MBP 1018Y: OncologyMBP 1018Y: Oncology

Wednesdays, 10 a.m. – 12 noonWednesdays, 10 a.m. – 12 noonJanuary 12 – May 04, 2011 inclusiveJanuary 12 – May 04, 2011 inclusive

620 University Avenue, Room 7-709620 University Avenue, Room 7-709(CFIBCR Seminar Room)(CFIBCR Seminar Room)

OutlineOutline

IntroductionsIntroductions

Course Contact InformationCourse Contact Information

Significant DatesSignificant Dates

Course Overview – Goal, FormatCourse Overview – Goal, Format

Course EvaluationCourse Evaluation

Course ScheduleCourse Schedule

TutorialTutorial

Contact InformationContact Information

Course Coordinator: Dr. Brad WoutersCourse Coordinator: Dr. Brad Wouters– Room 10-116, Princess Margaret HospitalRoom 10-116, Princess Margaret Hospital– 610 University Avenue610 University Avenue– Tel: 416-581-7840Tel: 416-581-7840– E-Mail: E-Mail: bwouters@uhnresearch.ca

Teaching Assistant: Dr. Mahadeo Sukhai Teaching Assistant: Dr. Mahadeo Sukhai (Day-to-day contact person)(Day-to-day contact person)– Room 9-620, Princess Margaret HospitalRoom 9-620, Princess Margaret Hospital– 610 University Avenue610 University Avenue– Tel: 416-946-4501 x 5036Tel: 416-946-4501 x 5036– Email: Email: m.sukhai@utoronto.ca

Significant DatesSignificant Dates

January 12 - Introductory sessionJanuary 12 - Introductory session January 26 - Submission of abstract of January 26 - Submission of abstract of

thesis projectthesis project February 09 - Submission of midterm February 09 - Submission of midterm

assignmentassignment February 26 - Last date to drop Y/S February 26 - Last date to drop Y/S

courses without academic penaltycourses without academic penalty April 6 - Last sessionApril 6 - Last session April 13 - Oral presentations – part 1April 13 - Oral presentations – part 1 April 20 - Oral presentations – part 2April 20 - Oral presentations – part 2 April 27 - Oral presentations – part 3 (if April 27 - Oral presentations – part 3 (if

necessary)necessary) May 4 - Submission of final assignment May 4 - Submission of final assignment

Course GoalsCourse Goals

To expose graduate students to the concepts of To expose graduate students to the concepts of translational oncology (“from bench to translational oncology (“from bench to bedside”) through a series of seminar-type bedside”) through a series of seminar-type presentations highlighting recent advances of presentations highlighting recent advances of translational research;translational research;

And,And,

To motivate graduate students to apply the To motivate graduate students to apply the concepts of translational oncology to their own concepts of translational oncology to their own research through a series of written and oral research through a series of written and oral assignments. assignments.

Course FormatCourse Format

Didactic lecturesDidactic lectures– 12 sessions, led by experts in the 12 sessions, led by experts in the

fieldfield– Theme: Personalized medicineTheme: Personalized medicine

““Journal Clubs”Journal Clubs”– 12 sessions, held after each lecture12 sessions, held after each lecture

Independent term project – Independent term project – development and presentation of development and presentation of grant proposalgrant proposal

Class FormatClass Format

Part 1: Didactic lecture, 45-50 Part 1: Didactic lecture, 45-50 minutes in length; followed by minutes in length; followed by discussion/Q&Adiscussion/Q&A

Class discussion on 1-2 Class discussion on 1-2 papers chosen by lecturer, led papers chosen by lecturer, led by students (“Journal Club”)by students (“Journal Club”)

Course EvaluationCourse Evaluation

Participation (20%)Participation (20%)– Class attendance (if you are unable to attend Class attendance (if you are unable to attend

with reason, please notify Dr. Sukhai in with reason, please notify Dr. Sukhai in advance)advance)

– Leadership of journal clubLeadership of journal club

Midterm Assignment (15%)Midterm Assignment (15%)

