Judith S. Sebolt-Leopold, Ph.D.
Associate Research Professor, Department of Radiology
109 Zina Pitcher Place, BSRB, A502
Ann Arbor, MI 48109-2200
Office: 734 615-7326; Fax: 734 763-5447
jssl@med.umich.edu
EDUCATION AND TRAINING
09/1974-08/1980
PURDUE UNIVERSITY, W. Lafayette, IN
Ph.D. in Biological Sciences
09/1970-06/1974
WELLESLEY COLLEGE, Wellesley, MA
B.A. in Biology
ACADEMIC, ADMINISTRATIVE, AND CLINICAL APPOINTMENTS
UNIVERSITY OF MICHIGAN, Ann Arbor, MI
2011-present
Co-Director, Experimental Therapeutics Program, University of Michigan
Comprehensive Cancer Center
2009-present
Research Associate Professor, Dept. of Radiology, Molecular Imaging
Center
ONCOVERA THERAPEUTICS, INC., Ann Arbor, MI
2007-2009
Co-Founder & Chief Science Officer
PFIZER GLOBAL RESEARCH & DEVELOPMENT, Ann Arbor, MI
2005-2007
Executive Director, Mechanistic & Target Biology
2004-2005
Executive Director, Molecular Sciences & Technologies
2004
Interim Head, Inflammation Pharmacology
2003-2004
Senior Director, Inflammation Molecular Sciences
2001-2003
Director, Cancer Molecular Sciences
PARKE-DAVIS PHARMACEUTICAL RESEARCH, WARNER-LAMBERT CO., Ann Arbor, MI
2000-2001
Research Fellow
1993-2000
Associate Research Fellow
1990-1993
Sr. Research Associate
1988-1990
Research Associate
1984-1988
Senior Scientist
INDIANA UNIVERSITY SCHOOL OF MEDICINE, Indianapolis, IN
1980-1984
Laboratory for Experimental Oncology
Postdoctoral Research Associate & Instructor
Judith S. Sebolt-Leopold, Ph.D.
October 10, 2013
1
PURDUE UNIVERSITY, W. Lafayette, IN
1979-1980
NIH Predoctoral Trainee, Dept. of Biological Sciences
1974-1979
Teaching Asst. in Microbiology and Genetics
CURRENT GRANT SUPPORT
NIH P30 CA046592
Program Project PI: Wicha
Title: University of Michigan Comprehensive Cancer Center Support Grant
The core grant supports the senior leadership, programs and shared facilities of the Cancer Center. The
Center provides the organizational framework to promote interdisciplinary research through the
development of defined clinical, basic science and prevention programs in cancer research, and the
development and support of shared resources
Role: Co-Director, Experimental Therapeutics Program
06/01/2012 – 05/31/2017
(0.6 calendar)
$3,664,665
NIH R01 CA155198
PI: Leopold
Title: Design of MEK Inhibitor Regimens for the Treatment of Pancreatic Cancer
Goals: The primary goal of this proposal is to systematically investigate MEK inhibition as a strategy for
the treatment of pancreatic cancer.
04/01/2012-03/31/2017
(3.0 calendar)
$1,251,377
Medimmune, Inc. (12-PAF06715)
PI: Leopold
Title: Development of Stem Cell Biomarkers in Colorectal Cancer
Goals: This industry-sponsored grant supports comprehensive molecular and cancer stem cell
profiling of a panel of patient-derived colorectal cancer (CRC) models to better understand the
association between CRC stem cell populations and their impact on therapeutic outcome.
06/01/2012-05/31/2014
(2.4 calendar)
$269,231
UMCC
PI: Leopold
Title: Development of Personalized Combination Strategies for the Treatment of BRAF and NRAS
Mutated Melanoma
Goals: To incorporate molecular profiling into an imaging-based approach for the design of
individualized treatment strategies for melanoma.
03/06/2012-03/05/2014
(0 Calendar)
$40,000
Judith S. Sebolt-Leopold, Ph.D.
October 10, 2013
2
NIH PO1 CA085878-05A2
PI: Ross
Title: Brain Tumor Therapeutic Efficacy by Quantitative MR
Goal: The major goal of this project is to improve the overall clinical care of glioma patients using a
combination of genomicas, proteomics, bioinformatics, mouse models and functional/molecular imaging
technologies.
Role: Project 1 Co-Project Leader
07/01/2013-06/30/2018
(1.8 Calendar)
$10,160,853
PENDING GRANT SUPPORT
NIH R21 13-PAF06706
PI: Leopold
Title: Co-Targeting CDK4 and MEK for Metastatic Colorectal Cancer Therapy
Goal: The primary goal of this proposal is to systematically investigate co-targeting of CDK4 and MEK
as a combination strategy for the treatment of metastatic colorectal cancer. The overarching goal is to
generate compelling preclinical support for this experimental strategy to inform rationally designed
clinical trials in the future.
04/01/2014-03/31/2016
(2.4 Calendar)
$427,625
HONORS
1980
2003
2008
Sigma Xi
Pfizer Global R & D Michigan Manager of the Year
AACR Women in Cancer Research – Database of Distinguished Women Scientists
MEMBERSHIP TO PROFESSIONAL SOCIETIES
1989-present American Association for Cancer Research
2002-present American Society of Clinical Oncology
EDITORIAL POSITIONS AND BOARDS
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Senior Editor, Molecular Cancer Therapeutics
Editorial Board, Cancer Research
Associate Editor, Neoplasia
Cancer Today, Editorial Adviser
Medical Advisory Board, Wilex AG, Munich, Germany
Scientific Advisory Board, Deciphera Pharmaceuticals, Lawrence, KS
Judith S. Sebolt-Leopold, Ph.D.
October 10, 2013
3
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Scientific Advisory Board, Forma Therapeutics, Cambridge, MA
Reviewer for Nature, Nature Medicine, Nature Chemical Biology, Cancer Research, Molecular
Cancer Therapeutics, PNAS, Clinical Cancer Research, Oncogene, Neoplasia, Gastroenterology
INTERNAL COMMITTEE AND PEER-REVIEW SERVICES
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University of Michigan Cancer Research Committee
University of Michigan GI SPORE Clinical Applications Committee
University of Michigan Center for the Discovery of New Medicines Steering Committee
EXTERNAL
SERVICES
COMMITTEE,
ORGANIZATIONAL,
&
PEER-REVIEW
1991
Chair of Symposium: New Drugs Exploiting Tumor Physiology, International Congress
of Radiation Research
1994
Chair of Symposium: Targeting Ras for Cancer Chemotherapy; Annual Meeting of
American Assoc. for Cancer Research
1997
Chair of Poster Discussion Session: Inhibitors of Farnesyl Protein Transferase and ras
Signaling; Annual Meeting of American Assoc. for Cancer Research,
1998
Scientific Reviewer for Department of Defense Study Section, Prostate Cancer Research
Program
1999
Site Visit Reviewer for NIH, Targeting Ras in Acute Myelocytic Leukemia, MD
Anderson, Houston, TX,
2002
Moderator of Signaling Kinase Session at NCI-sponsored workshop on “Strategies for
Imaging Priority Targets”, Frankfurt, Germany.
