Thank you for your interest in the Mammoto Lab at the Medical College of Wisconsin. Our research focuses on understanding the roles of angiogenesis—the formation, remodeling, and maintenance of capillary networks—in tissue regeneration, aging, disease pathogenesis, and mesenchymal stromal/stem cell (MSC)–based therapies. Our mission is to translate fundamental discoveries in angiogenesis into innovative therapeutic strategies to combat aging and age-related diseases and improve human health. To achieve this goal, we are pursuing the following translational research projects. We value meaningful scientific collaborations and opportunities to advance innovative research. For inquiries related to our research or potential collaborations, please feel free to contact us. We look forward to connecting with those who share our scientific interests and vision.
1. The role of angiogenesis in lung regeneration.
Although epithelium is a major player in organ development and regeneration, blood vessels also play crucial roles in these processes. We are trying to understand the mechanism by which endothelial cells control lung development, regeneration and aging using multidisciplinary approaches. To study the mechanism of angiogenesis in the lung, we have developed a unique method to implant hydrogel on the lung surface of a living mouse and successfully recapitulated lung-specific angiogenesis and various cellular interactions in the gel in both physiological and pathological conditions. Our long-term goal is to develop more effective angiogenesis-targeted strategies for lung regeneration.
Vascular niche in lung alveolar development, homeostasis and regeneration.
2. Mechanism of age-dependent decline in angiogenesis.
Aging is associated with impaired angiogenesis, which contributes to the increased susceptibility to age-related lung diseases such as chronic lung diseases. We are investigating molecular mechanism by which aging inhibits lung vascular and alveolar morphogenesis using various transgenic animal models. In addition to soluble growth factors, biophysical factors such as changes in cell size, ECM stiffness, stretching forces, and flow control endothelial cell growth and differentiation. However, the mechanosensitive mechanism of age-dependent decline in angiogenesis and lung alveolar morphogenesis remains unclear. Thus, we also focus on the mechanosensitive mechanism of age-related decline in angiogenesis using various in vitro systems and transgenic animal models.
3. Pulmonary hypertension.
Pulmonary hypertension is a devastating pulmonary vascular disease characterized by aberrant muscularization of the normally non-muscularized distal pulmonary arterioles. We investigate the mechanism by which endothelial signaling controls vascular smooth muscle cell behaviors. We are studying the mechanism by which endothelial signalings control smooth muscle cell behaviors using in vitro assays, a hypoxia-induced experimental PH model, and transgenic animal models.
4. Therapeutic implantation of biomaterial-free mesenchymal stem/stromal cell (MSC) pellet.
We fabricated implantable pellets of human MSCs from subcutaneous white adipose tissue without exogenous biomaterials or scaffolds. Subcutaneously implanted MSC pellets in immunodeficient NSG mice stably engraft and stimulate local host-derived capillary formation. MSC pellets continuously express a variety of angiogenesis-related factors in vivo and function as a “living drug” within the body. While MSC-pellet implantation has little effects on basic physiological parameters (e.g., body weight, blood pressure, hematocrit) without tumorigenicity, the implantation increases capillary density in specific organs/tissues of the recipient mouse. MSC-pellet implantation also restores post-ischemic capillary rarefaction and prevents tissue hypoxia. The MSC-pellet therapy we have developed can be further optimized by using MSCs derived from alternative tissue sources (e.g., bone marrow, umbilical cord, or placenta) and/or by employing genetically or chemically modified MSCs. Importantly, this platform can be leveraged not only to preclinically assess the in vivo functional fitness of human MSCs, but also to enhance the therapeutic efficacy of MSC-based therapies in humans.
Implantation of human mesenchymal stromal cell (MSC)-pellet for therapeutic angiogenesis.
The Mammoto Lab is composed of ailurophiles (enthusiastic cat lovers) and we are committed to improving the lives of cats as well!