Term Paper (50%)Term Paper (50%)

Oral Presentation (15%)Oral Presentation (15%)

Lecture AttendanceLecture Attendance

MANDATORYMANDATORY

If you are unable to attend (for e.g., If you are unable to attend (for e.g., ill; committee meeting; conference), ill; committee meeting; conference), please notify Dr. Sukhaiplease notify Dr. Sukhai– ““My experiment got in the way” is not My experiment got in the way” is not

an acceptable excuse (speaks to time an acceptable excuse (speaks to time management skills)management skills)

– ““I needed to finish my assignment for X I needed to finish my assignment for X course” is also not an acceptable excusecourse” is also not an acceptable excuse

Journal ClubJournal Club

All students are expected to read the assigned papers in All students are expected to read the assigned papers in advance of the classadvance of the class– Papers will be posted 1 week in advance of the lecture where Papers will be posted 1 week in advance of the lecture where

possible; this depends on when we get them from the lecturerpossible; this depends on when we get them from the lecturer

2-3 students will be assigned to lead the journal club 2-3 students will be assigned to lead the journal club discussion in classdiscussion in class– Leaders will be notified in advanceLeaders will be notified in advance

Come to the session with prepared questions and/or Come to the session with prepared questions and/or discussion topics that arise from the selected manuscriptsdiscussion topics that arise from the selected manuscripts– You are not expected to present the paper, figure-by-figure, You are not expected to present the paper, figure-by-figure,

but instead to come prepared to discuss it and its implications but instead to come prepared to discuss it and its implications to translational oncology and personalized medicineto translational oncology and personalized medicine

Be creative with the discussion period! Leaders can feel Be creative with the discussion period! Leaders can feel free to coordinate with each other and develop ways to free to coordinate with each other and develop ways to engage their fellow students and the lecturer in discussionengage their fellow students and the lecturer in discussion– A straight PPT show will be frowned uponA straight PPT show will be frowned upon

Midterm AssignmentMidterm Assignment

““Letter-of-intent”/Statement of Research Letter-of-intent”/Statement of Research InterestsInterests– 2 pages2 pages– Single spacedSingle spaced– Not including any necessary references or the title Not including any necessary references or the title

pagepage

ContentsContents– Clearly stated research questionClearly stated research question– Well-defined hypothesisWell-defined hypothesis– Two clearly-stated aims/objectivesTwo clearly-stated aims/objectives– Translational relevanceTranslational relevance– Human impactHuman impact

““Set the Stage” for your final assignmentSet the Stage” for your final assignment

Midterm AssignmentMidterm Assignment

What is NOT necessaryWhat is NOT necessary– Detailed methodologyDetailed methodology– Discussion of experimental planDiscussion of experimental plan

DO NOT make this about your DO NOT make this about your research directly!research directly!

Midterm Assignment: Midterm Assignment: Research PlanResearch Plan ““Set the Stage”Set the Stage”

– Background of your questionBackground of your question– Clinical and translational relevanceClinical and translational relevance– Rationale for your choiceRationale for your choice– What models and systems will you be What models and systems will you be

usingusing

You may outline your proposed You may outline your proposed study design, but don’t make this study design, but don’t make this the focus of your discussionthe focus of your discussion

Midterm Assignment: Midterm Assignment: Research PlanResearch Plan Why are we making you do this?Why are we making you do this?

