Ramy Karam Aziz, PhD - National Academies · Rizkallah et al. CPPM 2012 . ... Tamer Essam, FOPCU...

Post on 15-Jul-2020

2 views 0 download

transcript

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

5 Nov 2018 Arab American Frontiers 2018

Mariam Rizkallah Rama Saad

AbdelRahman Aly

Mariam Lotfy Sara Zahran

Marina Ghattas Moamen El-Massry Amal Hamdy

Prelude

¡  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

5 Nov 2018 Arab American Frontiers 2018

5 Nov 2018 Arab American Frontiers 2018

How it all started?

5 Nov 2018 Arab American Frontiers 2018

5 Nov 2018 Arab American Frontiers 2018

~1013 ~1014

The Economist. Aug 2012

5 Nov 2018 Arab American Frontiers 2018

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

¡  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

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

5 Nov 2018 Arab American Frontiers 2018

¡  Conjunctivitis signature?

¡  Intra- vs. Inter-individual variation

5 Nov 2018 Arab American Frontiers 2018 Analysis: Moamen elMasry

¡  Nasal microbiota competition with Staphylococcus aureus

5 Nov 2018 Arab American Frontiers 2018

5 Nov 2018 Arab American Frontiers 2018

5 Nov 2018 Arab American Frontiers 2018

Aly et al. Gut Pathogens 2016

PC3 (9.72%)

PC2 (10.28 %)

PC1 (55.68%)

5 Nov 2018 Arab American Frontiers 2018

Aly et al. Gut Pathogens 2016

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

PharmacoMicrobiomics

5 Nov 2018 Arab American Frontiers 2018

The microbiome cloud model

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

5 Nov 2018 Arab American Frontiers 2018

5 Nov 2018 Arab American Frontiers 2018

5 Nov 2018 Arab American Frontiers 2018

Digoxin

Acetaminophen

EROD + GSTA –

Saad et al. Gut Pathogens 2013

5 Nov 2018 Arab American Frontiers 2018

ElRakaiby et al. OJIB 2014

5 Nov 2018 Arab American Frontiers 2018

http://pharmacomicrobiomics.org

Rizkallah et al. CPPM 2012

5 Nov 2018 Arab American Frontiers 2018

http://pharmacomicrobiomics.org

Rizkallah et al. CPPM 2012

5 Nov 2018 Arab American Frontiers 2018

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

PharmacoMicrobiomics

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

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

5 Nov 2018 Arab American Frontiers 2018

¡  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

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