Cancer Biology Training ProgramWashington University School of

MedicineSiteman Cancer Center

Lee Ratner MD PhDProgram Director

Director, Molecular Oncology

Objectives

• To train graduate and postgraduate students in interdisciplinary research relevant to cancer biology

• To provide basic scientists in depth training in diverse aspects of basic, translational, and clinical cancer research

• To foster the development of interdisciplinary collaborative undertakings

• Program is devoted entirely to training students in the PhD program or postdoctoral fellows with a PhD, not those training for or have received MD or MD PhD degrees who have other sources of support our institution and other avenues of obtaining a background in broad issues of cancer biology.

Rationale• In light of the rapid pace and complexity of basic, translational, and

clinical research, it is imperative to provide graduate and post-graduate trainees the necessary armamentarium of experimental skills and intellectual background to undertake cutting edge cancer research

• Success in an academic career pathway requires proficiency in research skills and mentored training.

• This program is closely integrated with and supported by the Siteman Cancer Center.

• Specific didactic courses and journal clubs integrates these fields with other areas of cancer research in providing trainees a broad and in-depth understanding of important issues in oncology.

• A clinical mentoring program is provided to give graduate students and post-doctoral fellows exposure to translational and clinical research approaches.

• This is the only training program at our university completed dedicated to research in cancer biology.

Program History• Initiated at Washington University with institutional funds in 2002 as a

program for training graduate students. • The program may be expanded to include postdoctoral students with

funding of the T32 application• The Siteman Cancer Center (SCC) at Washington University funded at

50% stipend level for 2 yrs each:– 8 students in 2002 – 6 additional students in 2003– 5 additional students in 2004– 5 additional students in 2005– In 2006, will provide full stipend to 3 postdocs & 4 students

• The didactic courses associated with the program have been ongoing since 1999

• The program has been interdisciplinary since its inception with students and postdoctoral fellows participating in cancer research in a wide range of fields in multiple different departments.

Cancer Biology GraduatesStudent Advisor Dept Program Thesis

2002

Andy Bredemeyer Ley Medicine Immunology GzmB & CTL

Marisa Ponpuak Weber Medicine Mol Gen ARF nucleolar dynamics

Sage Berg-Cross Marshall Biochem Chem Biology Modeling beta-turn mimetics

Suzanne Brady Weber Medicine Mol Genetics Nucleophosmin in cell cycle progression

Hiliary Luderer Longmore Medicine Mol Cell Bio Ajuba & Zyxin in mets

Jane Knisely Bu Radiology Mol Cell Bio LDL receptor protein in tumor invasion

Holly Epple Longmore Medicine Mol Cell Bio Ajuba in motility and polarity

Ellen Langer Longmore Medicine Mol Cell Bio Epithelial mesenchymal transition

2003

Julia Cordero Cagan Cell Bio Mol Cell Bio EGFR/Ras/MAPK in Drosophila

So Hee Dho Weintraub Surgery Mol Cell Bio Na-H exchanger in antineoplastic activity

Jaehong Kim Parks Medicine Mol Cell Bio Synovial sarcoma translocation in adhesion

Gwanghee Lee H Piwnica-Worms Cell Bio Mol Cell Bio CDC25 in breast cancer

Julie O’Neal Tomasson Medicine Mol Cell Bio Myc in myeloid leukemia

Jennifer Sprague Anderson Radiology Chem Biology Cu-ligands and metalloproteinases

Cancer Biology TraineesStudent Advisor Dept Program Thesis

2004

Gunjan Choudhary Ratner Medicine Mol Genetics HTLV receptor

Rachel Delston Harbour Opthamol Mol Cell Bio Ink4a and melanoma

Snehal Naik D Piwnica-Worms Radiology Mol Genetics Imaging beta catenin interactions

