Carl J. Hauser, MD

Trauma Medical Director


Research Group

Kiyoshi Itagaki, PhD
Barbora Vlkova PhD
Quanzhi Zhang MD

Research Focus

The major basic science research focus of my research is clinical inflammation biology and the mechanisms and management of infection after injury and surgery. My lab is especially interested in the role of cellular “Danger” molecules, or “damage-associated molecular patterns” (aka “DAMPs” or “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). It has been widely cited as a groundbreaking conceptual advance in sepsis and inflammation research, and has been cited more than 1,000 times. The known mitochondrial DAMPs include mitochondrial DNA, formyl peptides, and some of the mitochondrial lipids. Our recent work has shown that mitochondrial formyl peptides act as potent DAMPs. They circulate in plasma after injury where they activate innate immune cells while simultaneously causing heterologous suppression of cell-surface G-protein coupled receptors for critically important chemoattractants like chemokines and leukotrienes. Mitochondrial DNA is also a potent agonist that targets toll-like receptor 9 (TLR-9) and we have found that it is also a potent activator of neutrophil (PMN) extracellular traps (“NETs”). Signaling downstream from this receptor, however, may result in tolerance and so plays a critical role in suppression of immune function after injury. 

Formyl peptides (FPs) derived from mitochondria are potent chemoattractants. As such, they are critically important activators of immune responses to damaged tissue, including phagocytic wound debridement and thus the initiation of healing. On the other hand, these molecules compete for the immune system’s “attention” in systemically injured patients. In work presented at the American Association for the Surgery of Trauma (AAST) we showed that innate responses to FPs released by injury render the host susceptible to infection by suppressing PMN surveillance of the lung after bacterial inoculation. In further work, we have now shown that only five of the 13 native mitochondrial FPs are active at the formyl peptide receptors. Having participated in the development of novel antagonists for the human and mouse formal peptide receptors (FPRs) we are doing studies that use this information to create tools for diagnosis and therapeutic intervention. 

Our current work, therefore, centers on modulating inflammation in a way that balances the need for inflammation after injury as an initiator of tissue repair and the susceptibility to infection that systemic inflammation incurs. Molecular aspects of these problems that we study (and which participants can become expert in) include neutrophil signaling, chemokine biology (intracellular calcium flux signaling), the regulation of endothelial permeability in SIRS, and the study of neutrophil 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.

Last year, our work on these critical innate immune mechanisms became the foundation of a large Department of Defense focused project award. This programmatic award addresses the role of DAMPs in creating susceptibility of wounded war-fighters to infection. Our multi-PI grant includes work with the laboratories of Leo Otterbein, PhD, Michael Yaffe, MD, PhD, Simon Robson, MD, PhD James Lederer, PhD and Danny Talmor, MD. All these are powerhouse on the Longwood campus and have grouped together as the Harvard-Longwood ("HALO”) consortium for translational biology. This collaborative program uses computational biology to address the interactive rolls of DAMPs like formyl peptides, mitochondrial DNA, heme, carbon monoxide, purine metabolites (ATP and adenosine), reactive oxygen intermediates, complement, with the changing physical-chemical environment of the lung over time to result in altered innate immune cellular phenotypes. These are then permissive of healthcare-acquired pneumonia.

