Delano Lab

The Delano Lab, led by Dr. Matthew J. Delano, conducts basic and translational research across the fields of immunology and inflammation biology. Our work is focused on understanding the mechanisms responsible for long-term immune cell dysregulation and immune suppression associated with trauma, sepsis and chronic inflammation. More specifically, we're investigating the impact of diabetes and obesity on immune function and organ damage and failure following traumatic injury and sepsis. Understanding the role these comorbidities play will help us improve outcomes among our most vulnerable patients.

Through our clinical practice in acute care surgery, we see firsthand how traumatic injuries impact and are impacted by comorbid obesity and diabetes. Through our lab, we use preclinical models to investigate why problems such as persistent infection, organ injury and organ failure occur in trauma patients. We also screen and test targeted therapies to mitigate those consequences. Our goal, put simply, is to identify the particular cellular-level defects driving these long-term problems and find therapies to treat, if not prevent, them.

In the United States alone, traumatic injury leads to more than 40 million emergency department visits and over 2 million admissions annually. Within one month of the initial injury, the mortality rate hovers at about 3 percent. One year later, however, that figure rises to about 20 percent. Among individuals with Type 2 diabetes mellitus (T2DM) and obesity, the mortality rate doubles. Among patients who develop sepsis and septic shock , the mortality rate rises to a staggering 60 to 80 percent. And, in spite of over 100 clinical trials of single-agent sepsis therapies, none have been shown to improve survival.

As elderly and obese populations grow globally, and as multidrug-resistant bacteria continue to emerge and take hold, mortality from sepsis among patients with T2DM will rise significantly in the coming years. The nature of the populations we're treating is changing, and that has compelled us to look in new ways not only at trauma and sepsis but also the interconnections with obesity and diabetes. Doing so is leading to new insights into the role of immunity in all of these.

Our work encompasses cellular, molecular and biochemical studies of innate and adaptive immune function, including of neutrophils, monocytes, macrophages, dendritic cells, lymphocytes and stem cell and immune cell precursors in both human and animal models of trauma and sepsis. The interactions between innate and adaptive immunity are numerous and complex, and we have hypothesized that related deficiencies lead to the poor outcomes we see, including in quality of life long after traumatic injury, especially in diabetic and obese patients.

As we learned more about innate and adaptive immunity in sepsis, we hypothesized that obesity and diabetes are in fact functional immune deficiencies and that these prevent patients from mounting an effective response in the face of trauma and sepsis, thereby leading to the significantly worse outcomes seen in these patients. Our work continues to unravel the precise cellular and genetic pathways involved and to identify existing and new therapeutic compounds to target them.

Our research group was the first to elucidate the role of myeloid derived suppressor cells (MDSCs) and their expansion in the setting of trauma and sepsis, showing that while beneficial immediately following trauma or sepsis, the persistence of MDSC expansion (including in cancer and other disease states) can suppress adaptive immunity. This contributes to ongoing catabolism, cancer-related cachexia and chronic infection. The work clarifying the role of MDSCs led us to look more closely at the role of adaptive immunity in sepsis, and we among the first to clarify the role of regulatory T and B cells in recovery from sepsis.