Deb Laboratory Research Interests
Our laboratory is broadly interested in understanding the biology of adult stem cells and specifically how they can be targeted to enhance organ regeneration and repair. We are investigating repair and regeneration in the heart, that represents a terminally differentiated organ and possesses a minimal ability to regenerate itself following injury. Moreover, we are studying signaling systems in the injured heart that regulate a regenerative response to tissue injury in contrast to a fibrotic one. Ongoing specific projects available for rotating students are as follows:
1) To determine the role of Wnts in cardiac fibrosis and regeneration following cardiac injury
Heart disease remains a leading cause of mortality and morbidity in the developed world and is an emerging public health problem in the developing world. The heart is unable to efficiently replace myocytes lost secondary to injury or a heart attack and heals itself by fibrosis. Ultimately this nonfunctioning scar leads to worsening cardiac performance and heart failure. We have identified several Wnts that appear to regulate vital components of the response to injury of heart tissue. Using transgenic and inducible mouse knockout models that we possess in our laboratory, we are currently investigating how the Wnt signaling system can be manipulated after cardiac injury to minimize cardiac fibrosis and induce myocyte regeneration. We hope that a deeper understanding of pathways that regulate fibrosis and regeneration will enable the design of novel therapies for preserving cardiac function after injury. Students will have an opportunity to form in-situ hybridization, immunostaining and Western blotting.
2) To study the cardiac stem cell niche and its alterations with cardiac injury
Using novel isolation and culture techniques, we have isolated “cardiospheres” from the adult mouse and rat heart. We have demonstrated that cardiospheres analogous to neurospheres are spherical clusters of cells, contain a mixture of undifferentiated progenitors and somatic cells and have the ability to differentiate into multiple cell lineages including myocytes, smooth muscle, fat bone etc. This has become an extremely useful system to study the cardiac “stem cell niche” in-vitro and we are currently investigating how injury in-vivo alters the cardiac stem cell niche, potency and formation of cardiospheres. This project could provide novel information into how disease alters stem cell niches within the adult heart. Students will have an opportunity to isolate cardiac stem cells and cardiospheres, perform differentiation experiments and analyze gene expression and morphology of differentiated cells.
3)To the determine the role of Wnts in regulating function of circulating human vascular progenitors
We have isolated both endothelial and smooth muscle progenitors (EPC, SPC) from human peripheral blood. Both EPCs & SPCs exhibit typical morphological and functional determinants of endothelial and smooth muscle phenotypes. Patients with diabetes and vascular disease have dramatically decreased EPC number and function. We have observed that several Wnts appear to significantly enhance EPC function and are currently investigating in various mouse models whether Wnts can be therapeutically employed to rescue dysfunctional EPC isolated from diseased subjects. Smooth muscle progenitors have been implicated to play a role in atherosclerosis and we are currently studying the role of the Wnt signaling system in regulating smooth muscle progenitor function in atherosclerosis. Our data sheds new light into the role of EPC and SPC in vascular disease and the role of Wnts in regulating their function in health and disease. Students will have the opportunity to isolate murine and human endothelial and smooth muscle progenitor cells and perform in vitro assays of function in murine models of injury.
(Our work is funded by the NIH, Ellison Medical Foundation & Medical Foundation of North Carolina.)