research

Sina Gharib

Assistant Professor of Medicine

MD

Faculty Web Page

Last Updated:  September 9, 2010

 

Research Focus

For much of the past century, basic research in biology has followed a reductionist paradigm whereby the focus has been on identifying a single molecule, pathway or model to explain complex phenotypes. While in many cases successful, this approach ignores the global consequences of such targeted perturbations. Our lab is interested in developing methodologies to integrate large-scale data interrogation (derived from transcriptional profiling, shotgun proteomics, or genome-wide assessment of genetic variants) with pathway-focused analysis to identify novel mechanisms in complex diseases. Through collaborative efforts, we are applying these systems-based strategies to better understand the pathophysiology of several disorders including acute lung injury, pulmonary hypertension, asthma, cystic fibrosis, malaria, and sleep disordered breathing.

Relevant Publications

Gharib SA, Luchtel DL, Madtes DK, Glenny RW. Global Gene Annotation Analysis and Transcriptional Profiling Identify Key Biological Modules in Hypoxic Pulmonary Hypertension. Physiological Genomics. 22(1):14-23, 2005.

Gharib SA, Liles WC, Matute-Bello G, Glenny RW, Altemeier WA. Computational Identification of Key Biological Modules and Transcription Factors in Acute Lung Injury. American Journal of Respiratory and Critical Care Medicine. 173(6):653-8, 2006.

Lovegrove F*, Gharib SA*, Patel SA, Hawkes C, Kain KC, Liles WC. Expression Microarray Analysis Implicates Apoptosis and Interferon-responsive Mechanisms in Susceptibility to Experimental Cerebral Malaria. American Journal of Pathology. 171(6):1894-903, 2007.

Seng KY, Glenny RW, Madtes DK, Spilker ME, Vicini P, Gharib SA. Comparison of Statistical Models for Identifying Differentially Expressed Genes Using Maximum-likelihood Analysis of Microarray Data. Gene Regulation and Systems Biology. 2:125-139, 2008.

Chang DW*, Hayashi S*, Gharib SA*, Vaisar T, King ST, Tsuchiya M, Ruzinski JT, Park DR, Matute-Bello G, Wurfel MM, Bumgarner R, Heinecke JW, Martin TR. Proteomic Analysis of Sequential Lung Lavage Proteins during the Acute Respiratory Distress Syndrome. American Journal of Respiratory and Critical Care Medicine. 178(7):701-9, 2008.

Gharib SA, Liles WC, Klaff L, Altemeier WA. Non-injurious Mechanical Ventilation Activates a Pro-inflammatory Transcriptional Program in the Lung. Physiological Genomics. 37(3): 239-48, 2009.

Gharib SA, Vaisar T, Aitken ML, Park DR, Heinecke JW, Fu X. Mapping the Lung Proteome in Cystic Fibrosis. Journal of Proteome Research. 8(6):3020-8, 2009.

Hancock DB*, Eijgelsheim M*, Wilk JB*, Gharib SA*, Loehr LR, Marciante KD, Franceschini Nora, van Durme Y, Chen T, Barr RG, Schabath MB, Couper DJ, Brusselle GG, Psaty BM, van Duijn CM, Rotter J, Uitterlinden AG, Hofman A, Punjabi NM, Rivadeneira F, Morrison AC, Enright PL, North KE, Heckbert SR, Lumley T, Stricker B, O’Connor GT, London SJ. Meta-analyses of genome-wide association studies identify multiple novel loci related to pulmonary function: the CHARGE consortium. Nature Genetics. 42(1):45-52, 2010.

Khalyfa A*, Gharib SA*, Kim J, Dayyat E, Snow AB, Bhattacharjee R, Kheirandish-Gozal L, Goldman JL, Gozal D. Transcriptomic Analysis Identifies Phosphatases as Novel Therapeutic Targets for Adenotonsillar Hypertrophy of Pediatric Sleep Apnea. American Journal of Respiratory and Critical Care Medicine. 15;181(10):1114-20, 2010.

Gharib SA*, Dayyat EA*, Khalyfa A*, Kim J, Clair HB, Kucia M, Gozal D. Intermittent Hypoxia Mobilizes Bone Marrow-derived Very Small Embryonic-like Stem Cells and Activates Developmental Transcriptional Programs. Sleep (in press).

*Co-First Authorship

 

Active Funding

Funding source

Project Title

Investigator Role

Funding dates

American Sleep Foundation

Mapping the Brain's Transcriptional Response during Sleep Disordered Breathing

PI

7/2009 - 6/2011

NIH

Mechanisms in the Remodeling of Lung Structure

Co-investigator

9/2008 - 8/2013

NIH

Regulation of Pulmonary Inflammation by Leukocytes and Extracellular Matrix

Co-investigator

7/2010 - 6/2015

NIH

E-cadherin Shedding in Chronic Lung Injury

Co-investigator

12/2009 - 11/2014

NIH

Stromelysin-2 in Lung Inflammation

Co-investigator

12/2010 - 11/2015


Current Mentees

Name

Degree

Project

Mimi Nguyen

PhD

Biomarkers for Ventilator Associated Pneumonia

Maryam Rohani

Post-doc

Role of MMP-1 in wound healing


Past Mentees

Name

Degree

Current title

Location

Kok Yong Seng

PhD

Research Scientist

Singapore


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