Transcript Long and Darroudi Presentation - Global Innovators Conference 2013

Researching with the Big
Guys: Community
Colleges and Cancer
Research
Dr. Firouz Darroudi
Nelson Rodrigues
Dr. Michael Long
April 5, 2013
Presentation Overview
• The Cost of Cancer Research
• Community College Cancer Research Activity
• CNAQ Cancer Research – Origins and
Development
• Training Students for Cancer Research
• Future Plans
The Cost of Cancer Research
• Cancer research is expensive
– Personnel (scientists, oncologist, radiologists
– Equipment (microscopy, MRIs, shipment costs!)
– Infrastructure (research complexes, compliance)
– Drug development and patenting
Cancer Microscopy
3D Image of Breast Cancer Cell from SEM
3D Image of Lung Cancer Cells from SEM
Cancer Research Infrastructure
German Cancer Research Centre
M.D. Anderson Cancer Center
Cancer Drug Development
• Average cost of R&D to bring one cancer drug
to market: $802 million
• Risk!!!
– Only 1 in 1000 new compounds make it to human
trials testing
– Of those, only 1 in 5 receive FDA approval
Community College Cancer Research Activity
• St. Vincent and the Grenadines Community College
(Caribbean)
• Aroka Ramsey Community College (Minnesota)
• Capital Community College (Connecticut)
Community College Cancer Research Activity
• Other Cancer Research Activity at CCs
– Pain studies
– Ethnographic studies
– KAP studies
– Lifestyle research
– Nutrition studies
Community College Cancer Research Activity
• Other Initiatives
– CIHR Community College Innovation Program
(Canada)
– Community College Undergraduate Research
Initiative (CCURI) www.ccuri.org (US)
– NIH’s Community College Summer Enrichment
Program (US)
– QNRF (UREP Program) in Qatar
CNAQ Cancer Research – Origins and
Development
•
Research Environment in Qatar is unique. National Priorities tied to research
in order to diversify from a carbon economy.
– well resourced financially (2.8% GDP)
– QNRF
– But …
• Little data
• Few grads, post docs
• Lab spaces, equipment, technicians in early stages
• Top-down research model vs lateral or bottom-up
CNAQ Resources
• Support – Executive, Deans, Lab Managers,
Facilities, Procurement
• Faculty and Students - enthusiastic
• Equipment
CNAQ Equipment
Zeiss Axio A1 Imager Flourescence Microscope
Centrifuge and Waterbath
CNAQ Equipment
-70 Freezer
Polymerase Chain Reaction (PCR)
CNAQ Equipment
Microscopes/Lab Bench
Sample Preparation Fume Hood
Professor Firouz Darroudi
• Radiation Protection Training (IAEA) for MRTs
• Research lectures
• Recognized potential of CNAQ Resources:
Faculty, Students, Equipment
• Fertile research ground in Qatar
Professor Firouz Darroudi
• Experience with developing international labs
• Research Consultant
• Workshops
–
–
–
–
Cytogenetic Short Term Assays in Genetic Toxicology
Genetic Counseling
Radiation Mutagenesis & Protection
Human Risk Assessment & Population Monitoring
Training Students for Cancer Research
1. Detecting causes of cancer
2. Detecting biomarkers for cancer of different
origins
3. Improving cancer therapy regimen
Training Students for Cancer Research
Training is mainly implemented by organizing
different workshops on cellular and molecular
biology assays in order to explore the effect of
physical and chemical agents on human DNA by
analysing chromosomal alterations. WHY?
1. DNA in the nucleus is organized via chromosomes
2. Chromosomal aberrations were found to be
the biomarker for cancer in unexposed cohorts
Responses of the cell upon induction of DNA damage
Damaged
M
G2
Cell cycle arrest
DNA
• G1/S checkpoint
(ATM, ATR, p53)
S
DS
B
G1
• S-phase checkpoint
(ATM, p53, Chk2)
• G2/M checkpoint
S
S
DNA Repair
Complete
(Cdc2 / CyclinB)
B
B
D
*Genomic instability
Incomplete
*Mutations
*Chromosomal aberrations
SSB = Single Strand Breaks
DSB = Double Strand breaks
BD = Base Damage
Cell death (Apoptosis, necrosis)
Cancer
and Genetic
Diseases
Biological Cytogenetic Assays for Assessing genotoxic potential of
physical and chemical agents in mammalian cells
1. Dicentrics
(in metaphases)
2. Micronuclei (in binucleated cells)
3. Premature Chromosome Condensation (PCC) (in interphases)
4. Translocations using Fluorescence in situ hybridization (FISH)
(in metaphases)
Darroudi et al., International Atomic Energy Agency (IAEA), Technical Reports Series No. 405, 2001, 2011.
Darorudi et al., Medical Preparedness and Response, Educational Materials IAEA and WHO, 2002
I.A.E.A. Manuals (Darroudi and co-workers) on Cytogenetic Assays for
Detecting Chromosomal Alteration immediately and retrospectively
Future Plans:
Genetic
Differences
Cellulare Damages
(DNA, Protein, Membrane, Cellular organization )
Clinical Trials
(Cell killing, Cancer)
Difference in
sensitivity
Future Plans:
DEPARTMENT OF Radiation Genetics and Chemical
Mutagenesis at CNA-Q:
A multi–disciplinary approach
DNA DAMAGE RESPONSES AND REPAIR, GENOMIC
INSTABILITY CHEMICAL AND RADIATION INDUCED CANCER
DNA
damage
DNA
Cell
Cancer
Low and high dose Radiation
and Chemicals
Human
Tissue / organ
Estimated Cancer Mortality (USA)
(after Doll and Peto 1981 and Marquardt 1994, 2004)
Smoking (25-40%)
Nutrition (10-70%)
Occupation (2-8%)
Mycotoxins (4%)
Alcohol (2-4%)
Geophysical Faktors (2-4%)
Infections (2-4%)
Medicinal causes (2-4%)
Nitrosamines / stomach (3%)
Sunlight / skin (2%)
Environmental pollution (1-5%)
Elucidating the genotoxic, anti-genotoxic and anti-cancer activity of
plants, spices and dietary componeents in Qatar
CASE-MultiCASE
1
2
Future Plans: Application of State of the art molecular biology assays
One -H2AX focus
Human
lymphocyte
1 DSB
Antibody anti phosphoserine-H2AX
-H2AX : Applications
DSB
Aging
Radiation
Research
-H2AX
Redon et al., 2009;
Nakamura
et al., 2004
Vrouwe…Darroudi, 2007 (HMG)
Van Lelij…Darroudi et al., 2009 (Plos One)
Tumorigenesis
Sedelnikova
et al., 2004
Environmental
studies
Clinical Trials
Patients Care
Basic research on Drug Development Redon et al., 2010
DNA repair
Bonner et al., 2008
Darroudi et al., 2007 (Mut.
Res.); Redon et al., 2010
Application of COBRA-MFISH for detecting structural
and numerical aberrations (Biomarkers for cancer)
•
A normal metaphase (XX)
X-irradiated human peripheral blood
lymphocytes
Szuhai & Tanke, Nature Protoc. 1, 264-275, 2006;
Darroudi et al., Radiation Protection Dosimetry 99, 189-192, 2002;
Bezrookove ..Darroudi., Genes, Chromosomes & Cancer 38, 177-186, 2003;
Darroudi et al; Cancer Letters 287, 67-74, 2010
Darroudi et al., IJRB, 2013.
f”=fragment; RT=Reciprocal Translocation; Dic=Dicentric;
bf”=bicoloured fragment
To speed up the processes of analyses by applying, Metasystem
autmatic analyser for: Automatic analysis of Micronclei in
binucleated cells, Spot counting, Metaphase finder, Comet
New Prospectives For Detecting and Treating
Cancer of Different Origins
1.Discovering New
Biomarker(s) for Cancer
2. Improving Therapy
Regimen for Cancer Patients
3.Discovering Origin of
Cancer
4.Discovering New Drugs
against Cancer
A search for detecting anticancer drugs against: Breast, Ovarian
and Melanoma Cancer
Calomeria amoranthoides
A Potent and Unique Anti-Cancer Drug
Cytogenetic assays as tools to elucidate human genome:
To detect biomarkers for cancer
To improve cancer therapy regimen (by studying local
national plant resources in Qatar)
Thank you for your attention.