Mind Body Genomics and Systems Biology: Underpinning the Mechanism of Relaxation

Response Manoj K. Bhasin, Ph. D.

Assistant Professor Of MedicineHarvard Medical School

Director Bioinformatics & Systems BiologyCo-Director, Genomics, Proteomics, Bioinformatics and Systems Biology Center

Beth Israel Deaconess Medical CenterBoston , MA

mbhasin@bidmc.harvard.edu

Mission and Vision

• Our Mission Is To Innovate And Implement Novel Approaches For Deciphering The Molecular Mechanisms of Mind-Body Interventions

Our vision is to use the power cutting edge omics and systems biology approaches to identify

pathways and key master molecules associated with RR

TEMPORAL GENOMICS CHANGES OF RR IN HEALTHY SUBJECTS CROSS-SECTIONAL AND LONGITUDINAL TEMPORAL DESIGN

PROGRESSIVELY UPREGULATED PATHWAYS:

• Mitochondria and energy metabolism• Electron transport chain• Insulin secretion

Higher Changes in N1 vs M as Compared to N1 vs N2

Bhasin et al , PLOS One , 2013

Systems Biology Network Analysis Of Upregulated Progressive RR Response Genes

Interactive network analysis of significantly modulated pathways identified mitochondrial ATP synthase (ATP5C1) and Insulin (INS) as top upregulated progressive focus hub genes

Interactive network analysis of Long term, Short term and Progressive RR downregulated genes

consists of many upstream and downstream targets of NF-kB

Pseudo color scale from red to green represents Bottleneck ranks from 1 to 20. Bottleneck rank is a

significance level with smaller rank indicating increasing confidence.

UNDERSTANDING THE MECHANISM OF R3P IN IBD/IBS

Prospective single center study

Baseline and week 9 assessments after R3P

Changes in Biological and Psychological metrics associated with IBD/IBS (e.g. IBDQ, IBSQ) and gene expression profile

Peripheral Blood Mononuclear Cells (PBMCs) from 19 IBS and 29 IBD patients obtained before (Pre RR) and after (Post RR) 9 weeks of RR

Transcriptional profiling

Systems Biology analysis of Transcriptome changes to identify key molecules

RR INDUCED SYSTEM LEVEL ALTERATIONS IN CELLULAR PROLIFERATION AND IMMUNE SYSTEM RELATED NETWORK IN IBD

primary regulatory nodes/molecules=UBC, MAPK8, NFKB and ERK1/2

Kuo and Bhasin et al, PLOS One, 2015

ANALYSIS OF NETWORK/PATHWAYS IDENTIFIED NFKB DOWNSTREAM AND CELL CYCLE LINKED MOLECULES AS KEY MOLECULES:

Kuo and Bhasin et al, PLOS One, 2015

Review of Mind-Body interventions effects in Diseased & Healthy States :

SUMMARY:

• The systems level analysis of RR data in healthy subjects provided first insight into multimodal effect of RR to relay its beneficial effects.

1. RR mediated upregulation of mitochondrial energy production through upregulation of ATPase and insulin function.

2. RR blunt down inflammation by down regulating up- and Down- stream molecules of NFKB.

• Systems Biology analysis suggested NF-kB as key molecules for ascribing beneficial effects of RR in IBD patients.

• Meta-analysis of MBI indicated downregulation of pro-inflammatory molecules and NFKB interactants as primary mechanism to deliver beneficial effects.