What We Do
The Stromal-Immunoengineering Lab (SIEL) uses animal models, biomaterials, and single-cell methods to study immune–stromal crosstalk in tissue fibrosis and regeneration.
We focus on how inflammatory signaling between fibroblasts and immune cells drives cellular heterogeneity in health and disease. Single-cell analysis lets us identify clinically relevant cell subpopulations and phenotypes, revealing mechanisms that underlie disease and pointing to new therapeutic targets.
What Is a Stromal Cell
Stromal cells comprise much of the connective tissue in the body and secrete the extracellular matrix, which is the support system for cells and tissues throughout the body. The most common stromal cells are fibroblasts and pericytes.
Emerging evidence has shown that stromal cells have an influence over the immune response, and in different cases they can suppress or exacerbate an immune response. Scroll down to look at all the different ways we are investigating the interactions between stromal and immune cells!
Endometriosis affects 10% of reproductive-aged women but is underfunded and plagued with misconceptions. Symptoms like severe pain, abnormal menstruation, and infertility are often trivialized, resulting in an average diagnostic delay of 7 years. Characterized by ectopic uterine tissue (lesions, shown above), endometriosis is diagnosed via laparoscopic surgery, which fails to detect 20% of deep tissue growths driving inflammation and fibrosis. Treatments, which limit hormonal fluctuations, force patients to choose between pain relief and fertility, but still remain ineffective for one in every five cases.
A major challenge in addressing endometriosis is the heterogeneity of lesions, both between and within individuals. Lesions vary by location in their stromal compartments, immune responses, and fibrotic markers, complicating efforts to develop universal diagnostics or treatments. However, inflammation and fibrosis are hallmarks across all lesions.
To address this gap, we are investigating how fibroblasts in endometriosis lesions interact with immune cells, contributing to dysregulated immunity. Understanding these mechanisms could reveal novel pathways for improving diagnostics and treatments for endometriosis.
Idiopathic pulmonary fibrosis (IPF) is a fatal disease marked by the dense buildup of scar tissue in the lungs with no known cause or lasting cure. The prevalence of this disease continues to rise globally, with up to 45.1 cases per 100,000 persons and a poor prognosis with a 3–4-year median survival time following diagnosis. Common histopathological indicators of IPF are marked by areas of active fibrogenesis known as fibroblastic foci which comprise concentrated regions of myofibroblasts and newly synthesized ECM. Various immune and inflammatory markers are implicated to be highly expressed in these fibrotic regions. However, the distinct inflammatory pathways that elicit pathogenic fibroblast subpopulations and their respective locations within diseased tissue remain unclear and present challenges in diagnosing and treating IPF.
To decipher the mysteries surrounding IPF, we are identifying upregulated inflammatory pathways in active sites of fibrosis to determine the best therapeutic targets. Our lab is accomplishing this objective by using integrated in vivo and multi-omic approaches.
Approximately 50% of childbearing women suffer from pelvic organ prolapse (POP), where weakening of the pelvic floor muscles result in the abnormal descent of pelvic organs. Symptoms include chronic pain, urinary difficulties, and sexual dysfunction. Moreover, it has an estimated surgical cost of over $1.5 billion annually in the U.S. While the uterosacral ligament suspension (USLS) is a common surgery to re-suspend the uterus using the patient's own native tissue, it is plagued by up to a 40% failure rate.In collaboration with the Caliari Lab, we are developing a novel biomaterial to support the existing surgery to treat POP. This material aims to improve tissue integration at the uterosacral ligament-vagina interface created by surgery and thus reduce the risk of prolapse recurrence.
