beth israel deaconess medical center a harvard medical school teaching hospital

To find a doctor, call 800-667-5356 or click below:

Find a Doctor

Request an Appointment

left banner
right banner
Smaller Larger

Carl J. Hauser, MD

 



Carl Hauser, MD

Lecturer on Surgery
Trauma Medical Director
Interim Chief, Acute Care Surgery, Trauma, and Surgical Critical Care

Research Group:

Christopher Barrett, MD
Arthur Celestin, MD
Elzbieta Kaczmarek, PhD
Haipeng Li, MD
Nicola Sandler, MD

Research Interests:

Trauma Surgery
Critical Care Surgery

Contact                        

 

 

  | Research Focus Research Support Publications |         

Research Focus:

The major research focus of my research is clinical inflammation biology. My lab is especially interested in the role of cellular Damage molecules, or “damage-associated molecular patterns” (DAMPs, aka “alarmins”) in inflammation. Our laboratory is a world leader in investigating the role of intracellular DAMPs derived from mitochondria. Our original work on this subject was published in Nature (March 4, 2010) and was widely cited as a groundbreaking conceptual advance in sepsis and inflammation research.

The known mitochondrial DAMPs include mitochondrial DNA, formyl peptides, some of the mitochondrial lipids, and other peptides that we are currently delineating. Mitochondrial DNA is a potent activator of toll-like receptors (TLRs), especially TLR-9. Signaling downstream from this receptor may be critical in the suppression of immune function after injury. Formyl peptides (FPs) are potent chemo attractants. They are also critically important activators of immune responses to damaged tissue, including wound debridement and the initiation of healing. On the other hand, however, these molecules may compete for the immune system’s “attention” in systemically injured patients. Thus also the innate response to FPs released by injury may render the host susceptible to infection.

Our current work centers on molecular aspects of this dichotomy between the necessity of inflammation after injury and the susceptibility to infection it incurs. Molecular aspects of these problems that we study (and which participants can become expert in) include neutrophil signaling, chemokine biology (especially intracellular calcium flux signaling), the regulation of endothelial permeability in SIRS, and most recently the study of neutrophil extracellular traps (“NETs”). Current investigations and collaborations with external organizations include studies investigating formyl peptide DAMPs in the plasma of trauma and septic patients as well as patients with cancer. We are also studying small peptides that inhibit the formyl peptide receptor family. Current collaborations within the institution include work with my longtime colleague Kiyoshi Itagaki, PhD, and the labs of Leo Otterbein, PhD, and Wolfgang Junger, PhD.

Based upon this work, we received a Department of Defense grant three years ago and were subsequently awarded an NIGMS R01 grant based upon it. We have begun to work with bioengineers to create “PCR-on-a-chip” assays to discriminate sepsis from SIRS based on this model, and were awarded a CIMIT grant to further that translational collaboration. We believe the central mechanisms we have discovered are a solid basis for large-scale collaborative research and have been begun work on a P50 Research Center Grant proposal. We have just submitted our first multi-PI grant with Leo Otterbein, PhD, and plan to extend this into a P50 Center Grant in collaboration with three other inflammation laboratories (James Lederer, PhD, Wolfgang Junger, PhD, and Michael Yaffe, MD, PhD) — all powerhouses on the Longwood campus.

Research Support:

Mitochondrial DAMPs and inflammation after injury;
NIH, 2010-2014; PI: Carl J. Hauser, MD

Prospective study of the tissue-resident regulatory
T-cell (Treg) function in clinical surgery; Tempero
Pharmaceuticals, Inc., 2011-2014; PI: Carl J. Hauser, MD

Activation of innate immunity by surgery and injury;
Department of Surgery Affinity Research Collaborative
(ARC), 2013-2014; PI: Carl J. Hauser, MD

The study of immunogenic non-formylated mitochondrial
peptides in acute surgical illness; Foundation grant by
BioMerieux SA, 2013-2014; PI: Carl J. Hauser, MD

Novel small-molecule inhibitors of formyl-peptide
receptors; Polyphor Pharmaceuticals, 2013-2014; PI: Carl
J. Hauser, MD

Harvard Trauma Inflammation T-32 Training Program;
NIH, 2013-2018; Co-Director: Carl J. Hauser, MD
(Director: Wolfgang Junger, PhD)

Publications:

Peer-Reviewed Publications in Print or Other Media

Davidson BA, Vethanayagam RR, Grimm MJ, Mullan BA, Raghavendran K,
Blackwell TS, Freeman ML, Ayyasamy V, Singh KK, Sporn MB, Itagaki K, Hauser CJ, Knight PR, Segal BH. NADPH oxidase and Nrf2 regulate gastric aspirationinduced inflammation and acute lung injury. J Immunol 2013;190(4):1714-24.

Sun S, Sursal T, Adibnia Y, Zhao C, Zheng Y, Li H, Otterbein LE, Hauser CJ, Itagaki K. Mitochondrial DAMPs increase endothelial permeability through neutrophil dependent and independent pathways. PLoS One 2013;8(3):e59989.

Sursal T, Stearns-Kurosawa DJ, Itagaki K, Oh SY, Sun S, Kurosawa S, Hauser CJ. Plasma bacterial and mitochondrial DNA distinguish bacterial sepsis from sterile systemic inflammatory response syndrome and quantify inflammatory tissue injury in nonhuman primates. Shock 2013;39(1):55-62.

Liu YJ, Siracuse JJ, Gage T, Hauser CJ. Phlegmonous gastritis presenting as portal venous pneumatosis. Surg Infect (Larchmt) 2013;14(2):221-4.

View more of Dr. Hauser's publications here.

Contact Information

Emergency: 911
Berenson Emergency Department: 617-754-2400
Acute Care Surgery Clinic: 617-632-9922
Trauma Program Office: 617-632-9916