ramy karam aziz, phd - national academies · rizkallah et al. cppm 2012 . ... tamer essam, fopcu...

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Ramy Karam Aziz, PhD Chair, Microbiology and Immunology, Faculty of Pharmacy, Cairo University

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Page 1: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

Ramy Karam Aziz, PhD Chair, Microbiology and Immunology, Faculty of Pharmacy, Cairo University

Page 2: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Mariam Rizkallah Rama Saad

AbdelRahman Aly

Mariam Lotfy Sara Zahran

Marina Ghattas Moamen El-Massry Amal Hamdy

Page 3: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

Prelude

Page 4: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

¡  NIH definition of precision medicine*:

"an emerging approach for disease treatment and prevention that takes into account individual variability in §  genes,

§  environment,

§  lifestyle

for each person.”

*https://ghr.nlm.nih.gov/primer/precisionmedicine/definition

5 Nov 2018 Arab American Frontiers 2018

Page 5: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Page 6: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Page 7: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

How it all started?

Page 8: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Page 9: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

~1013 ~1014

The Economist. Aug 2012

Page 10: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Page 11: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

Microbiome cloud model... ¡  Variations:

§  Inter-individual §  Intra-individual ▪  Spatial ▪  Temporal ▪  Developmental ▪  Hormonal ▪  Geographical

5 Nov 2018 Arab American Frontiers 2018 ElRakaiby et al. OJIB 2014

Page 12: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

¡  We are inhabited by a cloud of genomes and the genes they carry, mostly coming from microbes and viruses that we have been “domesticating” for long long time.

¡  This cloud enriches our gene pool, which, unlike ours, is wrapped in uncertainty. That’s why the microbiome is exciting!

5 Nov 2018 Arab American Frontiers 2018

Page 13: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,
Page 14: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

Ø The interaction between a host and its associated microbiota mostly plays a beneficial role in the host’s health.

Ø The microbiota has a valuable role during normal homeostasis, modifying the host's immune system and prompting host development and physiology.

Ø Any disruption of this homeostatic coexistence leads to dysbiosis, which has been powerfully associated with human disease.

Source: Pflughoeft, K.J. and J. Versalovic. Annu. Rev. Pathol. Mech. Dis. 2012. 7:99–122

5 Nov 2018 Arab American Frontiers 2018

Page 15: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Page 16: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

¡  Conjunctivitis signature?

¡  Intra- vs. Inter-individual variation

5 Nov 2018 Arab American Frontiers 2018 Analysis: Moamen elMasry

Page 17: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

¡  Nasal microbiota competition with Staphylococcus aureus

5 Nov 2018 Arab American Frontiers 2018

Page 18: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Page 19: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Aly et al. Gut Pathogens 2016

PC3 (9.72%)

PC2 (10.28 %)

PC1 (55.68%)

Page 20: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Aly et al. Gut Pathogens 2016

Page 21: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

1. Microbiome = clouds of microbes and their genomes with different levels of variability.

2. Microbes play major functions that affect health, disease, and nutrition.

3. Reciprocally, food, natural products, and prebiotics play a pivotal role in disrupting or restoring microbial balance.

How about the effect of these resident microbes on pharmacotherapy (drugs)?

5 Nov 2018 Arab American Frontiers 2018

Page 22: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

PharmacoMicrobiomics

Page 23: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Page 24: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

The microbiome cloud model

5 Nov 2018 Arab American Frontiers 2018 ElRakaiby et al. OJIB 2014

Page 25: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Page 26: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Page 27: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Digoxin

Acetaminophen

EROD + GSTA –

Saad et al. Gut Pathogens 2013

Page 28: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

ElRakaiby et al. OJIB 2014

Page 29: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

http://pharmacomicrobiomics.org

Rizkallah et al. CPPM 2012

Page 30: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

http://pharmacomicrobiomics.org

Rizkallah et al. CPPM 2012

Page 31: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Page 32: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018 Hamdy et al. OMICS 2018

Page 33: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

PharmacoMicrobiomics

Page 34: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

IN VITRO/ IN VIVO

¡  Pharmacomicrobiomics of Voriconazole in cancer patients

¡  Azodye degraders from skin and gut

¡  How bacterial pathogens react to sugars of the gut environment (rhamnose, fucose, etc.)

¡  Microbiota and differential effects on food and food additives à cancer?

IN SILICO

¡  Azoreducatases and dye peroxidase mining tools

¡  Beta glucuronidase data mining tools

5 Nov 2018 Arab American Frontiers 2018

Page 35: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

IN VITRO/ IN VIVO

¡  Pharmacomicrobiomics of Voriconazole in cancer patients

¡  Azodye degraders from skin and gut

¡  How bacterial pathogens react to sugars of the gut environment (rhamnose, fucose, etc.)

¡  Microbiota and differential effects on food and food additives à cancer?

IN SILICO

¡  Azo-reducatases and dye peroxidase mining tools

¡  Beta glucuronidase data mining tools

5 Nov 2018 Arab American Frontiers 2018

Page 36: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

5 Nov 2018 Arab American Frontiers 2018

Page 37: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

¡  Our cells are surrounded by a microbiome cloud that interacts with us and affects our health, disease, nutrition, and therapy.

¡  Decoding this microbiome cloud is not straightforward; some sequences remain challenging (phages, mobile elements, etc.).

¡  The future of “our” biology is eternally connected to those intimate strangers.

We have a common destiny! 5 Nov 2018 Arab American Frontiers 2018

Page 38: Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU Bas Dutilh, Utrecht Pep Charusanti, UCSD Rania Siam, AUC Mya Breitbart, USF Rob Edwards,

Marwa ElRakaiby Soha Gamal-Eldin

And Tamer Essam, FOPCU

Bas Dutilh, Utrecht Pep Charusanti, UCSD

Rania Siam, AUC Mya Breitbart, USF

Rob Edwards, SDSU Alex Mira, FISABIO Jack Gilbert, ANL

Jarrad Marcel, ANL Janet Johnson, PNNL

5 Nov 2018 Arab American Frontiers 2018

Rick Stevens Argonne National Laboratory

Bernhard Palsson UC San Diego

Mariam Rizkallah Rama Saad

Ross Overbeek The Fellowship for

Interpretation of Genomes