2003
Section Chairperson, AACR Annual Meeting Program Committee
2003
Educational Session Chairperson, 2003 Annual Meeting, Washington, DC, “New
Paradigms for Tyrosine Kinase Specificity: Molecular Biology to the Clinic”
2003
Symposium Chairperson, 2003 AACR Annual Meeting, Washington, DC, “Clinical
Research: Molecular Markers of Prognosis”
2003
Session Chair, 2003 Gordon Research Conference, Molecular Therapeutics of Cancer,
Queen’s College, Oxford, UK, “Kinases and Inhibitors”
2003
Program Committee, 2003 AACR-NCI-EORTC International Conference, Boston, MA
2004
Organizer for 2004 Keystone Conference “Protein Kinases & Cancer: The Promise of
Molecular-Based Therapies”, Granlibakken Resort, Tahoe City, CA
Judith S. Sebolt-Leopold, Ph.D.
October 10, 2013
4
2004
Program Committee, 2004 AACR Annual Meeting, Orlando, FL
2004
Program Committee, 2004 AACR-NCI-EORTC International Meeting, Geneva,
Switzerland
2004
Symposium Chairperson, 2004 AACR Annual Meeting, Orlando, FL, “Experimental and
Molecular Therapeutics: Cell Signaling inhibitors”
2004
Chairperson, Session on “Molecularly Targeted Cancer Drugs”, 6th Annual Anti-Cancer
Drug Discovery & Development Summit, Philadelphia, PA
2005
2005 AACR Education Committee
2005
Organizing Committee, AACR Scientist-Survivor Program Educational Workshop
2005
Consultant to Memorial Sloan-Kettering Cancer Center, Cancer Chemotherapy Program
Reviewer
2005-07
American Association for Cancer Research, Grants Committee
2005-08
American Association for Cancer Research, Finance & Audit Committee
2006
Co-Chairperson, Program Committee, AACR International Conference on Molecular
Diagnostics in Cancer Therapeutic Development, Chicago, IL
2006
Consultant to NCI’s Translational Research Working Group
2007
Co-Chairperson, New Drugs on the Horizon Symposium, Annual Meeting of the
American Association for Cancer Research, Los Angeles, CA
2007
Program Committee & Session Chair, Molecular Diagnostics in Cancer Therapeutic
Development: Maximizing Opportunities for Personalized Treatment, Atlanta, GA
2007
Session Chair on “Emerging Kinase Targets’, AACR-NCI-EORTC International
Conference on ‘Molecular Targets and Cancer Therapeutics: Discovery, Biology, and
Clinical Applications’, San Francisco, CA
2007
Moderator of Press Conference on ‘Targets on the Horizon, AACR-NCI-EORTC
International Conference on ‘Molecular Targets and Cancer Therapeutics: Discovery,
Biology, and Clinical Applications’, San Francisco, CA
2008
Program Committee Chairperson of Experimental Therapeutics Section on Drug
Discovery, 2008 Annual Meeting of the American Association for Cancer Research
Judith S. Sebolt-Leopold, Ph.D.
October 10, 2013
5
2008
Moderator of Press Conference on ‘Drugs in the Pipeline’, 2008 Annual Meeting of the
American Association for Cancer Research, San Diego, CA
2010
Invited participant of CTSI UCSF Committee on Multicenter Clinical Trial Planning for
Costello and CFC Syndromes: The use of small molecule inhibitors for the treatment of
developmental disorders, July 8-9, 2010, UCSF, San Francisco, CA
2011
Program Committee, Experimental Therapeutics Section, 2012 Annual Meeting of the
American Association for Cancer Research, Chicago, IL
2012
Committee Member, AACR Clinical Research and Experimental Therapeutics Awards
Selection Committee
2012
Committee Member, Pancreatic Cancer Action Network-American Association for
Cancer Research Pathway to Leadership Grants Scientific Review
2012
Mentor, Professional Advancement Series Roundtable Session: “Careers in Clinical and
Translational Cancer Research”, 2012 Annual Meeting of the American Association for
Cancer Research, Chicago, IL, March 31, 2012
2012
Discussion Leader, WICR Career Mentoring Session, 2012 Annual Meeting of the
American Association for Cancer Research, Chicago, IL, April 1, 2012
2012
Working Group Member, NCI Industry-Academic-Government Collaborations for
Cancer Target Validation (H Varmus & J Doroshow, organizers), April 13, 2012
2013
Working Group Member, NCI Provocative Questions Workshop on “Understanding the
Design and Use of Combination Therapies”, April 24, 2013
2013
Expert Forum Chair, 1st Annual Expert Forum on BRAF/MEK Signaling, September,
2013 (pending)
2013-2017
Member, Developmental Therapeutics Study Section, NIH Center for Scientific Review
CONSULTANCY SERVICES
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Ambit Biosciences, La Jolla, CA
Van Andel Research Institute, Grand Rapids, MI
Compendia Biosciences, Ann Arbor, MI
LAM Treatment Alliance, Cambridge, MA
Wilex AG, Munich, Germany
Forma Therapeutics, Cambridge, MA
Prometheus Laboratories, Inc., San Diego, CA
Celgene Corporation, Summit, NJ
Judith S. Sebolt-Leopold, Ph.D.
October 10, 2013
6
EXTRAMURAL INVITED PRESENTATIONS
1. “Reversal of Resistance to Anthrapyrazoles and Anthracyclines in Multidrug Resistant Cells”,
Biochemical Modulators Advisory Group (BMAG) Meeting, NCI, July 27, 1985
2. “The Use of Cell Biology and Biochemical Pharmacology Approaches to Identify Novel
Intercalating Agents”. Antineoplastic Drug Discovery Symposium/Phase I, BMAG Meeting, Nov.
17, 1986
3. “Warner-Lambert Experience with Assays for Radiosensitivity”, NCI-DCT Workshop on
Screening of Compounds for Radiosensitizing Activity, May 11-12, 1989
4. “Drug Development Targeted Against Hypoxic Tumor Cells; Implications for Radiotherapy and
Chemotherapy”. Univ. of Michigan, Dept. of Pharmacology, January 30, 1990
5. “Cancer Drugs and Their Mode of Action”. Eastern Michigan University, Dept. of Microbiology,
November 12, 1990
6. “Enhancement of RSU 1069-Induced Cytotoxicity and DNA Damage by a Potent Inhibitor of
Poly (ADP-Ribose) Polymerase, PD 128763. Tumor Hypoxia and Spheroid Workshop, Orillia,
Ontario, July 3, 1991
7. “Design of Novel Anticancer Agents Targeted Against Hypoxic Cells”. Univ. of Toledo, Dept. of
Medicinal Chemistry, November 18, 1993
8. “Pharmaceutical Issues Important to the Development of PD 144872 (CI-1010), the R-Isomer of
RB6145”. IBC/MRC Conference on Successful Exploitation of Biomedical Research, London,
UK, March 7-8, 1994
9. “Bioreductive Drugs: A New Generation of Hypoxic Cell Radiosensitizers”. Ninth International
Symposium on Radiopharmacology, Univ. of Michigan Medical Center, June 7-10, 1995
10. “Farnesyltransferase Targeted Anticancer Drug Design: A Mechanism-Based Approach to
Molecular Oncology”. Gordon Research Conference: Enzymes, Coenzymes & Metabolic
Pathways, July 12-17, 1998
11. “A New Generation of MEK Inhibitors: Tools for In Vivo Evaluation”, Rockefeller University,
N.Y. Academy of Sciences Conference: Anti-Cancer Proteins and Drugs: Structure, Function,
and Design, November 8, 1998
12. “Signalling Antagonists as Potential Anticancer Agents”.
