256-64.

61. Zhong, Z. and Williams, B.O. (2010) LRP5 (low density lipoprotein receptor-related protein 5). Atlas Genet Cytogenet Oncol Haematol. June 2010.

62. Mason, J.J. and Williams, B.O. (2010) SOST and DKK: Antagonists of LRP family signaling as targets for treating bone disease. J. Osteoporosis. Jul 1;2010. Pii:460120.

63. Coulibaly, M.O., Sietsema, D.L., Mason, J.J., Williams, B, and Jones, C.B. (2010) Recent advances in the use of P1NP as a biomarker in fracture healing. Crit. Reviews Eukaryotic Gene Expression. 20(2): 129- 39.

64. Diegel C.R., Cho, K.R., El-Naggar, A.K., Williams, B.O., and Lindvall, C. (2010) mTOR-dependent acinar cell neoplasia following inactivation of Apc and Pten in the mouse salivary gland: implications for human acinic cell carcinoma. Cancer Research 70(22): 9143-52.

65. Wan, M., Li, J., Herbst, K., Zhang, J., Yu, B., Wu, X., Qiu, T., Lei, W., Lindvall, C., Williams, B.O,. Ma, H., Zhang, F., and Cao, X. (2011) LRP6 mediates Gαs-PGCRs coupling for cAMP generation. Science Signaling. 4(164):ra15.

66. Valkenburg, K.C. and Williams, B.O. (2011) Mouse Models of Prostate Cancer. Prostate Cancer, Article ID 895238, 22 pages, doi:10.1155/2011/895238

67. Stefater, J.A., Lewkowich, I., Rao, S., Mariggi, G., Carpenter, A.C., Burr, A.R., Fan, J., Ajima, R., Molkentin, J.D., Williams, B.O., Wills-Karp, M., Pollard, J., Yamaguchi, T., Ferrara, N., Gerhardt, H., and Lang, R.A. (2011) Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in microglia. Nature 474(7352):511-5.

68. Cui, Y., Niziolek, P.J., MacDonald, B.T., Zylstra, C.R., Alenina, N., Robinson, D.R., Zhong, Z., Matthes, S., Conlon, R.A., Brommage, R., Liu, Q., Mseeh, F., Powell, D.R., Yang, Q., Zambrowicz, B., He, X., Bader, M., Williams, B.O., Warman, M.L., and Robling, A.G. (2011) Lrp5 functions in bone to regulate bone mass. Nature Medicine 17(6):684-91.

69. Valkenburg, K.C., Graveel, C.R., Zylstra-Diegel, C.R., Zhong, Z., and Williams, B.O. (2011) Wnt/B- catenin signaling in normal and cancer stem cells. 3(2):2050-79.

70. Zhong, Z., Baker, J.J., Zylstra-Diegel, C.R., and Williams, B.O. (2011) Lrp5 and Lrp6 play compensatory roles in mouse intestinal development. Journal of Cellular Biochemistry 2011 Aug 22. Doi: 10.1002/jcb.23323. Epub ahead of print.

71. Joeng, K.S., Schumacher, C., Zylstra-Diegel, C.R., Long, F., and Williams, B.O. (2011) Lrp5 and Lrp6 redundantly control skeletal development in the mouse embryo. Developmental Biology 2011 Sep 5. Epub ahead of print.

72. Li, Y., Ferris, A., Lewis, B.C., Orsulic, S., Williams, B.O., Holland, E.C., and Hughes, S.H. (2011) The RCAS/TVA somatic gene transfer method in modeling human cancer. In: Mouse Models for Cancer Research. J. Green and T. Ried (Ed.) (in press)

73. Grabinski, T., Williams, B.O., and Steensma, M. (2011) An emerging paradigm for Wnt signaling in osteosarcoma (submitted)

74. Ke, J., Zhang, C., Zylstra-Diegel, C.R., Williams, B.O., and Xu, H.E. (2011) Role of Lrp5/6 in glucagon-induced B-catenin signaling (submitted)

75. Riddle, R.C., Zylstra-Diegel, C.R., Leslie, J.M., VanKoevering, K.K., Bouxsein, M.L, Robling, A.G., Faugere, M.-C., Clemens, T.L, and Williams, B.O. (2011) The Wnt Co-Receptors Lrp5 and Lrp6 exert distinct functions in osteoblasts during postnatal bone acquisition (submitted)

