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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
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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 • Detecting causes of cancer • Detecting biomarkers for cancer of different origins • 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 DNA M Cell cycle arrest G2 • G1/S checkpoint(ATM, ATR, p53) • S-phase checkpoint(ATM, p53, Chk2) • G2/M checkpoint(Cdc2 / CyclinB) S DSB G1 SS B DNA Repair Complete *Genomic instability*Mutations *Chromosomal aberrations BD Cancer and GeneticDiseases Incomplete SSB = Single Strand Breaks DSB = Double Strand breaks BD = Base Damage Cell death (Apoptosis, necrosis)
Biological Cytogenetic Assays for Assessing genotoxic potential of physical and chemical agents in mammalian cells • 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 ) Difference in sensitivity Clinical Trials (Cell killing, Cancer)
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 Future Plans: DNA damage Cancer Low and high dose Radiation and Chemicals DNA Human Cell 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
One -H2AX focus 1 DSB Human lymphocyte Future Plans: Application of State of the art molecular biology assays Antibody anti phosphoserine-H2AX
DSB Aging -H2AX Redon et al., 2009; Vrouwe…Darroudi, 2007 (HMG) Van Lelij…Darroudi et al., 2009 (Plos One) Nakamura et al., 2004 Tumorigenesis Clinical Trials Patients Care Environmental studies Basic research on DNA repair Drug Development Redon et al., 2010 Sedelnikova et al., 2004 Bonner et al., 2008 Darroudi et al., 2007 (Mut. Res.); Redon et al., 2010 -H2AX : Applications Radiation Research
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 • Discovering New Biomarker(s) for Cancer • Improving Therapy Regimen for Cancer Patients • Discovering Origin of Cancer • Discovering New Drugs against Cancer
A search for detecting anticancer drugs against: Breast, Ovarian and Melanoma Cancer Calomeria amoranthoides
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)