Pharmacy, December 9, 1998
Wayne State Univ., College of
13. “In Vivo Blockade of the MAP Kinase Pathway Inhibits Growth of Murine and Human
Tumours”. Society for Medicines Research Symposium: Protein Kinases and Therapeutic
Opportunities, Sandwich Kent, UK, March 25, 1999
Judith S. Sebolt-Leopold, Ph.D.
October 10, 2013
7
14. “Exploring the MAP Kinase Pathway by Pharmacological Intervention”. Symposium on
Mitogen-Activated Protein Kinase Signaling Cascades and Oncogenesis: Annual Meeting of
American Association for Cancer Research, San Francisco, CA, April 3, 2000
15. “MEK Inhibitors as a Pharmacological Approach to Intervention of the MAP Kinase Pathway”,
Wayne State University, Department of Pharmacology, March 30, 2001
16. “Targeting the MAP Kinase Pathway: Pharmacological Opportunities for Improved Antitumor
Therapies” Gordon Research Conference: Chemotherapy of Experimental and Clinical Cancer,
Colby-Sawyer College, New London, NH, July 15-19, 2001
17. “Targeting the MAP Kinase Pathway: Therapeutic Utility of MEK Inhibitors as Anticancer
Agents” Michigan Society of Toxicology 2001 Fall Meeting: Mechanisms of Chemicals
Designed for Selective Toxicity, October 19, 2001
18. “CI-1040: A Novel Small Molecule MEK Inhibitor with Broad Spectrum Antitumor Activity”
Plenary lecture at AACR-NCI-EORTC International Conference: Molecular Targets and Cancer
Therapeutics: Discovery, Biology, and Clinical Applications, Miami Beach, FL, October 29November 2, 2001
19. “CI-1040: A MEK Inhibitor with Potential Therapeutic Activity against Colorectal Cancer” First
Annual Opinion Leader Summit on Targeted Therapies in the Treatment of Colorectal Cancer,
Maui, Hawaii, February 13–17, 2002
20. “MEK Targeted Therapy: Lessons Learned with CI-1040” 2002 Annual Meeting of the
American Association for Cancer Research, Targeted Therapies Symposium, San Francisco, CA,
April 8, 2002
21. “The Potential of MEK Inhibitors for Anticancer Therapy”, Van Andel Research Institute, Grand
Rapids, MI, June 12, 2002
22. “Development of Therapeutics Targeting MEK”, First International Congress on Targeted
Therapies, Washington, DC, August 16, 2002
23. “Cancer Therapy Targeting the MAP Kinase Pathway: The Potential of MEK Inhibitors”, First
Annual Symposium on Anti-Receptor Signaling in Human Neoplasia, Chicago, IL, September 21,
2002
24. “Advances in the Development of New Cancer Therapies Targeting the MAP Kinase Pathway”,
Wayne State University, Detroit, MI, October 23, 2002
25. “Targeting the MAP Kinase Pathway for the Development of New Cancer Therapies”, Purdue
University, W. Lafayette, IN, October 31, 2002
Judith S. Sebolt-Leopold, Ph.D.
October 10, 2013
8
26. “The Potential of MEK Inhibitors in Molecular Targeted Therapy”, ASCO Molecular
Therapeutics Symposium, San Diego, CA, November 9, 2002
27. “Intracellular Messenger Cascades and Their Role in Cell Growth, Multiplication, Survival, and
Differentiation”, New Targets and Innovative Strategies in Cancer Treatment: a short course for
clinicians, Monte Carlo, February 8, 2003
28. “MEK Inhibition: A Viable Therapeutic Approach against Colorectal Cancer?” Second Annual
Opinion Leader Summit on Targeted Therapies in the Treatment of Colorectal Cancer, Beaver
Creek, CO, February 21, 2003
29. “Critical Issues Impacting the Design of Preclinical Combination Chemotherapy Studies for
Signaling Antagonists”, Symposium on Preclinical Models for Defining Efficacy of Drug
Combinations: Mapping the Road to the Clinic, NCI Frederick, MD, April 11, 2003
30. “The Design of Highly Selective Kinase Inhibitors: Too Much of a Good Thing?”, Plenary
lecture: AACR-NCI-EORTC International Conference on ‘Molecular Targets and Cancer
Therapeutics: Discovery, Biology, and Clinical Applications, Boston, MA, November 17-21,
2003
31. “Intervention of the MAP Kinase Pathway by Targeting MEK: CI-1040 and PD 0325901”, Royal
Society of Medicine, London, UK, February 12, 2004
32. “Intervention of the MAPK Pathway by Targeting MEK: CI-1040 and PD 0325901”,
International Conference on “Targeted Cancer Therapies: One Year of Progress”, Palais de la
Mediterranee, Nice, France, February 13-14, 2004
33. “Attractiveness of Targeting MEK for Anticancer Drug Development” Keystone Symposium on
Protein Kinases and Cancer: The Promise of Molecular-Based Therapies”, Granlibakken Resort,
Tahoe City, CA, February 26, 2004
34. “The Biological Profile of PD0325901: a Second Generation Analog of CI-1040 with Improved
Pharmaceutical Potential”, 95th Annual AACR Meeting, Orlando, FL, March 30, 2004
35. “Combination Approaches to Molecular-Targeted Therapies”, 95th Annual AACR Meeting,
Orlando, FL, March 31, 2004
36. “Developing Molecularly Targeted Cancer Drugs – The Pharma Perspective”, Given Institute of
the Univ. of Colorado, Aspen, CO, Workshop on Molecular Biology in Clinical Oncology, July 7,
2004
37. “Pharmacological Challenges in Kinase-Targeted Anticancer Drug Development”, Yale
University, Symposium on ‘Kinase Proteomics & Drug Development’, October 15, 2004
Judith S. Sebolt-Leopold, Ph.D.
