Our goal is to develop non-opioid, microbial based analgesics for understudied chronic pain conditions.

Our lab studies how the microbiome -- or the collection of microorganisms that live in and on the surface of the body -- interacts with the nervous system to promote pain and analgesia. To research these topics, we use cutting-edge approaches and closely collaborate with clinicians to ensure that our findings are translationally relevant. Specific disease focuses are described below.

Sickle Cell Disease

Sickle cell disease (SCD) is the most prevalent genetic blood disorder in the world. Individuals diagnosed with this condition suffer from both excruciating acute pain and chronic pain that often has no obvious cause. Our lab uses transgenic mice that maintain the exact same genetic mutation as patients to study pain in this disease. Information learned in mouse models is tested for translational importance through our long-standing collaborator, Dr. Amanda Brandow, Director of the Comprehensive Sickle Cell Disease Clinical and Research Program at the Medical College of Wisconsin. Critical discoveries from the lab include the following:

We determined that SCD-associated changes in gut bacteria and metabolites drive chronic pain in this condition. We also determined that the probiotic Akkermansia muciniphlia decreases chronic SCD pain.
We identified several members of the Transient Receptor Potential (TRP) channel family (e.g., TRPC5, TRPV4) as critical targets for chronic SCD pain management.
We observed structural abnormalities in the peripheral nerves of SCD mice and found that administration of neuropathic pain medications alleviated certain types of pain in these animals.

Endometriosis

Endometriosis affects over 10% of individuals born with a uterus. Pain and infertility are the two primary symptoms of this condition which is diagnostically defined by the presence of endometrial tissue outside of the uterus. Historically, endometriosis pain was thought to arise from these ectopic -- or outside of the uterus -- endometrial lesions. However, growing evidence suggests that the number and size of endometrial lesions do not correlate with pain reports and removal of these lesions fails to alleviate pain in a sub-set of patients. Our lab is now studying other potential drivers of endometriosis pain in order to develop better analgesics for this condition. Ongoing research projects include the following:

Molecularly characterizing the neurons that innervate the female reproductive tract in healthy and disease states
Exploring the relationship between the vaginal microbiome and endometriosis pain
Examining interactions between endometrial epithelial cells and sensory neurons in the diseased uterus and endometrial lesions

Fundamental Microbiome Biology

Over the past two decades, there have been hundreds, if not thousands, of studies that have hinted at the microbiome playing a role in many different diseases. Many of these studies reached their conclusions by comparing the number and types of bacteria in stool samples from a given patient population with the number and types of bacteria found in healthy control stool. Although these studies are an important first step, they do not address the causality of the relationship between the microbiome and disease. In other words, they don't address if the disease results from a change in the microbiome or if a change in the microbiome is purely a symptom of the disease and nothing more. Using mouse models, we are attempting to answer this question for the following chronic pain conditions:

Migraine headache
Chemotherapy associated chronic pain

In addition to these studies, we are also examining how antibiotics -- drugs that kill bacteria -- cause acute pain and increase susceptibility for the development of chronic gastrointestinal pain disorders like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).

We are fortunate to be funded by: