At the Center for Inflammation Science and Systems Medicine, our mission is to advance the understanding of the complex role of inflammation in health and disease and to develop innovative approaches for preventing, diagnosing, and treating inflammatory conditions.
What is Inflammation?
Inflammation is a natural part of the body’s reaction to injury and infection, and is essential the body’s healing process. The term “inflammation” refers to the complex process by which the body’s innate immune system responds to harmful stimuli such as trauma, toxins and invading pathogens such as bacteria and viruses.
Unfortunately, while inflammation is essential to survival and wound healing, based on a variety of factors including genetics, the regulation of inflammatory processes can be corrupted. This results in excessive and sustained systemic inflammation, wreaking havoc in patients either acutely or chronically.
What is NAMPT?
Garcia lab has found that extracellular NAMPT is a master regulator of innate immunity affecting many pro-inflammatory genes and proteins that participate in the inflammatory response. eNAMPT is a DAMP, or damage-associated molecular pattern protein, released from injured tissues and via binding to a key and powerful pathogen recognition receptor, Toll-like Receptor 4 (TLR4), to trigger the inflammatory response. When regulation of eNAMPT levels is impaired, the excessive blood levels of eNAMPT leads to profound and potentially disastrous systemic inflammation, organ damage and even cytokine storm.
In partnership with a biotech company, CISSM scientists have developed a “first in man” immune-based humanized monoclonal antibody (mAb), known as ALT-100. ALT-100 is designed to address the development of “unchecked inflammation” in a number of severe inflammatory diseases.
About the Center for Inflammation Science and Systems Medicine
The mission of the Center for Inflammation Science and Systems Medicine at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology is to advance the understanding of the complex role of inflammation in health and disease and to develop innovative approaches for preventing and treating serious inflammatory conditions with unmet needs.
The Center brings together experts from diverse fields to collaborate and drive interdisciplinary research that integrates systems biology, drug discovery, genomics, genetics and clinical medicine in order to improve the health outcomes of individuals affected by inflammation and to contribute to the larger goal of promoting health and wellness for all. A primary focus is to gain a deeper understanding of the function, regulation and secretion of a variety of proteins that influence the magnitude of inflammatory processes and to detail the direct effects on inflammation on cancer, organ fibrosis, senescence and aging. Importantly, the center is actively conducting genetic epidemiological studies in order to identify patient populations that at risk for developing inflammatory conditions or that drive severity of disease allowing for the selection of patients most likely to respond to expensive biologic treatments.
Center scientists are experts on inflammation, blood vessel permeability or leakiness, and in designing therapeutics that will dampen the untoward effects of unremitting inflammation. For example, our research has revealed that a protein called NAMPT acts as a master controller of this inflammatory process. We have developed a monoclonal antibody that neutralizes extracellular NAMPT. We have studied it in many disease contexts, including in critically ill patients with an acute illness called ARDS, or acute respiratory distress syndrome, as well as in chronic inflammatory and autoimmune disorders such as systemic lupus, inflammatory bowel disease, non-alcoholic fatty liver disease and hepatic fibrosis. In collaboration with medical centers and corporate partners, this antibody, ALT-100, is now in clinical trials as a treatment to reduce the severity of ARDS and improve survival, as ARDS carries a 40% mortality rate.
About the Director
Dr. Joe G.N. “Skip” Garcia, M.D., is a pulmonary and critical care physician-scientist who has gained international recognition for his significant contributions to the field. As an elected member of the prestigious National Academy of Medicine, Garcia directs the Center for Inflammation Sciences and Systems Medicine at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, in Jupiter, Florida. Having held prominent academic leadership roles at institutions such as Johns Hopkins University, the University of Chicago, the University of Illinois, and the University of Arizona, Garcia also serves as the associate vice president for UF Health Research.
Garcia is an expert in the fields of pulmonary medicine and critical care, with a focus on understanding the molecular and genetic basis of inflammation and inflammatory lung diseases such as acute respiratory distress syndrome (ARDS), pulmonary fibrosis, and radiation-induced lung injury. He holds an extensive portfolio of NIH grants and has co-authored more than 600 peer-reviewed articles. He is a dedicated mentor and educator, particularly of under-represented minorities. Many Garcia lab trainees have gone on to become academic leaders at prestigious institutions. Garcia is also actively involved in promoting diversity and inclusion in academic medicine, is actively exploring health disparities in vulnerable populations, and has received numerous awards for his efforts in this area.
NAMPT (nicotinamide phosphoribosyltransferase) is an enzyme that plays a crucial role in the biosynthesis of nicotinamide adenine dinucleotide (NAD), an essential molecule involved in various biological processes such as energy metabolism, DNA repair, and cell signaling. NAMPT converts nicotinamide (NAM) into nicotinamide mononucleotide (NMN), which is then used to generate NAD. In addition to its intracellular role, NAMPT can also be secreted into the extracellular space where it acts as a cytokine and is known as eNAMPT. eNAMPT has been shown to have pro-inflammatory effects and to play a role in regulating immune responses.
The extracellular form is known as eNAMPT. Inside the cell, eNAMPT functions as an enzyme that produces a critical protein called NAD, which is essential for cellular health and preventing senescence. However, when eNAMPT is secreted into the bloodstream, it acts as a cytokine, specifically a master regulator cytokine. This is fortunate because NAMPT is also a DAMP, or damage-associated molecular pattern protein, which is released from injured tissues and binds to pathogen recognition receptors, triggering an inflammatory response to protect the organism. Our research has shown that NAMPT is one of the most important DAMPs, as our antibody effectively reduces inflammation. Therefore, it’s crucial not to interfere with eNAMPT’s intracellular enzymatic activity.
Inflammation in Disease: Publications and Highlights
Our team has published dozens of papers on the causes of inflammatory injury and disease, and highlighted potential treatments. Several highlights of that work are below, grouped by disease indication.
Two recent studies show preterm births and obesity-related liver disease improve following treatment with a monoclonal antibody developed by Joe G.N. “Skip” Garcia, M.D.
Elevated levels of pro-inflammatory proteins called eNAMPT were found in the lungs and blood of people hospitalized with acute respiratory distress syndrome, or ARDS. A lack of effective treatments has been an ongoing problem.