Introduction of Department of Molecular Biology for Public Health

in SCDC

Ye Lu

Shanghai Municipal Center for Disease Control & Prevention

Shanghai Institute of Prevention Medicine

April,2008

Laboratory Building

Department of Molecular Biology For Public Health (DMB)

GenomicResearch

Bio-bank

ProteomicResearch

Bio-informatics

Construction of DMB

• Bio-bank: collection, analysis and management of bio-samples

• Genomic research: SNP analysis of chronic diseases

• Proteomic research: differential proteomic research of infectious diseases and carcinoma

• Bio-informatics: research data analysis

Main Tasks of DMB

• Provide technical platform

• Cooperate on research projects

Research Projects

• Proteomic Research of Lung Cancer• Proteomic Research of Liver fibrosis• Proteomic Research of MDR-TB• SNP analysis of COPD • Early diagnosis of Breast Cancer• Hypertension, Shock & Other Cardiovascular

Diseases in Senior population

Objective

• Find serum biomarkers for early diagnosis of lung cancer.

• Explain the mechanism of the biomarkers, together with the relationship of smoking.

Proteomic Research of Lung Cancer

Population

HealthyPatients

with shadowin lung

Patientswith nubin lung

Patientswith lungcancer

Technology: SELDI-TOF-MS

Methods

• Analyze the proteomic difference between healthy serum and lung cancer patient serum.

• Screen the difference among patients with shadow/nub in lung for early diagnosis of lung cancer.

• Analyze the relationship of the difference and the exposure to smoking.

4000 5000 6000 7000 8000

4000 5000 6000 7000 8000

S5

C33

S28

C48

S50

C29

S53

C32

Progression from HBV infection to cancer

Exposureto HBV

No infection

Chronic infection

CirrhosisAsymptomaticcarriers

SlowlyProgressive

HCC

?% ?%

10%

Years

Infection

Acute infection(HBV clearance)

90%

Death

~25%

Proteomic Research of Liver fibrosis

Liver fibrosis is the middle stage in the course of

chronic HBV infection.

Objective

• Find plasma biomarkers for early diagnosis of liver fibrosis

• Explain the mechanism of liver fibrosis

Population

• For screening: patients with different stages of liver fibrosis ,but the same grade of liver inflammation

• For validation: patients with different stages of liver fibrosis and different grades of liver inflammation

Four stages of fibrosis(A～ B:S1 ～ S4)

Four grades of inflammation(A～ B:G1 ～ G4)

Grade of

Inflammation

Stage of

fibrosis G1 G2 G3 G4

S1 G1S1 G2S1 G3S1 G4S1

S2 G1S2 G2S2 G3S2 G4S2

S3 G1S3 G2S3 G3S3 G4S3

S4 G1S4 G2S4 G3S4 G4S4

Screening Population

Validation Population

Technology: 2D-DIGE

Methods

• Analyze the proteomic difference among various stages of liver fibrosis patients.

• Validate the difference in a large scale of clinical samples.

• Combine the proteomic difference with other 17 clinical tests for early diagnosis of liver fibrosis.

7 8

12

12 3 45 6

9 10

11

13 1415

16 17 18 19

20 21 22 23

24

2527

2930

2628

7 8

12

12 3 45 6

9 10

11

13 1415

16 17 18 19

20 21 22 23

24

7 8

12

12 3 45 6

9 10

11

13 1415

16 17 18 19

20 21 22 23

7 8

12

12 3 45 6

9 10

11

13 1415

16 17 18 19

7 8

12

12 3 45 6

9 10

11

7 8

12

12 3 45 6

9 10

7 8

12

12 3 45 6

7 8

12

12 3 47 8

12

7 87 8

12

12 3 45 6

9 10

11

13 1415

16 17 18 19

20 21 22 23

24

2527

2930

2628

Proteomic Research of MDR-TB

Objective

• Find new antibody against MDR-TB in the serum of TB patients.

• Identify the corresponding antigen in TB strain.

• Find new method for early diagnosis of MDR-TB.

Protein fractions

Dot blot 1-D western

SERPA

SDS-PAGE and electrotransfer to PVDFH+R

sensitiveH+R

resistent

Primary antibody sourceAutologousserum

Pool 10 sentivity sera

H+R sentivity & AutologousH+R sentivity & Pool sentivityH+R resistent & AutologousH+R resistent & Pool sentivity

｛Compare by computer

Proteins recative with autologous serum only

Recative against H+R resistent line only

Identification of antigen by mass spectrometry

ELISA analysis of clinical samples

Protein fractions

Dot blot 1-D western

SERPA

SDS-PAGE and electrotransfer to PVDFH+R

sensitiveH+R

resistent

Primary antibody sourceAutologousserum

Pool 10 sentivity sera

H+R sentivity & AutologousH+R sentivity & Pool sentivityH+R resistent & AutologousH+R resistent & Pool sentivity

｛Compare by computer

Proteins recative with autologous serum only

Recative against H+R resistent line only

Identification of antigen by mass spectrometry

ELISA analysis of clinical samples

Technology: 2D-LC based SERPA

SNP analysis of COPD patients

Air-pollution is one of the main

causes of COPD.

MolecularMechanism

SNP of related enzyme?

Working Hypothesis

Air-pollution

DNA damage

COPD

DNA repair system×

• Collect clinical samples and healthy volunteers from Tai Yuan, San Xi Province, China.

• Analyze the SNP of DNA repair enzyme genes(ERCC2/XPD, XPA and XPG).

• Analyze the relationship among environmental exposure, occupation experience, gene SNP and clinical symptom of COPD.

Breast Cancer• Have 8,000 women a

mammogram test and an epidemiology survey.

• Follow up the incidence of breast cancer among the population.

TO Evaluate the effect of

mammogram on the early diagnosis of breast cancer.

Analysis the risk facts of breast cancer.

A mammogram is an x-ray of the breast,which may find tumors that are too small to feel.

Hypertension, Stroke & Other Cardiovascular Diseases

• Have 150,000 senior a medical check-up.

• Keep the results of the examination, and do an epidemiology survey.

• Collect bio-samples of plasma, serum and whole blood.

• Follow the incidence of various diseases among the population.

Get general health information Give advice on healthcareTO

Bio-bank

We are mostly interesting in

• Criteria of sample selection

• SOP for sample collection & storage

• Maintenance & management of bio-bank

Data analysis

• Associating

• Classifying

• Modeling & Simulating

• Predicting & Testing

Thank you!