Keys of excellence in research

Prof. Mohamed L. Salem Director, Grants, Innovation & Technology Transfer Center (GITTC)

Director, Center of Excellence in Cancer Research (CECR)

Tanta University

Faculty of Dentistry, Tanta University May 30, 2015

Keys of excellence in research Tanta university as a success story

Microbe Immune

Interaction

Cancer Immune

Interaction

HCV Immune

Interaction

Cancer Biology

CTC/CSC

1894 -1990 1992 – 1995

1995-1997 2010-2014

2001-2010

1 2 1997 - 2001

4 3

5

6

FACULTY OF SCIENCE TANTA UNIVERSITY, EGYPT

Medical Institute of Bioregulation Kyushu University, Japan

Medical University of South Carolina (MUSC) CHARLESTON, SC USA

Cancer Immunotherapy

CD8+ T cells are

specific to the MHC-1

gp10025-33 melanoma

peptide

Donor

Tg

Pmel Culture T cells and stimulate with +

gp10025-33 peptide ± IL12 for 3~5 days

CD44

CD

62

L

Pept + IL12

(pmelIL12 ) Pept alone

(pmelsham )

Our anti-tumor T cell adoptive

transfer model

PBS

CTX

PBS

CTX

Vaccination

+ Poly (I:C)

Phases post CTX treatment relative to adoptive T cell

therapy (Salem, CII 2010)

•Creation of a space niche due to

the induced lymphopenia

•Homeostatic expansion of T cells

•Elimination of regulatory cells

•Elimination of cytokine competition

•Microbial translocation

•Activation of dendritic cells

• Cellular recovery from lymphopenia

• Less of lymphopenia

• Less homeostatic proliferation of T cells

• Expansion of immature dendritic cells

3 6 9 12 15 18

Days after CTX treatment

Nu

mb

er

of

de

nd

riti

c c

ell

s

Lymphopenic phase Recovery phase

0 -1

ACT Antigen priming

+ TLR agonists Antigen boosting

+ TLR agonists

20

DCs

Donor

T cells

CTX

Pmel 12

CTRL

Regression of metastatic melanoma after adoptive

transfer of in vitro activated T cells

Peptide

Mature DCs Monocytes

Monocytes GM-CSF

IL-4

Immature DCs

Tumor

lysate

Viral

vector

MHC class-I

Peptide

complex Inject dendritic cells

Tumor

CTL

Clinical Trial: Pancreatic Cancer Patients

TAG of WAR

Types of Regulatory Cells

Regulatory T cells

Treg cells

MDSC

Immunity

Does cyclophosphamide-containing

chemotherapy increase levels of circulating

MDSCs in breast cancer patients?

ddAC (doxorubicin and cyclophosphamide) every 2 weeks (60/600 mg/m2)

ddT (Paclitaxel every 2 weeks (175 mg/m2))

Pegfilgrastim 6mg SQ

ddAC ddT

R1

R1

Gated on R1

Lin

HLADR

CD

33

CD11b

Normal volunteer

Stage IV breast cancer

ddAC Chemotherapy

1.19%

22.3%

19.6%

R1

Phenotype of MDSC by Whole Blood

Flow Cytometry

Diaz-Montero, et al.

Cancer Immunol Immunother. 2008

MD

SC

(%

)

BL ddAC ddT

12

.55

10

25

MD

SC

/μL

BL ddAC ddT

10

02

50

50

01

00

02

50

0

Increased MDSC levels during ddAC but not

during ddT therapy

n=17



Cell proliferation

IL-2

IFN-

0

2

4

6

8

10

N N P10 P59 P26 P26

BL ddAC

x1

05

ce

lls

22%26%

24%

0.3% 0.55%

3.83%

0

5000

10000

15000

20000

25000

pg

/ml

0

20000

40000

60000

80000

100000

120000

pg

/ml

Decreased T cell responses in cancer patients

correlate with increased levels of MDSCs



Capacity Building

Research Elements

Experience

Expertise

Infrastructure

Skills

Knowledge

Research Needs

Communication

Lab Space

Budget

Manpower

Leadership

Project-based Research

Science

Patents

Publications

Competitiveness Internationalization

Marketing

Levels of Research Capacity Building

Five key elements of an organization’s design

The Star Model

Components of

Research Capacity Development

FACTORS INFLUENCING RESEARCH PRODUCTIVITY (Individual Factors)

• In-depth knowledge of the research area

• Basic research skills

• Socialization

• Advisory/Mentor functioning

• Work habits

• Professional network

• Productive local peer support

• Simultaneous projects

• Sufficient work time and Commitment

• Supportive environment

Personal motivation

FACTORS INFLUENCING RESEARCH PRODUCTIVITY (Institutional Factors)

Phases of Research Capacity Development

Tanta University

Grants, Innovation & Technology Transfer Center (GITTC)

• Technology Transfer Office (TTO)

• Grants and International Cooperation Office (GICO)

• Technology Innovation Support Center (TISC)

Projects per domain submitted to Tanta University Research fund (2011-2013)

Total: 101

Material Sciences 17%

Biotechnology 16%

Water 12%

Integrated Projects

12%

Project No, Hepatitis, 11%

Stem cells 11%

Education & Socialization

8%

Agricultural residues

7%

Renewable Energy 6%

Projects submitted per faculty to Tanta University Research Fund (2011-2013)

0

5

10

15

20

25

30

35

40

45 42

19

16

10

5 3 2 2 1 1 0 0 0

National and International funded projects

(2010-2014)

•> 42 million LE

• Tanta University Central Lab (5m LE; STDF) • Tanta University CECR (10m LE; STDF) • Faculty of Medicine, DTPC (5m LE; STDF) • Faculty of Medicine (2m; 2 projects; STDF) • Faculty of Science (4 projects; 6m; STDF) • Faculty of Agriculture (1 project; Mobility, FP7) • Faculty of Engineering (3 projects, 5m; STDF) • Ministry of Int Cooperation (about 1m) • Academy of Scientific Research & Technology • Ministry of Higher Education (about 10m) Medicine, Engineering, Science, Education

National and International Grants

انجازات الجامعة في الحصول

تنافسيةمشروعات علي

(2010 -2014)

جنيه مليون 40

Center of Excellence in Cancer Research (CECR)

الفريق أثناء توقيع العقد

Overall Aim of The Proposal

1. Establish "Center of Excellence in Cancer Research (CECR)” and furnish the center with three state-of-art equipment, including: – Flow Cytometr

– Next generation microarray platform

– FLEXMAP 3D advanced liquid based multiplexing system which bridging the proteome and the genome.

– Isoflux

2. Perform cutting-edge preclinical and clinical cancer research

Correlate clinical performance with genomic and proteomic profiling of primary tumors with circulating tumor cells (CTCs) and cancer stem cells (CSCs).

Use CTCs and CSCs to genotype for mutated genes as pharmacodynamic data for molecularly targeted drugs.

Wider Objectives of The Proposal

مركز تكنولوجيا البصمة الجينية كأداة لتطوير انشاء األبحاث التطبيقية المتقدمة لتشخيص السرطان

Genetic Signature center for fostering next generation translational

كلية الطب جامعة طنطا

microRNAs: tools for cancer

diagnosis

Affymetrix genechip microarray

FLEXMAP 3D™ Proteomic System

BD FacsCanto Flow Cytometer

The IsoFlux System delivers

a highly enriched CTC

sample ready for analysis

MiSeq – NGS

52.3 cm

Multidisciplinary team work can build success with

sustainability

To Be • United

• Patient

• Optimistic

• Enthusiastic

• Open minded

• Overcome the obstacles

• Look for new partners

In

Out

Thank you

Thank you

Keys of excellence in research

Science

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