76. Fortin, S.P., Ennis, M.J., Schumacher, S.A., Zylstra-Diegel, C.R., Williams, B.O., Ross, J.T.D., Winkles, J.A., Loftus, J.C., Symons, M.H., and Tran. N.L. (2011) Cdc42 and the guanine nucleotide exchange factors Ect2 and Trio modulate Fn14-Rac1-induced migration and invasion of glioblastoma cells (submitted)

77. Qian, C.N. and Williams, B.O. (2011) The induction of high endothelial venule remodeling by primary tumors does not correlate to the metastatic capability of tumor cells (submitted)

78. Regard, J.B., Zhong, Z., Williams, B.O., and Yang, Y. (2011) Wnt signaling in bone development and disease: Making stronger bones with Wnts (invited submission to Cold Spring Harbor monograph on Wnt Signaling)

79. Zhong, Z., Zylstra-Diegel, C.R.; Schumacher C.A., Baker, J.J., Carpenter, A.C., Rao, S., Yao, W., Guan, M.; Helms, J.A.; Lane, N.E.; Lang, R.A.; and Williams, B.O. (2011) Wntless/GPR177 functions in mature osteoblasts to regulate bone mass (submitted)

Patents

Mammary Stem Cell Marker United States Patent #:US 7,563,619 B2 Bart Williams, Caroline M. Alexander, Charlotta Lindvall, and Nisha McConnell Filed: May 30, 2007

Low-Density Lipoprotein Receptor 6 (LRP6) as a Mammary Stem Cell Marker and Related Methods United States Patent #:US 7,622,267 B2 Bart Williams and Charlotta Lindvall Filed: May 30, 2007

Current and Recent External Funding

NIH R01AR053293 Williams (PI) 08/10/07 – 07/31/12 National Institutes of Health (NIAMS) Analyzing the Role of Wnt Signaling in Bone Development The focus of this work is to examine the roles of Lrp5 and Lrp6 in bone development. Role: Principal Investigator (25% effort)

BC084808 Williams (PI) 02/01/09 - 01/31/12 Department of Defense Canonical Wnt Signaling as a Specific Marker of Normal and Tumorigenic Mammary Stem Cells The focus of this work is to examine whether cells with activated Wnt signaling represent a stem cell enriched fraction within the mammary gland. Role: Principal Investigator (20% effort)

R21RR024887 Williams (PI) 07/01/09 – 06/30/11 Mouse Models to Characterize the Role of Lrp6 in Metabolic Syndrome The goal of this work is to develop and characterize a mouse model to understand the role of Lrp6 mutations in metabolic syndrome. Role: Principal Investigator (20% effort)

RO1DK083350 Wan (PI) 06/01/09 – 05/31/14 PTH signaling through LRP6 National Institutes of Health (NIDDK) The goal of this work is to define molecular mechanisms by which PTH controls bone development. Role: Collaborator (5% effort)

BC062777 Resau (PI) 09/01/07 – 08/31/08 Department of Defense Intravital Imaging of Developing Breast Cancer Lesion of Defined Genomic Profile in a Mouse The major goal of this project is to determine whether rapamycin is a potential treatment for stem cell derived mammary cancers. Role: Co-Investigator

DAMD17-03-1-0031 Williams (PI) 04/01/03 - 03/31/06 U.S. Army Medical Research Acquisition Activity (DoD / CDMRP) Analysis of the Role of the Wnt/β-Catenin Pathway in Prostate Development and Tumorigenesis The major goal of this project was to test the hypothesis that alterations in β-Catenin regulation directly contribute to prostate cancer progression and the propensity of prostate cancer to metastasize to the bone. Role: Principal Investigator

GR-240 Swiatek (PI) 09/01/01 - 08/31/06 Michigan Economic Development Corporation / Michigan Life Sciences Corridor Michigan Animal Models Consortium / Mutant Mouse Repository The major goal of this project was to develop animal model core services for the State of Michigan. Role: Co-Investigator

NOF Research Grant Award Williams (PI) 09/01/03 - 08/31/04 National Osteoporosis Foundation Analyzing the Relationship of the Wnt Signaling Pathway to Osteoporosis The major goal of this project was to use conditional knockout approaches to create mice lacking genes of the Wnt signaling pathway specifically in osteoblasts. Role: Principal Investigator