October 10, 2013
9
38. “The Design of Novel Combination Regimens with Signaling Antagonists: Promising Early
Studies with the MEK Inhibitor PD0325901”, International Conference on Tumor Progression
and Therapeutic Resistance, Philadelphia, PA, November 8-9, 2004
39. “Kinase-Targeted Therapies – Empty Promises or Path to a Cure?”, 2005 Miami Nature
Biotechnology Winter Symposium on ‘Signal Transduction in Cancer’, February 6, 2005
40. “The Ras-MAP Kinase Pathway in Tumors: How Far Have We Come with Molecular-Targeted
Therapy?”, Norton Cotton Cancer Center, Dartmouth College, March 3, 2005
41. “Evolution of the MEK inhibitor PD0325901: From Discovery to Clinical Development”,
Symposium on Targeting Kinase Inhibition for Cancer Therapy, American Chemical Society
Meeting, San Diego, CA, March 16, 2005
42. “The Development of MEK Inhibitors for Molecular-Based Cancer Therapy”, CNIO Cancer
Conference on MAP Kinases & Cancer, Madrid, Spain, May 30-June 1, 2005
43. “Challenges and New Directions in Cancer Drug Discovery & Development”, AACR ScientistSurvivor Program Educational Workshop, Bethesda, MD, June 11-15, 2005
44. “Development of Novel Therapies that Target MEK Inhibitor-Responsive Tumors”, AACR
Special Conference on “Drugging the Cancer Genome: Developing Rational Combination
Therapies for Multigene Cancers”, Rancho Mirage, CA, January 25-28, 2006
45. “MEK Inhibitors: A Role for Highly Selective Agents in Development of Molecular-Targeted
Cancer Therapies”, Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC,
April 10, 2006
46. “The Central Role of Biomarkers and Pharmacodynamic Assays in the Development of the MEK
Inhibitor PD0325901”, PharmaDiscovery 2006 Conference (sponsored by Elsevier Press, Drug
Discovery Today), Bethesda North Marriott Hotel & Conference Center, May 11, 2006
47. “MEK Inhibitors – A Highly Selective Approach to Therapeutic Intervention of the Ras-MAP
Kinase Pathway”, Beatson International Cancer Conference on ’24 Years of Ras and Human
Cancer’, Glasgow, Scotland, June 18-21, 2006
48. “Pharmacological Intervention of the Ras-MAP Kinase Pathway”, Cardiofaciocutaneous
Syndrome & Noonan Syndrome International Conference, Potomoc, MD, November 17-19, 2006
49. “Turning MAP Kinase Pathway Inhibitors into the Real Deal: What’s Left to Do?”, Educational
Session on ‘The Ras Pathway: From Cancer Biology to Translational Opportunities’, Annual
Meeting of the American Association for Cancer Research, Los Angeles, CA, April 14, 2007
50. “The Central Role of Translational Biomarkers in Development of Molecular-Targeted Cancer
Therapies”, Days of Molecular Medicine 2007, Conference on Emerging Technologies & Cancer
Biology, Cambridge, MA, May 22-24, 2007
Judith S. Sebolt-Leopold, Ph.D.
October 10, 2013
10
51. “MEK Inhibitors: A Personalized Medicine Approach for Targeting Aberrant MAP Kinase
Signaling”, ‘25 Years of Ras’ session, Annual Conference of UK National Cancer Research,
Birmingham, UK, September 30-October 5, 2007
52. “Targeting MEK for the Development of Cancer Therapeutics Directed Against the RAS-MAP
Kinase Pathway”, UCB-Celltech, Slough, Berkshire, UK, November 28, 2007.
53. “Role of Translational Biology in MEK Inhibitor Development”, Cell Signaling and Novel
Cancer Therapeutics Conference, Royal Society of Medicine, London, UK, November 29-30,
2007
54. “The Evolution of Cancer Drugs from Kinase Inhibitors”, Meet-the-Expert Session, Annual
Meeting of the American for Cancer Research, San Diego, CA, April 13-16, 2008
55. “Development of MEK Inhibitors for Pharmacological Intervention of the RAS-MAP Kinase
Pathway”, Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back,
Berkeley, CA, August 1-2, 2009.
56. “Validation of MEK as a Target for the Treatment of Pancreatic Cancer”, Towards Personalized
Cancer Medicine, CosmoCaixa, Barcelona, Spain, May 19-21, 2010.
57. “Cancer Drug Discovery – A Long and Bumpy Road”, Indian Institute of Science Alumni
Association of North America, Midwest Chapter, University of Michigan, Ann Arbor, MI, June
19, 2010
58. “Why Drug Development Fails”, 2012 AACR Translational Cancer Research for Basic Scientists
Workshop, Boston, MA, November 30, 2012
INTRAMURAL INVITED PRESENTATIONS
1. “Advances and Challenges in Targeting the MAP Kinase Pathway in Melanoma”, Cutaneous
Oncology Program, University of Michigan Medical School, Ann Arbor, MI, April 16, 2012
2. “Discovery & Development of MEK Inhibitors: A Case History”, Cancer Biology 554 lecture,
March 29, 2012
3. “Challenges of Cancer Drug Development: How Can Imaging Help?” Radiology Grand Rounds
lecture, October 3, 2012
4. “Optimization of MEK Inhibitor-Based Strategies for the Treatment of KRAS Mutant Cancers”,
Department of Pharmacology, September 18, 2013
5. “The Evolution of MEK Inhibitors from Early Discovery to Regulatory Approval and Beyond”,
CMB/Genetics Training Program, Fall 2013 Short Course, October 1, 2013
Judith S. Sebolt-Leopold, Ph.D.
October 10, 2013
11
PATENTS
06/09/1998
Substituted Tetra- and Pentapeptide Inhibitors of Protein:farnesyl Transferase.
Gary Bolton, Alfred Campbell, Richard Gowan, John Hodges, Donald Hupe,
Daniele Leonard, Tomi Sawyer, Judith Sebolt-Leopold, Francis Tinney.
US5763577.
10/09/2001
Histidine-(N-Benzyl Glycinamide) Inhibitors of Protein Farnesyl Transferase.
Ellen Dobrusin, Annette Doherty, James Kaltenbronn, Daniele Leonard, Dennis
McNamara, Judith Sebolt-Leopold, Kevon Schuler. US6300501.
12/10/2002
Combinations of Protein Farnesyltransferase and HMG CoA Reductase Inhibitors
and Their Use to Treat Cancer. Judith Leopold and Roger Newton. US6492410.
BIBLIOGRAPHY
Peer- Reviewed Publications
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Aoki, T., J. Sebolt, and G. Weber. In vivo inactivation by acivicin of carbamoyl-phosphate
synthetase II in rat hepatoma. Biochem. Pharmacol. 31, 927-932 (1982)
Weber, G., N. Prajda, M.S. Lui, J.E. Denton, T. Aoki, J. Sebolt, Y.-S. Zhen, M.E. Burt, M.A.
Faderan, and M.A. Reardon. Multienzyme-targeted chemotherapy by acivicin and actinomycin.
Advan. Enzyme Regul. 20, 75-96 (1982)
Denton, J.E., M.S. Lui, T. Aoki, J. Sebolt, E. Takeda, J.N. Eble, J.L. Glover, and G. Weber.
Enzymology of pyrimidine and carbohydrate metabolism in human colon carcinomas. Cancer
Res. 42, 1176-1183 (1982)
Denton, J.E., M.S. Lui, T. Aoki, J. Sebolt, and G. Weber. Rapid in vivo inactivation by acivicin
of CTP synthetase, carbamoyl-phosphate synthetase II, and amidophospho-ribosyltransferase in
hepatoma. Life Sciences 30, 1073-1080 (1982)
Sebolt, J.S. and G. Weber. Negative correlation of L-glutamine concentrations with
proliferation rate in rat heptomas. Life Sciences 34, 301-306 (1984)
Weber, G., M.S. Lui, J.S. Sebolt, and M.A. Faderan. “Molecular targets of anti-glutamine
therapy with acivicin in cancer cells” in Glutamine Metabolism in Mammalian Tissues, pp. 278291, Haussinger, D. and H. Sies, eds., Springer-Verlag (1984)
Sebolt, J.S., T. Aoki, J.N. Eble, J.L. Glover, and G. Weber. Inactivation by acivicin of
carbamoyl-phosphate synthetase II in human colon carcinoma. Biochem. Pharmacol., 34, 97100 (1985)
Jackson, R.C., D.W. Fry, W.R. Leopold, J.S. Sebolt, W.D. Klohs, H.D.H. Showalter, L.M.
Werbel, and E.F. Elslager. “Biochemical pharmacology and experimental chemotherapy studies
with the anthrapyrazole CI-937, a synthetic intercalating agent with broad-spectrum murine
anticancer activity” in Recent Adv. Chemother., pp. 568-569, Isigamic, J., ed., U. Tokyo Press,
Tokyo (1985)
Roberts, B.J., K.L. Hamelehle, J.S. Sebolt, and W.R. Leopold. In vivo and in vitro anticancer
activity of the structurally novel and highly potent antibiotics CI-940 and its hydroxy analogy
(PD 114,721). Cancer Chemother. Pharmacol., 16, 95-101 (1986)
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Sebolt, J.S., S.V. Scavone, C.D. Pinter, K.L. Hamelehle, D.D. Von Hoff, and RC. Jackson.
Pyrazoloacridines, a new class of anticancer agents with selectivity against solid tumors in vitro.
Cancer Res., 47, 4299-4304 (1987)
Sebolt, J.S., M. Havlick, J. Nelson, W. Leopold, and R. Jackson. Activity of the
pyrazoloacridines against multidrug resistant tumor cells. Cancer Chemother. Pharmacol., 24,
219-224 (1989)
Jackson, R.C., J.S. Sebolt, J.L. Shillis, and W.R. Leopold. The pyrazoloacridines: approaches to
the development of a carcinoma-selective cytotoxic agent. Cancer Investigations, 8, 39-47
(1990)
Arundel-Suto, C.M., S.V. Scavone, W.R. Turner, M.J. Suto, and J.S. Sebolt-Leopold. Effects
of PD 128763, a new potent inhibitor of poly (ADP-ribose) polymerase, on x-ray induced
cellular recovery processes in Chinese hamster V79 cells. Radiation Research 126, 367-371
(1991).
Sebolt-Leopold, J.S. and S.V. Scavone. Enhancement of alkylating agent activity in vitro by
PD 128763, a potent poly(ADP-ribose) polymerase inhibitor. Int. J. Radiat. Oncol. Biol. Phys.
22, 619-621 (1992)
Sebolt-Leopold, J.S., P.W. Vincent, K.A. Beningo, W.L. Elliott, W.R. Leopold, T.G. Heffner,
J.N. Wiley, M.A., Stier, and M.J. Suto. Pharmacologic/pharmacokinetic evaluation of emesis
induced by analogs of RSU1069 and its control by antiemetic agents. Int. J. Radiat. Oncol. Biol.
Phys. 22, 549-551 (1992)
Cole, S., I.J. Stratford, E.M. Fielden, G.E. Adams, W. Leopold, W. Elliott, M. Suto, and J.
Sebolt-Leopold. Dual function nitroimidazoles less toxic than RSU1069: selection of candidate
drugs for clinical trial (RB6145 and/or PD130908). Int. J. Radiat. Oncol. Biol. Phys. 22, 545548 (1992)
Suto, M.J., W.R. Turner, C.M. Arundel-Suto, L.M. Werbel, and J.S. Sebolt-Leopold.
Dihydroisoquinolinones: the design and synthesis of a new series of potent inhibitors of poly
(ADP-ribose) polymerase. Anticancer Drug Design 7, 107-117 (1991)
Suto, M.J., M.A. Stier, L.M. Werbel, C.M. Arundel-Suto, W.R. Leopold, W.L. Elliott, and J.S.
Sebolt-Leopold.
A new class of analogs of the bifunctional radiosensitizer -[(1aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanol (RSU1069): the cycloalkylaziridines. J. Med.
Chem. 34, 2484-2488 (1991)
Suto, M.J., M.A. Stier, T.R. Winters, W.R. Turner, C.D. Pinter, W.L. Elliott, and J.S. SeboltLeopold. Synthesis and evaluation of a series of 3,5-disubstituted benzisoxazole-4,7-diones.
Potent radiosensitizers in vitro. J. Med. Chem. 34, 3290-3294 (1991)
Horwitz, J.P., I. Massova, T. Wiese, T.H. Corbett, J.S. Sebolt-Leopold, D.B. Capps, and W.R.
Leopold. Comparative molecular field analysis of in vitro growth inhibition of L1210 and HCT8 cells by some pyrazoloacridines. J. Med. Chem. 36, 3511-3616 (1993)
Bolton, G.L., Sebolt-Leopold, J.S., and J.C. Hodges. “Ras oncogene directed approaches in
cancer chemotherapy” in Annual Reports in Medicinal Chemistry, 29, 165-174 (1994)
Sebolt-Leopold, J.S. Bioreductive Drugs: A new generation of hypoxic cell radiosenstizers.
Quarterly J. Nuclear Med. 39, 44 (1995)
Corbett, T., Valeriote, F., LoRusso, P., Polin, L., Panchapor, C., Pugh, S., White, K., Knight, J.,
Demichik, L., Jones, J., Lowichik, N., Biernat, L., Foster, B., Wozniak, A., Lisow, L.,
Valdivieso, M., Baker, L., Leopold, W., Sebolt, J., Bissery, M.C., Mattes, K., Dzubow, J., Rake,
J., Perni, R., Wentland, M., Coughlin, S., Shaw, J.M., Liversidge, G., Brunol, J., Moore, R.,
Judith S. Sebolt-Leopold, Ph.D.
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Patterson, G. Tumor models and the discovery and secondary evaluation of solid tumor active
agents. Int. J. Pharmcognosy 33, 1-21 (1995)
Leonard, D.M., Eaton, S.R., Sawyer, T.K., Doherty, A.M., Bolton, G., Hodges, J., Scholten, J.,
Gowan, R., and J.S. Sebolt-Leopold. Structure-activity relationships of cysteine-lacking peptide
derivatives that inhibit Ras farnesyltransferase. Pept. 1994, Proc. European Peptide Symposium,
23rd; Maia, H.L.S., ed. ESCOM: Leiden, Netherlands, pp. 658-659 (1995)
Scholten, J.D., K. Zimmerman, G.M. Oxender, J.S. Sebolt-Leopold, R. Gowan, D. Leonard, and
D. Hupe. Inhibitors of farnesyl:protein transferase: a possible cancer chemotherapeutic. In:
Structure-based and Mechanism-based Drug Design and Drug Action”, Bioorganic & Medicinal
Chemistry, (R. Silverman, ed.), Pergamon Press 4, 1537-1543 (1996)
Scholten, J.D., K. Zimmerman, M.G. Oxender, D. Leonard, J. Sebolt-Leopold, R. Gowan, and
D.J. Hupe. Farnesyl protein transferase: Increased inhibition due to anionic synergism, J. Biol.
Chem., 272, 18077-18081 (1997)
Leonard, D.M., K.R. Shuler, C.J. Poulter, S.R. Eaton, T.K. Sawyer, J.C. Hodges, T.Z Su, J.D.
Scholten, R.C. Gowan, J.S. Sebolt-Leopold, and A.M. Doherty. Structure-activity relationships
of cysteine-lacking pentapeptide derivatives that inhibit ras farnesyltransferase. J. Med. Chem.
40, 192-200 (1997)
McNamara, D., E. Dobrusin, D.M. Leonard, K.R. Shuler, J.S. Kaltenbronn, J. Quin, S. Bur, C.E.
Thomas, A.M. Doherty, J.D. Scholten, K.K. Zimmerman, B.S. Gibbs, R.C. Gowan, M.P. Latash,
W.R. Leopold, S.A. Przybranowski and J.S. Sebolt-Leopold. C-terminal modifications of
histidyl-(N-benzylglycinamides) to give improved inhibition of ras farnesyltransferase, cellular
activity, and anticancer activity in mice. J. Med. Chem. 40, 3319-3322 (1997)
Adjei, A., M. Charron, E. Rowinsky, P.A. Svingen, J. Sebolt-Leopold, J. Miller, J.M. Reid,
M.M. Ames, and S.H. Kaufmann. Effect of pyrazoloacridine (NSC 366140) on DNA
topoisomerases I and II: prevention of cleavable complex formation. Clin. Cancer Res. 4, 683691 (1998)
Gelb, M.H., J.D., Scholten, and J.S. Sebolt-Leopold. “Protein prenylation: from discovery to
prospects for cancer treatment” In: Current Opinion in Chemical Biology 2, 40-48 (1998)
Eummer, J.T., B.S. Gibbs, T.J. Zahn, J.S. Sebolt-Leopold, and R.A. Gibbs. Novel limonene
phosphonate and farnesyldiphosphate analogues: design, synthesis, and evaluation as potential
protein farnesyl transferase inhibitors. Bioorganic & Medicinal Chemistry 7, 241-250 (1999)
Leonard, D.M., Shuler, K.R., McNamara, D., Bolton, G.L., Scholten, J.D., Zimmerman, K.,
Sebolt-Leopold, J.S., Gowan, R.C., Latash, M., Przybranowski, S., Leopold, W.R., and
Doherty, A.M. Design of peptidomimetic Ras farnesyltransferase inhibitors from a pentapeptide
lead. Proc. European Peptide Symposium, 24th; R. Ramage and R. Epton, eds., Mayflower
Scientific, Ltd: Kingswingford, UK; pp. 79-82 (1998)
Doherty, A.M., Cody, W.L., Leonard, D.M., Creswell, M., Bolton, G.L., McNamara, D., Eaton,
S.R., Shuler, K.R., Scholten, J., Sebolt-Leopold, J.S., and R.L. Panek. Signaling approaches to
inhibition of cellular proliferation. Peptides: Biol. Chem., Proc. Chinese Peptide symposium,
4th, 1996; Xu, X.-J., Ye, Y.-H., Tam, J.P., eds; Kluwer, Dordrecht, Netherlands; pp. 35-36
(1998)
Gibbs, B.S., T.J. Zahn, Y.Q. Mu, J.S. Sebolt-Leopold, and R. Gibbs. Novel farnesol derivatives
as inhibitors of ras protein function – a unique potential chemotherapeutic mechanism. J. Med.
Chem., 42, 3800-3808 (1999)
Sebolt-Leopold, J.S., D.T. Dudley, R. Herrera, K. Van Becelaere, A. Wiland, R.C. Gowan, H.
Tecle, S. Barrett, A. Bridges, S. Przybranowski, W.R. Leopold, and A.R. Saltiel. Blockade of
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the MAP kinase pathway suppresses growth of colon tumors in vivo. Nature Medicine 5, 810816 (1999)
Leonard D. and J.S. Sebolt-Leopold. “Ras farnesyltransferse inhibitors” In: Drugs of the
Future (J.R. Prous, ed.), 24, 1099-1106 (1999)
Sebolt-Leopold, J.S. “Development of anticancer drugs targeting the MAP kinase pathway” In:
Oncogene 19, 6594-6599 (2000)
Gibbs, R.A., T.J. Zahn, and J.S. Sebolt-Leopold. Non-peptidic prenyltransferase inhibitors:
diverse structural classes and surprising anti-cancer mechanisms. Curr. Med. Chem. 8, 14371465 (2001)
Herrera, R. and J.S. Sebolt-Leopold. “Unraveling the complexities of the Raf/MAP kinase
pathway for pharmacological intervention” Trends in Molecular Medicine, 8, S27-S31 (2002)
Allen, L.F., J. Sebolt-Leopold, and M. Meyer. CI-1040 (PD184352), a targeted signal
transduction inhibitor of MEK (MAPKK), Seminars in Oncology (5 Suppl 16): 105-16 (2003)
Meng, X.W., J. Chandra, K. Van Becelaere, D. Loegering, T. Kottke, S.D. Gore, J.E. Karp, J.
Sebolt-Leopold, and S.H. Kaufmann. Central role of Fas-associated death domain protein in
apoptosis induction by the mitogen-activated protein kinase kinase inhibitor CI-1040
(PD184352) in acute lymphocytic leukemia cells in vitro. J. Biol. Chem. 278, 47326-39 (2003)
Sebolt-Leopold J.S., K. Van Becelaere, K. Hook, and R. Herrera. “Biomarker assays for
phosphorylated MAP kinase: their utility for measurement of MEK inhibition. Methods in
Molecular Medicine, 85, 31-38 (2003)
Wang, Y., S. J. Decker, J. Sebolt-Leopold. Knockdown of Chk1, Wee1 and Myt1 by RNA
interference abrogates G(2) checkpoint and induces apoptosis. Cancer Biol. Ther. 3, 305-13
(2004)
Rinehart, J., A.A. Adjei, P.M. LoRusso, D. Waterhouse, J.R. Hecht, R.B. Natale, O. Hamid, M.
