Researching with the Big Guys: Community Colleges and Cancer Research

Dr. Firouz DarroudiNelson RodriguesDr. 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 Microscopy3D Image of Breast Cancer Cell from SEM 3D Image of Lung Cancer Cells from SEM

Cancer Research InfrastructureGerman 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

Cell death (Apoptosis, necrosis)

Cell cycle arrest

G1S

G2M

DNA Repair Complete

Incomplete

*Genomic instability

*Mutations

*Chromosomal aberrations

Cancer and Genetic

Diseases

Damaged

DNA• G1/S checkpoint

(ATM, ATR, p53)

• S-phase checkpoint(ATM, p53, Chk2)

• G2/M checkpoint(Cdc2 / CyclinB)

DSB

SS

B

BD

SSB = Single Strand Breaks

DSB = Double Strand breaks

BD = Base Damage

Biological Cytogenetic Assays for Assessing genotoxic potential of Biological Cytogenetic Assays for Assessing genotoxic potential of physical and chemical agents in mammalian cellsphysical and chemical agents in mammalian cells

1.1. DicentricsDicentrics

(in metaphases)(in metaphases)

2. Micronuclei 2. Micronuclei (in binucleated cells)(in binucleated cells)

3. Premature Chromosome Condensation (PCC) 3. Premature Chromosome Condensation (PCC) (in interphases)(in interphases)

4. Translocations using Fluorescence 4. Translocations using Fluorescence in situin situ hybridization (FISH) hybridization (FISH) (in metaphases)(in metaphases) Darroudi et al., International Atomic Energy Agency (IAEA), Technical Reports Series No. 405, 2001, 2011.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, 2002Darorudi et al., Medical Preparedness and Response, Educational Materials IAEA and WHO, 2002

I.A.E.A. Manuals (I.A.E.A. Manuals (Darroudi and co-workersDarroudi and co-workers) on Cytogenetic Assays for ) on Cytogenetic Assays for Detecting Chromosomal Alteration immediately and retrospectivelyDetecting Chromosomal Alteration immediately and retrospectively

Clinical Trials(Cell killing, Cancer)

Cellulare Damages (DNA, Protein, Membrane, Cellular organization )

Difference in sensitivity

Genetic Differences

Future Plans:

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

Low and high dose Radiationand Chemicals

CancerDNA damage

DNA Human

Cell Tissue / organ

Smoking (25-40%)

Nutrition (10-70%)

Alcohol (2-4%)

Occupation (2-8%)

Mycotoxins (4%)

Geophysical Faktors (2-4%)Infections (2-4%)

Environmental pollution (1-5%)Sunlight / skin (2%)

Medicinal causes (2-4%)Nitrosamines / stomach (3%)

Estimated Cancer Mortality (USA)(after Doll and Peto 1981 and Marquardt 1994, 2004)

1

2

CASE-MultiCASE

Elucidating the genotoxic, anti-genotoxic and anti-cancer activity of plants, spices and dietary componeents in Qatar

Future Plans: Application of State of the art molecular biology assays

1 DSB

One -H2AX focus

Human

lymphocyte

Antibody anti phosphoserine-H2AX

-H2AX : Applications-H2AX : Applications

Environmental studies

Clinical Trials Patients Care

Redon et al., 2010Basic research on DNA repair

Darroudi et al., 2007 (Mut. Res.); Redon et al., 2010

Redon et al., 2009;

Vrouwe…Darroudi, 2007 (HMG)

Van Lelij…Darroudi et al., 2009 (Plos One)

Aging

Nakamuraet al., 2004

Drug Development

Bonner et al., 2008

Tumorigenesis

Sedelnikovaet al., 2004

DSBDSB

-H2AX

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

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.