Ozge Uluckan Weilbaecher Medicine Mol Genetics Beta3 integrin and bone mets

Bin Zhang Milbrandt Pathology Mol Genetics Nkx3.1 target genes in prostate Ca

2005

Meghna Das Thakur Longmore Medicine Mol Genetics Lim proteins and epithelia adhesion

Shugaku Takeda Hsieh Medicine Dev Biol Taspase 1 and tumorigenesis

Yat Tang Marshall Biochem Comp Biol p53-Mdm2 peptide antagonists

Ho-Chou Tu Cheng Medicine Mol Cell Bio Regulation of Bcl2 proteins

Robert Yang Marshall Biochem Comp Biol Inhbitors of Erb signaling

Key recent program projects to SCC members

• The Genomics of Acute Myelogenous Leukemia” (PI: T Ley), funded by the NCI as a P01 project in 9/03

• “Functional Polymorphism Analysis in Drug Pathways” (PI: H McLeod) awarded by GM as a U01 project in 2001

• Washington University Molecular Imaging Center (ICMIC)” (PI: D Piwnica-Worms) was awarded by NCI in 5/02

• Biomed 21 is a 250,000 sq ft translational research facility to be located in the heart of the medical school that will add 50 new faculty members, funded by donations to the university, and to be completed 2005. The project will include a Center for Genomics and Human Genetics led by RK Wilson PhD, a Division of Clinical Sciences led by KS Polonsky MD, and a Center for Biological Imaging led by RJ Jost MD.

Factors instrumental to the success of this training program

• Superb and rapidly expanding medical school• An outstanding cancer center• Broad coverage of areas of modern cancer research• A vigorous and enthusiastic research-oriented faculty• Dedicated administrative staff• A program committee that is actively involved in student

and postdoctoral selection, mentoring, and policy formulation

• A sound financial base• A flexible, but defined program• Collegial atmosphere that support collaborative research• Outstanding students

Administrative Structure of Training Program

Theresa Waldhoff

Journal Clubs Participating in Molecular Oncology Training

Program

• Molecular & Developmental Journal Club K Kroll• Experimental Hematopoiesis Journal Club D Link• Cancer Biology Journal Club J Weber• Genetics Journal Club S

Dutcher• Molecular Virology Journal Club A Pekosz• Hematology & Oncology Journal Club P

Majerus

Clinical Mentoring Session

Clinical Mentors Goals

Medical Oncology – Breast Cancer Research

Matthew Ellis MD PhDKatherine Weilbaecher MD

1. Half day session in comprehensive breast cancer clinic2. Educate students on screening for breast cancer3. Discuss chemoprevention for breast cancer4. Understand genetic risk factors for breast cancer5. Review the molecular basis of breast cancer6. Review breast cancer endocrine treatment7. Review breast cancer targeted therapies

Radiation Oncology

Jeffrey Bradley MDJeff Michalski MD MBA

1. Introduce students to technical aspects of radiation therapy treatment planning and delivery.2. Students will have the opportunity to witness the clinical care of patients receiving radiotherapy for a variety of malignancies3. Students will be introduced to multidisciplinary aspects of cancer management4. Students will participate in interdepartmental patient management conferences and tumor boards

Gynecologic Oncology

Janet Rader MDMatthew Powell MD

1. Educate the students on the screening and treatment of gynecologic malignancies2. They will see many integrated therapies particularly in the treatment of ovarian cancer.3. The students will have exposure to the operating room, clinics and in-patient service. 4. They can participate in the weekly tumor board and evaluation of patients for clinical trials.

