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Monaghan Lab

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Monaghan Lab

Dr. Sean Monaghan’s research attempts to understand why some critically ill patients get better and others do not by interrogating mechanisms of immune dysfunction.

As a resident under the mentorship of Dr. Ayala, Dr. Monaghan's research initially focused on the immune modulating protein PD-1 and its role in acute respiratory distress syndrome (ARDS). Now, the focus of his laboratory is on the role of alternative splicing in critical illness, particularly as it relates to the immune modulating proteins (PD-1, BTLA, CTLA-4).

Biography

Dr. Sean Monaghan is a trauma, critical care, and acute care surgeon at Rhode Island Hospital and a Clinical Assistant Professor of Surgery at the Alpert Medical School of Brown University.

Dr. Monaghan's undergraduate work was at Boston College and he received his M.D. from Rutgers-New Jersey Medical School in 2007. Dr. Monaghan completed his surgical residency at Rhode Island Hospital/Alpert Medical School of Brown University, which included two years of a Versaci Research Fellowship in Dr. Ayala's laboratory in the Division of Surgical Research from 2009-2011.

In 2015, Dr. Monaghan completed a Surgical Critical Care Fellowship at Beth Israel Deaconess Medical Center/Harvard Medical School and shortly thereafter joined University Surgical Associates and the Department of Surgery at Rhode Island Hospital.  He resides in Pawtucket, RI with his wife and 4 children.

Research Overview

We focus of understanding alternative RNA splicing in critical illness (sepsis, trauma, acute respiratory distress syndrome) leveraging animal models, human data sets, samples from critically ill patients, RNA sequencing and advanced computational biology methods

Research Statement

  1. Pathophysiologic changes present in ARDS cause alternative RNA splicing events

    RNA splicing is known to be influenced by physiologic conditions such as acidosis and hypoxia, both common in ARDS. We will investigate these conditions and the splicing protein U1-70K and the impact on the pulmonary endothelial barrier. We will utilize RNA sequencing, over-expression of U1-70K isoforms, and Electric Cell-substrate Impedance Sensing (ECIS) in this work.
  2. Utilize RNA sequencing data to diagnose critical illness

    RNA sequencing produces large data sets, our lab usually aims for 100 million reads per sample. There is incredible information in not only the data that aligns to the genome, but also the un-mapped reads. We attempt to analyze the data in unique was to give outputs that are relevant for clinical practice. Using the RNA sequencing data from blood samples in humans we will look at gene expression, alternative RNA splicing, antibody production, and pathogens. This data will be used to generate diagnostic and therapeutic tools.

Funded Research

 

Brown University DEANS Award “Immune Dysfunction in Critical Illness/Injury: Role of Alternative Splicing”

Principal Investigators: Sean Monaghan, MD & Will Fairbrother, PhD

Total Costs: $80,000

American College of Surgeons, C. James Carrico, MD, FACS, Faculty Research Fellowship for the Study of Trauma and Critical Care “Immune Dysfunction in Critical Illness/Injury: Role of Alternative Splicing”

Principal Investigator: Sean Monaghan, MD

Total Costs: $80,000

National Institutes of Health (NIH) Loan Repayment Program

Principal Investigator: Sean Monaghan, MD

Total Costs: $263,241

NIH-NIGMS Pilot Project from the CardioPulmonary Vascular Biology (CPVB) Centers of Biomedical Excellence (COBRE): “Alternative RNA Splicing of Endothelial Cell Adhesion Proteins (PECAM-1 and VE-Cadherin) in ARDS”

Principal Investigator: Sean Monaghan, MD   

Total Support: $25,000

NIH-NIGMS Junior Faculty CardioPulmonary Vascular Biology (CPVB) Centers of Biomedical Excellence (COBRE): “The Role of Alternative RNA Splicing in Endothelial Cell Barrier Dysfunction in Acute Respiratory Distress Syndrome”

Principal Investigator: Sean Monaghan, MD   

Brown Physicians Inc (BPI) Research Award “The Role of Alternative RNA Splicing in Endothelial Cell Barrier Dysfunction in Acute Respiratory Distress Syndrome”

Principal Investigator: Sean Monaghan, MD   

Total Support: $50,000

Brown Physicians Inc (BPI) Research Award “The Role of Alternative RNA Splicing in Endothelial Cell Barrier Dysfunction in Acute Respiratory Distress Syndrome”

Principal Investigator: Sean Monaghan, MD   

Total Support: $50,000

NIH-NIGMS Improving Sepsis Care with Deep RNA Sequencing Data (R35GM142638)

Principal Investigator: Sean Monaghan, MD

Total Support: $1,982,510

Brown University
Providence RI 02912 401-863-1000

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Monaghan Lab