GLA Research Grantees

Study (2023): "Elucidating persistent symptoms after neurological presentation of Lyme disease"

The causes of chronic Lyme disease are poorly understood and there are still no standardized treatment strategies for patients. Emerging evidence suggests that part of the mystery may lie in how patients’ immune systems respond to infection. The immune system sometimes reacts in a way that is not helpful for recovery and some people’s genetics may make them more prone to having a strong and possibly harmful immune response. This project aims to determine if an elevated inflammatory molecule is connected to persistent symptoms and if gender plays a role. Dr. Strle's group will also examine if some patients are genetically predisposed to developing more severe and long-lasting symptoms. Findings from this research will lay the groundwork for more effective immune-based treatment strategies for patients with debilitating lingering symptoms of Lyme disease. Similar therapies have been very effective in treating patients with systemic lupus erythematosus and other immune and autoimmune diseases.

Study (2023): "Effects of B. burgdorferi induced innate immune memory on long term infection"

A person’s DNA is the genetic instructions that make each individual unique and a person's epigenetic program dictates how their genetic instructions are read. In this regard, Dr. Petnicki-Ocwieja has found that ozone treatment of immune cells dampens the severity and duration of inflammation triggered by Lyme bacteria in a mouse model of infection. Whether this happens in some patients as well is yet to be determined. This project aims to identify genes that influence epigenetic programming in mice and determine if the Lyme bacteria causes epigenetic reprogramming of cells in the bone marrow of mice. The results of this study might identify inflammatory biomarkers that if inhibited would reduce Lyme disease severity. This could open new possibilities for personalized treatment. Imagine having a treatment plan that's designed just for you, based on your unique epigenetic makeup. This could be a game-changer for those struggling with chronic Lyme disease.

Study (2021): "Examining the role of CCL3/4/5 in post-infectious Basal Ganglia Encephalitis"

Group A Streptococcal bacteria can cause a neuropsychiatric condition in children called Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS). Dr. Agalliu’s group has been uncovering the inflammatory changes in the brain that may drive this disorder. He found that the brain cells of mice infected with Streptococcal bacteria produced elevated levels of inflammatory molecules, which were also elevated in the blood of PANDAS/PANS patients. When antibodies were used to block these inflammatory molecules, it diminished brain inflammation in the mice.  Dr. Agalliu's lab will determine if targeting these inflammatory molecules will also diminish behavioral problems in mice. Successful completion of this work will lay the foundation for future non-human primate studies and eventually pilot human clinical treatment trials to alleviate OCD and other symptoms in PANDAS/PANS patients.

Study (2023): "Bartonella Detection and Treatment in Infection-Associated Microenvironments"

Bartonella infections can be very challenging to treat. This project aims to determine whether Bartonella remain outside cells, hide within cells, or accumulate in biofilms when they invade the brain and heart of patients. Where the Bartonella reside in tissues may influence how sensitive or resistant they are to antibiotics. Dr. Monica Embers will validate molecular tools that will specifically visualize Bartonella when present in patient tissues and determine which antibiotic combinations are most effective at killing Bartonella when they are inside cells or in biofilms. The treatments they will test will include doxycycline, gentamicin, rifampin, clarithromycin, azithromycin, and A-Bart. An important outcome of this study will be identification of drug combinations that can kill Bartonella, even when they are inside cells or in biofilms. Such knowledge will yield more effective treatment strategies for patients with chronic Bartonellosis.

Study (2023): "Elucidating the Microbiological and/or Host-Related Factors Underlying PTLDS"

Why some patients develop chronic Lyme disease is still unknown. One possibility is persistence of live antibiotic-tolerant bacteria or dead bacteria that accumulate in tissues and cause inflammation. Using a mouse model of Lyme disease, researchers will explore whether one or the other or both explanations are valid. The project aims to determine if round body forms of the Lyme bacteria are more antibiotic-tolerant and if growth within mammals increase the number of these persister bacteria. They will also test the sensitivity of persister bacteria to antibiotics like doxycycline, amoxicillin, ceftriaxone, azithromycin, and hygromycin A. Finally, they will use genetically altered Lyme bacteria that are fluorescent or bioluminescent to track their movement in infected mice and determine whether they die or remain alive, and for how long. The results of this study will help inform health care practitioners which antibiotics are effective against persisters and which are not. It also is anticipated that determining whether Lyme bacteria remain alive or die, will guide whether treatments should focus on killing the persisters or removing the inflammatory debris of dead Lyme bacteria.

Study (2021): “Cerebrospinal Immune Response in a Tractable Murine Model of Lyme Neuroborreliosis”

Lyme neuroborreliosis (LNB) occurs in 10–15% of Lyme disease cases. Although much progress has been made in diagnostic LNB research using clinical specimens, there is still an urgent need for a tractable animal model that can be utilized to study the pathobiology of LNB. Dr. Brissette’s team has developed a model of LNB using C3H mice, and their long-term goal is to utilize this model to identify pathogen, host, and environmental factors that trigger central nervous system involvement in order to develop new prophylactic and therapeutic treatments for LNB. Additionally, this study will determine markers of infection and/or inflammation in the cerebrospinal fluid (CSF) of infected mice, which could serve as inflammatory signals to the brain. Such biomarkers, if present in human CSF, might be indicative of continued infection.