Accomplishments 2016-2017

  • Served as Medical Director of Trauma Services, BIDMC
  • Achieved re-verification of BIDMC as an ACS Level 1 Trauma Center 
  • Founded the Harvard Longwood (HALO) consortium for translational inflammation biology
  • Distinguished Service Medal for contributions to Military Medicine by the Armed Forces of Columbia
  • Elected Founding Councilor for Clinical Studies, International Association for the Study of Danger Signaling
Visiting Professorships and Invited Presentations
  • Novartis Institute of Biomedical Research Seminars in Basic Science, Danger Signaling After Tissue Injury, Cambridge, MA
  • Plenary lecture, Mitochondrial DAMPS and inflammation, American Transplant Society, Frontiers in Inflammation Relevant to Transplantation
  • Plenary lecture, The biology of surgical site infections, the Surgical Infection Society, Palm Beach, FL
  • Plenary presentation, Application of exogenous PMN to the airway rescues bacterial overgrowth initiated by trauma DAMPs, The American Association for the Surgery of Trauma, Waikoloa, HI
  • Invited lecture, Crush injury: Mitochondria matter, The Society of Critical Care Medicine, Critical Care Congress, Honolulu, HI
  • Presidential address, Ownership, The Western Trauma Association, Snowbird UT
  • AAST Webinar, Danger signaling: An important new principle in trauma and surgical injury
  • Plenary presentation, A subset of five human mitochondrial formyl peptides mimic bacterial peptides and functionally deactivate human neutrophils (PMN), Western Trauma Association, Whistler, BC
  • Scott R. Petersen Distinguished Lectureship, Ownership, St. Joseph’s Hospital and Medical Center, Phoenix, AZ
  • The molecular biology of trauma, X Congreso International de Cirugia Y Trauma Vascular, Hospital Militar Central, Universidad Militar Nueva Granada, Bogota, Columbia
  • Management of trauma to the femoral vessels, X Congreso International de Cirugia Y Trauma Vascular, Hospital Militar Central, Universidad Militar Nueva Granada, Bogota, Columbia
  • Missed retroperitoneal vascular trauma in the age of damage control surgery, X Congreso International de Cirugia Y Trauma Vascular. Hospital Militar Central, Universidad Militar Nueva Granada, Bogota, Columbia
  • Keynote presentation, The role of DAMPs in human injury, International Association for the Study of Danger Signaling, Guanajuato, Mexico
  • Keynote lecture, The role of danger molecules in susceptibility to infection and therapeutic opportunities, Symposium on DAMP-mediated remote organ failure and immunosuppression in the acutely ill patient: Where Trauma meets Sepsis, Faculté de Médecine, Strasbourg, France
  • Keynote lecture: DAMPS and PAMPS and why they matter in critical intra-abdominal injury/illness, The Abdominal Compartment Society, Banff, Alberta, Canada
  • The global impact of abdominal sepsis on human health, The Abdominal Compartment Society, Banff, Alberta, Canada
  • Future advances in modulating the inflammatory response in the peritoneal cavity: What will be needed? The Abdominal Compartment Society, Banff, Alberta, Canada
  • Activation of clinical inflammation by mitochondrial DAMPs, Queen Mary Hospital Trauma Science Colloquium, London, England

Teaching, Training, and Education

I am involved in teaching trainees at all levels, including Harvard Medical School students, General Surgery residents, and fellows in our accredited Surgical Critical Care Fellowship Program. In addition, I participate in the Department of Surgery’s Clinical Research Program, serving as a mentor to residents conducting clinical research projects. I helped develop the curriculum for our Surgical Critical Care Fellowship Program.

Selected Research Support

DAMP-mediated innate immune failure and pneumonia after Trauma; Department of Defense Focused Program Award, 2016-2021; PI: Carl J. Hauser, MD

Harvard Trauma Inflammation T32 Training Program in Trauma, Burn, and Peri-operative Injury; NIH, 2013-2018; Co-Director: Carl J. Hauser, MD (PI: Wolfgang Junger, PhD)

HBI-002 to treat traumatic injury; NIH, 2017-2019 (PI: Stephen Gomperts, MD, PhD, MGH)

Selected Publications

Itagaki K, Riça I, Zhang J, Gallo D, DePrato M, Otterbein LE, Hauser CJ. Intratracheal instillation of neutrophils rescues bacterial overgrowth initiated by trauma damage-associated molecular patterns. J Trauma Acute Care Surg 2017;82(5):853-860.

Atefi G, Aisiku O, Shapiro N, Hauser CJ, Dalle Lucca J, Flaumenhaft R, Tsokos GC. Complement activation in trauma patients alters platelet function. Shock 2016;46(3 Suppl 1):83-8.

Sandler N, Kaczmarek E, Itagaki K, Zheng Y, Otterbein L, Khabbaz K, Liu D, Senthilnathan V, Gruen RL, Hauser CJ.  Mitochondrial DAMPs are released during cardiopulmonary bypass surgery and are associated with postoperative atrial fibrillation. Heart Lung Circ 2018;27(1):122-129.

Coimbra R, Kozar RA, Smith JW, Zarzaur BL, Hauser CJ, Moore FA, Bailey JA, Valadka A, Jurkovich GJ, Jenkins DH, Davis KA, Price MA, Maier RV. The Coalition for National Trauma Research (CNTR) supports the call for a national trauma research action plan. J Trauma Acute Care Surg 2017;82(3):637-645.

Barrett CD, Celestin A, Eskander MF, Fish E, Glass CC, Gospodinov G, Gupta A. Hauser CJ. Surgeon performed ultrasound in predicting wound infections: No collection, no infection. J Trauma Acute Care Surg 2016;80(2):229-36.