Oncologic Surgical Pathology

John Pfeiffer MD PhDRichard Burack MD

1. Review slides of cancer cancers with students to highlight pathologic basis of diagnosing and staging cancer2. Review immunohistochemical, FACS, gene rearrangement studies used by the pathologist

Oncologic Radiology & Nuclear Medicine

Dennis Balfe MDBarry Siegel MD

1. Review techniques of radiology, including CT, MRI, and PET scans, and nuclear medicine approaches to diagnosis and staging of cancer2. Review examples in which radiological techniques are used in monitoring therapeutic responses

Bone Marrow Transplantation

John DiPersio MD PhDRavi Vij MD

1. Clinical care and follow-up of autologous and allogeneic stem cell transplant recipients2. Molecular basis of tracking patients with hematologic malignancies3. Molecular basis of tracking chimerism, minimal residual disease and GvHD after allogeneic stem cell transplantation.4. Biology and clinical methods for stem cell mobilization and ex-vivo manipulation.5. Assessing risk of relapse, treatment related mortality and GvHD in patients who are planning allogeneic stem cell transplantation.

Surgical Oncology

Jeffrey Moley MDDavid Linehan MD

1. Introduce student to concepts and approaches in surgical oncology2. The students will have exposure to the operating room, clinics, and in-patient service3. The students will participate in the weekly tumor board and evaluation of patients for clinical trials

Genomics & Proteomics

Reid Townsend MDPhD Purpose, methodology, instrumentation, and clinical sample preparation and analysis for genomic expression, SNP, and proteomics analyses

Steering Committee Meetings

• Aug: – Review and select students and postdocs for the program– Review plans of journal clubs and clinical and translational

mentoring groups, and review plans for annual program retreat– Review internal advisory board and trainees’ evaluations of the

program • Jan:

– Review content and student critiques of journal clubs and clinical and translational mentoring groups, and plans for didactic course

– Review research progress forms for each pre- and post-doctoral student

• May: – Review content and student critiques of didactic courses – Pre- and post-doctoral student advising

Didactic Course

Proposed Schedule for 2006 CourseJan 17 – Lee Ratner - Introduction

Jan 24 – Jason Weber – Translational control in cancerJan 31 – Sheila Stewart – Senescence and Tumorigenesis

Feb 7 - Loren Michel – Mitotic CheckpointsFeb 14 - Simon Powell – Radiation Repair

Feb 21 Emily Cheng – Apoptosis and CancerFeb 28 – Ming You – Molecular Basis of Cancer Prevention

Mar 7 – Suzanne Pontow – Cytoskeleton and cancerMar 14 – Jeffrey Moley - Familial Cancer and Pre-emptive Surgery

Mar 21 - James Hsieh – Proteases and CancerMar 28 – Michael Tomasson – Tyrosine kinase inhibitors for cancerApr 4 – Matthew Walters – Chromosomal Abnormalities and Cancer

Apr 11 - Tim Graubert – Stem cell transplantation Apr 18- Jerry Linette – Cancer Vaccines

Apr 25 – Student sponsored speaker

Courses started in 1999

Alternating years – D Wilson & L Ratner (emphasis on pediatric vs adult oncology

Trainee ScheduleAverage Number of

Hours/Week

Fall Semester Year 1 Journal ClubClinical Mentoring Program

Other LecturesLaboratory Research

11 (4 hrs once per

month)1-236

Spring Semester Year 1

Molecular Basis of Cancer Course (even years)

Other LecturesLaboratory Research

1.51-236

Fall Semester Year 2 Journal ClubClinical Mentoring Program

Other LecturesLaboratory Research

11 (4 hrs once per

month)1-236

Spring Semester Year 2

Special Emphasis Pathway in Cancer Biology (odd years)

Other LecturesLaboratory Research

1.51-236

Other Educational Programs

• 7 SCC research programs have regular internal seminars or discussion groups, including – Cancer Genetics Lunchtime Seminar Series– Molecular and Development Biology Journal Club– Cancer Center Research Talks– Weekly Immunology Seminar– Weekly Signaling/Cell Cycle Series– Prevention and Control Seminar– Oncologic Imaging Seminar Series

• SCC has sponsored two major conferences in 2003 that have had national and international participation, including– Small Animal Imaging Resource Advanced Symposium– Stem Cell Symposium

• Division of Biology and Biomedical Sciences has extensive graduate training programs

• Siteman Cancer Center Basic Science Symposia