– Experience with a different style of scientific Experience with a different style of scientific writingwriting

– Grad students, post-docs and people Grad students, post-docs and people applying for faculty positions have to write applying for faculty positions have to write these statements of research interest in these statements of research interest in applying for fellowships/positionsapplying for fellowships/positions

Write for a general audience – OK to be Write for a general audience – OK to be nontechnicalnontechnical

Good practice to solidify your ideas Good practice to solidify your ideas before launching into the more complex before launching into the more complex – and technical – grant writing exercise– and technical – grant writing exercise

Term PaperTerm Paper

““Medical Biophysics Translational Medical Biophysics Translational Research Grant” Research Grant”

Full research proposalFull research proposal– 5 pages5 pages– Single spacedSingle spaced– Not including figures, tables, references, title Not including figures, tables, references, title

pagepage

This grant is to be built around the This grant is to be built around the translational research aim you designed translational research aim you designed for the Midterm Assignmentfor the Midterm Assignment

Final Assignment: Final Assignment: Grant ProposalGrant Proposal Longer and more complex than the Longer and more complex than the

research planresearch plan– Similar to grant and fellowship Similar to grant and fellowship

proposals you will be writing as a proposals you will be writing as a graduate studentgraduate student

– Similar to the design for a Similar to the design for a reclass/qualifying exam proposalreclass/qualifying exam proposal

– Intended to give you a sense of the form Intended to give you a sense of the form and function in a scientific proposaland function in a scientific proposal

Meant to be a “window into your Meant to be a “window into your thought processes” if well writtenthought processes” if well written

Term PaperTerm Paper

ComponentsComponents– A brief introduction to the research area, including A brief introduction to the research area, including

literature review and rationale for your proposed literature review and rationale for your proposed studystudy

– A clearly stated research question, and summary of A clearly stated research question, and summary of the preliminary data for the project (this can be the preliminary data for the project (this can be derived from the literature, with the appropriate derived from the literature, with the appropriate references)references)

– A clearly stated hypothesisA clearly stated hypothesis– At least two specific aims of your research, including At least two specific aims of your research, including

at least one clear translational research aimat least one clear translational research aim– The experimental approach, availability of samples, The experimental approach, availability of samples,

methodologies, anticipated outcomes and potential methodologies, anticipated outcomes and potential pitfalls of each aim should be laid outpitfalls of each aim should be laid out

– A clear description of the translational nature of the A clear description of the translational nature of the aim should also be presentedaim should also be presented

– A statement of clinical relevance/impactA statement of clinical relevance/impact

Oral PresentationOral Presentation

Short (~10-12 minute) oral Short (~10-12 minute) oral presentation outlining your presentation outlining your research proposalresearch proposal

Focus on translational aims Focus on translational aims and impactand impact

““Interview” for grant Interview” for grant proposalproposal

Assignment NotesAssignment Notes

Late papers will not be acceptedLate papers will not be accepted

Electronic submissions are preferredElectronic submissions are preferred

Your research question CANNOT be derived from your own workYour research question CANNOT be derived from your own work– To verify this, we ask for a copy of your research abstract (e.g., your To verify this, we ask for a copy of your research abstract (e.g., your

project proposal abstract from your first committee meeting or project proposal abstract from your first committee meeting or qualifying/reclassification exam; or your student seminar abstract)qualifying/reclassification exam; or your student seminar abstract)

– Failure to abide by this rule will result in an automatic failing grade Failure to abide by this rule will result in an automatic failing grade in the course; there will be no opportunity for a make-up assignmentin the course; there will be no opportunity for a make-up assignment

– You may stay within the same disease, but you must choose a You may stay within the same disease, but you must choose a different aspect of it (for e.g., if you are working on a particular different aspect of it (for e.g., if you are working on a particular signaling pathway, you cannot do that, but you can do something signaling pathway, you cannot do that, but you can do something based on imaging modalities in the same disease, or experimental based on imaging modalities in the same disease, or experimental therapeutics, etc.)therapeutics, etc.)