Varterasian, P. Asbury, E.P. Kaldjian, S. Gulyas, D.Y. Mitchell, R. Herrera, J.S. SeboltLeopold, and M.B. Meyer. Multicenter phase II study of the oral MEK inhibitor, CI-1040 in
patients with advanced nonsmall-cell lung, breast, colon and pancreatic cancer. J. Clin. Oncol.,
22, 4456-4462 (2004)
Ohren, J.F., H. Chen, A. Pavlovsky, C. Whitehead, E. Zhang, P. Kuffa, C. Yan, P. McConnell,
C. Spessard, C. Banotai, W.T. Mueller, A. Delaney, C. Omer, J. Sebolt-Leopold, D.T. Dudley,
I.K. Leung, C. Flamme, J. Warmus, M. Kaufman, S. Barrett, H. Tecle, and C.A. Hasemann.
Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel non-competitive
kinase inhibition. Nature Struct. Mol. Biol., 11, 1192-1197 (2004)
Sebolt-Leopold, J.S. “MEK inhibitors: a therapeutic approach to targeting the Ras-MAP kinase
pathway in tumors” Curr. Pharm. Design, 10, 1907-1914 (2004)
Sebolt-Leopold, J.S. and R. Herrera. “Targeting the mitogen-activated protein kinase cascade
to treat cancer”. Nature Reviews – Cancer, 4, 937-947 (2004)
Wang, Y., K. Van Becelaere, P. Jiang, S. Przybranowski, C. Omer, and J.S. Sebolt-Leopold. A
role for K-ras in conferring resistance to the MEK inhibitor CI-1040. Neoplasia, 7, 336-347
(2005)
Ricciardi, M.R., T. McQueen, D. Chism, M. Milella, E. Estey, E.S. Kaldjian, J.S. SeboltLeopold, M. Konopleva, and M. Andreef. Quantitative single cell determination of ERK
phosphorylation and regulation in relapsed and refractory primary acute myeloid leukemia.
Leukemia 19, 1543-1549 (2005)
Lorusso, P.M., A.A. Adjei, M. Varterasian, S. Gadgeel, J. Reid, D.Y. Mitchell, L. Hanson, P.
DeLuca, L. Bruzek, J. Piens, P. Asbury, K. Van Becelaere, R. Herrera, J.S. Sebolt-Leopold, and
Judith S. Sebolt-Leopold, Ph.D.
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M.B. Meyer. Phase 1 and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients
with advanced malignancies. J. Clin. Oncol., 23, 5281-5293 (2005)
Solit, D.B., L.A. Garraway, C.A. Pratilas, A. Sawai, G. Getz, A. Basso, Q. Ye., J.M. Lobo, Y.
She, I. Osman, T.R. Golub, J. Sebolt-Leopold, W.R. Sellers, and N. Rosen. BRAF mutation
predicts sensitivity to MEK inhibition. Nature, 439, 358-362 (2006)
Klein, P.J., C.M. Schmidt, C.A. Wiesenauer, E., J.N. Choi, E.A. Gage, M.T. Yip-Schneider, E.A.
Wiebke, Y. Wang, C. Omer, and J.S. Sebolt-Leopold. The effects of a novel MEK inhibitor
PD184161 on MEK-ERK signaling and growth in human liver carcinoma. Neoplasia, 8, 1-8
(2006)
Ohren, J.F. and J.S. Sebolt-Leopold. “Inhibitors of Bcr-abl… breaking new ground again”
Nature Chemical Biology (News & Views), 2, 63-64 (2006)
Sebolt-Leopold, J.S. and J.M. English. “Mechanisms of drug inhibition of signaling
molecules”. Nature, 441, 457-462 (2006)
Solit, D.B., E. Santos, C.A. Pratilas, J. Lobo, M. Moroz, S. Cai, R. Blasberg, J. Sebolt-Leopold,
S. Larson, and N. Rosen. 3’-deoxy-3’-[18F]fluorothymidine positron emission tomography is a
sensitive method for imaging the response of BRAF-dependent tumors to MEK inhibition.
Cancer Res., 67,11463-9 (2007)
Spicer, J.A., G.W. Rewcastle, M.D. Kaufman, S.L. Black, M.S. Plummer, W.A. Denny, J. 3rd
Quin, A.B. Shahripour, S.D. Barrett, C.E. Whitehead, J.B. Milbank, J.F.Ohren, R.C. Gowan, C.
Omer, H.S. Camp, N. Esmaeil, K. Moore, J.S. Sebolt-Leopold, S. Przybranowski, R.L
Merriman, D.F. Ortwine, J.S. Warmus, C.M. Flamme, A.G. Pavlovsky, and H. Tecle. 4-Anilino5-carboxamido-2-pyridone derivatives as noncompetitive inhibitors of mitogen-activated protein
kinase kinase. J. Med. Chem., 50,5090-102 (2007)
Wentz, S.C., H. Wu, M.T. Yip-Schneider, M. Hennig, P.J. Klein, J. Sebolt-Leopold, and C.M.
Schmidt. Targeting MEK is effective chemoprevention of hepatocellular carcinoma in TGFalpha-transgenic mice. J. Gastrointest. Surg. 12,30-7 (2008)
Holcomb, B., M.T. Yip-Schneider, J.M. Matos, J. Dixon, J. Kennard, J. Mahomed, R.
Shanmugam, J. Sebolt-Leopold, and C.M. Schmidt. Pancreatic cancer cell genetics and
signaling response to treatment correlate with efficacy of gemcitabine-based molecular targeting
strategies. J Gastrointest Surg. 12,288-96 (2008)
Haigis, K.M.,D.R. Kendall, Y. Wang, A. Cheung, M.C. Haigis, J.N. Glickman, M. NiwaKawakita, A. Sweet-Cordero, J. Sebolt-Leopold, K.M. Shannon, J. Settleman, M. Giovannini,
and T. Jacks. Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation
and tumor progression in the colon. Nat Genetics 40,600-8 (2008)
Barrett S.D., A.J. Bridges, D.T. Dudley, A.R. Saltiel, J.H. Fergus, C.M. Flamme, A.M. Delaney,
M. Kaufman, S. LePage, W.R. Leopold, S.A. Przybranowski, J. Sebolt-Leopold, K. Van
Becelaere, A.M. Doherty, R.M. Kennedy, D. Marston, W.A. Howard Jr., Y. Smith, J.S. Warmus,
and H. Tecle. The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 325901.
Bioorg Med Chem. Lett. 18,6501-4 (2008)
Warmus J.S., C. Flamme, L.Y. Zhang, S. Barrett S, A. Bridges, H. Chen, R. Gowan, M.
Kaufman, J. Sebolt-Leopold, W. Leopold, R. Merriman, J. Ohren, A. Pavlovsky, S.
Przybranowski, H. Tecle, H. Valik, C. Whitehead, and E. Zhang. 2-Alkylamino- and alkoxysubstituted 2-amino-1,3,4-oxadiazoles-O-alkyl benzohydroxamate esters replacements retain the
desired inhibition and selectivity against MEK (MAP ERK kinase). Bioorg Med Chem Lett.
18,6171-4 (2008)
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Sebolt-Leopold, J.S. “Advances in the Development of Cancer Therapeutics Directed Against
the RAS-MAP Kinase Pathway” Clin. Cancer Res., 14, 3651-3658 (2008)
Lauchle J.O., D. Kim, D.T. Le, K. Akagi, M. Crone M, K. Krisman, K. Warner, J.M. Bonifas, Q.
Li, K.M. Coakley, E. Diaz-Flores, M. Gorman, S. Przybranowski, M. Tran, S.C. Kogan, J.P.
Roose, N.G. Copeland, N.A. Jenkins, L. Parada, L. Wolff, J.S. Sebolt-Leopold, and K.
Shannon. Response and resistance to MEK inhibition in leukaemias initiated by hyperactive Ras.
Nature 461,411-414 (2009)
Rauen K.A., L. Schoyer, F. McCormick, A.E. Lin, J.E. Allanson, D.A. Stevenson, K.W. Gripp,
G. Neri, J.C. Carey, E. Legius, M. Tartaglia, S. Schubbert, A.E. Roberts, B.D. Gelb, K. Shannon,
D.H. Gutmann, M. McMahon, C. Guerra, J.A. Fagin, B. Yu, Y. Aoki, B.G. Neel, A. Balmain,
R.R. Drake, G.P. Nolan, M. Zenker, G. Bollag, J. Sebolt-Leopold, J.B. Gibbs, A.J. Silva, E.E.
Patton, D.H. Viskochil, M.W. Kieran, B.R. Korf, R.J. Hagerman, R.J. Packer, and T. Melese.
Proceedings from the 2009 genetic syndromes of the Ras/MAPK pathway: From bedside to
bench and back. Am. J. Med. Genet. A. 152A,4-24 (2010)
Rauen KA, Banerjee A, Bishop WR, Lauchle JO, McCormick F, McMahon M, Melese T,
Munster PN, Nadaf S, Packer RJ, Sebolt-Leopold J, Viskochil DH. Costello and cardio-faciocutaneous syndromes: Moving toward clinical trials in RASopathies. Am J Med Genet C Semin
Med Genet. 157, 136-46 (2011)
Galbán CJ, Chenevert TL, Meyer CR, Tsien C, Lawrence TS, Hamstra DA, Junck L, Sundgren
PC, Johnson TD, Galbán S, Sebolt-Leopold JS, Rehemtulla A, Ross BD. Prospective analysis of
parametric response map-derived MRI biomarkers: identification of early and distinct glioma
response patterns not predicted by standard radiographic assessment. Clin Cancer Res. 17, 475160 (2011)
Gioeli D, Wunderlich W, Sebolt-Leopold J, Bekiranov S, Wulfkuhle JD, Petricoin EF 3rd,
Conaway MR, Weber MJ. Compensatory pathways induced by MEK inhibition are effective
drug targets for combination therapy against castration resistant prostate cancer. Mol Cancer
Ther. 10:1581-90 (2011)
Williams TM, Flecha AR, Ram A, Galban S, Galban CJ, Ross BD, Rehemtulla A, SeboltLeopold JS. Co-targeting MAPK and PI3K signaling with concurrent radiotherapy as a strategy
for the treatment of pancreatic cancer. Mol Cancer Ther. 11:1193-202 (2012)
Hoff BA, Bhojani MS, Rudge J, Chenevert TL, Meyer CR, Galbán S, Johnson TD, Leopold JS,
Rehemtulla A, Ross BD, Galbán CJ. DCE and DW-MRI monitoring of vascular disruption
following VEGF-Trap treatment of a rat glioma model. NMR Biomed. 25:935-42 (2012)
Galbán S, Lemasson B, Williams TM, Li F, Heist KA, Johnson TD, Leopold JS, Chenevert TL,
Lawrence TS, Rehemtulla A, Mikkelsen T, Holland EC, Galbán CJ, and Ross BD. DW-MRI as a
biomarker to compare therapeutic outcomes in radiotherapy regimens incorporating
temozolomide or gemcitabine in glioblastoma. PLoS One 7(4):e35857. Epub Apr 20 (2012)
Collins, M, Yan W, Sebolt-Leopold, J, and Pasca di Magliano M. MAPK-dependent
dedifferentiation of acinar cells is required for pancreatic carcinogenesis, submitted (2013)
Book Chapters
1.
Leopold, W.R. and J.S. Sebolt-Leopold, “Chemical approaches to improved radiotherapy”. In:
Cytotoxic Anticancer Drugs: Models and Concepts for Drug Discovery and Development,
Kluwer Academic Publishers (1992), pp. 179-196.
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Sebolt-Leopold, J.S. “A case for Ras-targeted agents as antineoplastics” In: Cancer Drug
Discovery (B. Teicher, ed.), Marcel Dekker, Inc., pp. 395-415 (1996)
Sebolt-Leopold, J.S. “The therapeutic potential of ras farnesyl transferase inhibitors” In:
Emerging Drugs: The Prospect for Improved Medicines (Volume 2) (Fitzgerald, J.D., Bowman,
W.C., Taylor, J.B., eds.), Ashley Publications, pp. 219-239 (1996)
Sebolt-Leopold, J.S. “Farnesyltransferase inhibitors: a cell signalling approach to the design of
efficacious anticancer agents” In: Emerging Drugs: The Prospect for Improved Medicines
(Volume 3) (Fitzgerald, J.D., Bowman, W.C., Taylor, J.B., eds.), Ashley Publications, pp. 271277 (1998)
Sebolt-Leopold, J.S., D.M. Leonard, and W.R. Leopold. “Histidylbenzylglycinamides: a novel
class of FPP-competitive peptidic farnesyltransferase inhibitors” In: Farnesyltransferase
Inhibitors in Cancer Therapy (S.M. Sebti and A.D. Hamilton, eds.), Humana Press, pp. 103-114
(2001)
Leopold, W.R., A. Bridges, S. Decker, D. Fry, A. Kraker, and J.S. Sebolt-Leopold. “Growth
factor and signal transduction targets for cancer therapy” In: Anticancer Drug Development
(B.C. Baguley and D.G. Kerr, eds.), Academic Press, pp. 31-53 (2002)
Sebolt-Leopold, J.S., R. Herrera, and J.F. Ohren. “The mitogen activated protein kinase
pathway for molecular-targeted cancer treatment” In: Recent Results in Cancer Research,
Targeted Interference with Signal Transduction Events (B. Groner, ed.), Springer-Verlag, pp.
155-167 (2007)
Sebolt-Leopold, J.S. and A.J. Bridges. “The Road to PD0325901 and Beyond: The MEK
Inhibitor Quest”. In: Kinase Inhibitor Drugs; Wiley Series in Drug Discovery and Development
(R. Li and J.A. Stafford, eds.), John Wiley and Sons, pp. 205-227 (2009)
Sebolt-Leopold, J.S. “The Role of Translational Medicine in Optimization of Therapies
Targeting the RAS-MAP Kinase Pathway” In: Targeted Therapy of Acute Myeloid Leukemia
(M. Andreeff, ed), Springer Science, in press (2013)
Judith S. Sebolt-Leopold, Ph.D.
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