Researching with the Big Guys: Community Colleges and Cancer Research
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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


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.


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