– You cannot work on the same proteinYou cannot work on the same protein– You may apply a technique you’re learning or working on currently to You may apply a technique you’re learning or working on currently to

your research question, but remember that a research question isn’t your research question, but remember that a research question isn’t based around a techniquebased around a technique

– You can, also, if you like, extrapolate from your research if it is very You can, also, if you like, extrapolate from your research if it is very basic, and consider how you would apply it 5 or 10 years from now, in basic, and consider how you would apply it 5 or 10 years from now, in the clinical settingthe clinical setting

– If you have any questions, please do not hesitate to contact Dr. If you have any questions, please do not hesitate to contact Dr. Sukhai Sukhai

What is Translational What is Translational Research?Research? For the purposes of this grant, “Translational For the purposes of this grant, “Translational

Research” is defined to be use of clinically Research” is defined to be use of clinically obtained samples in at least one major aim of obtained samples in at least one major aim of the proposalthe proposal

Specifically, use of:Specifically, use of:– Human subjects (with malignancy or disease)Human subjects (with malignancy or disease)– Primary tissues/fluids (e.g., bone marrow samples Primary tissues/fluids (e.g., bone marrow samples

or tumour biopsies) derived from patients with or tumour biopsies) derived from patients with malignancy or diseasemalignancy or disease

You CANNOT use for this purpose:You CANNOT use for this purpose:– Mice or other animal modelsMice or other animal models– Cell lines derived from patientsCell lines derived from patients– Other cell culture systemsOther cell culture systems

But I Don’t Do But I Don’t Do Translational Translational Research!Research! Don’t worry! Fewer of us than you might Don’t worry! Fewer of us than you might

think do purely translational researchthink do purely translational research Objective of MBP 1018 is to develop your Objective of MBP 1018 is to develop your

ability to conceive of and integrate ability to conceive of and integrate translational concepts into your thinkingtranslational concepts into your thinking

If you do:If you do:– Basic research (with cell lines or animal Basic research (with cell lines or animal

models)models)– Structural researchStructural research– Photonics or imaging researchPhotonics or imaging research

……There are translational applications in There are translational applications in the future – just think about them!the future – just think about them!

But I Don’t Do But I Don’t Do Oncology Research!Oncology Research! That’s OK – think about the pathways you That’s OK – think about the pathways you

work on.work on.

Do they have application to cancer in Do they have application to cancer in some way?some way?

Can you draw connections outside of your Can you draw connections outside of your own immediate sphere of research?own immediate sphere of research?

If you can, write about those connections.If you can, write about those connections.

Course ScheduleCourse Schedule

DATEDATE TOPICTOPIC LECTURERLECTURER

JAN. 12JAN. 12 IntroductionIntroduction M. SukhaiM. Sukhai

JAN. 19JAN. 19 Imaged based monitoring of individual response to treatmentImaged based monitoring of individual response to treatment G. CzarnotaG. Czarnota

JAN. 26JAN. 26 The importance of genetic variation in oncologyThe importance of genetic variation in oncology G. LiuG. Liu

FEB. 02FEB. 02 Novel models and methods for assessment of new targeted agents in Novel models and methods for assessment of new targeted agents in oncology oncology

D. HedleyD. Hedley

FEB. 09FEB. 09 Lung cancer genomics and patient individualizationLung cancer genomics and patient individualization M. TsaoM. Tsao

FEB. 16FEB. 16 Image guided personalized therapyImage guided personalized therapy D. JaffrayD. Jaffray

FEB. 23FEB. 23 Cancer Immunotherapy Cancer Immunotherapy L. HguyenL. Hguyen

MAR. MAR. 0202

Novel targeted drugs and their introduction in the clinicNovel targeted drugs and their introduction in the clinic L. SiuL. Siu

MAR. MAR. 0909

Tumor microenviornment and metabolism in radiation oncologyTumor microenviornment and metabolism in radiation oncology M. MilosevicM. Milosevic

MAR. MAR. 1616

Novel risk factorsNovel risk factors N. BoydN. Boyd

MAR. MAR. 2323

Breast cancer oncogenesis and new targetsBreast cancer oncogenesis and new targets M. ReedjikM. Reedjik

MAR. MAR. 3030

Imaging in oncologyImaging in oncology G. StaniszG. Stanisz

APR. 06APR. 06 Novel targets in leukemiaNovel targets in leukemia M. MindenM. Minden

APR. 13APR. 13 Oral PresentationOral Presentation ClassClass

APR. 20APR. 20 Oral PresentationOral Presentation ClassClass

APR. 27APR. 27 Oral Presentation / Optional Tutorial SessionOral Presentation / Optional Tutorial Session ClassClass

MAY 04MAY 04 Final Assignment DueFinal Assignment Due

Tutorial 1: Analysis of Tutorial 1: Analysis of Primary PapersPrimary Papers Rules of Reading a PaperRules of Reading a Paper

Things to look forThings to look for

CRITICAL CRITICAL READINGREADING

2 Rules

Rule 1Rule 1

Read the paper

Rule 1bRule 1b

Read all of the paper

Rule 2Rule 2

Look at the data

Critical PointsCritical Points

Understand the details of the Understand the details of the researchresearch

– Initial observations/backgroundInitial observations/background– Formulate the question/problemFormulate the question/problem– Is there a hypothesis?Is there a hypothesis?– Is the methodology valid?Is the methodology valid?– Is the experiment appropriate?Is the experiment appropriate?– Are the data of high quality?Are the data of high quality?– Are the appropriate controls present?Are the appropriate controls present?– Are the data consistent with other data?Are the data consistent with other data?

Discussion PointsDiscussion Points

Understand the details of the Understand the details of the researchresearch

– Initial observations/backgroundInitial observations/background– Formulate the question/problemFormulate the question/problem– Is there a hypothesis?Is there a hypothesis?– Is the methodology valid?Is the methodology valid?– Is the experiment appropriate?Is the experiment appropriate?– Are the data of high quality?Are the data of high quality?– Are the appropriate controls present?Are the appropriate controls present?– Are the data consistent with other data?Are the data consistent with other data?

Things to look forThings to look for

Was the methodology appropriate for Was the methodology appropriate for the question being asked?the question being asked?

Were the data consistent with the Were the data consistent with the methodology?methodology?

Were the data internally consistent?Were the data internally consistent? Do the data make sense?Do the data make sense? Were the controls appropriate?Were the controls appropriate? Can you conclude what the authors Can you conclude what the authors

concluded from their data?concluded from their data? Do you agree/disagree with the authors’ Do you agree/disagree with the authors’

interpretation?interpretation? Do you agree with the “big picture” the Do you agree with the “big picture” the

authors present?authors present?

““The Matrix”The Matrix”

GOOD WRITINGGOOD WRITING

GOOD SCIENCEGOOD SCIENCE

GOOD WRITINGGOOD WRITING

BAD SCIENCEBAD SCIENCE

BAD WRITINGBAD WRITING

GOOD SCIENCEGOOD SCIENCE

BAD WRITINGBAD WRITING

BAD SCIENCEBAD SCIENCE

HypothesesHypotheses

HypothesesHypotheses

Are supposed to be falsifiableAre supposed to be falsifiable Can be specificCan be specific It’s OK if they end up being It’s OK if they end up being

WRONG!WRONG!

Hypotheses MUST agree with Hypotheses MUST agree with the objectives under the objectives under investigationinvestigation

A Bad HypothesisA Bad Hypothesis

Objective:Objective:– To determine the association between To determine the association between

Gene X and patient outcome in AMLGene X and patient outcome in AML

Hypothesis:Hypothesis:– Gene X is associated with AMLGene X is associated with AML– Gene X is involved in the DNA damage Gene X is involved in the DNA damage

responseresponse– AML patients that demonstrate AML patients that demonstrate

impaired DNA damage have a poor impaired DNA damage have a poor prognosisprognosis

A Good HypothesisA Good Hypothesis

Objective:Objective:– To determine the association To determine the association

between Gene X and patient between Gene X and patient outcome in AMLoutcome in AML

Hypothesis:Hypothesis:– Expression of Gene X is associated Expression of Gene X is associated

with poor prognosis in AMLwith poor prognosis in AML

Optional Writing Optional Writing TutorialsTutorials

……Will arrange if enough Will arrange if enough students are interestedstudents are interested

Questions?Questions?