The research program aims to advance cardiovascular biology and medicine by focusing on pluripotent stem cell-based modeling and therapy and by nurturing future leaders in regenerative medicine.

David Hackam’s laboratory focuses on necrotizing enterocolitis (NEC), a devastating disease of premature infants and the leading cause of death and disability from gastrointestinal disease in newborns. The disease strikes acutely and without warning, causing sudden death of the small and large intestines. In severe cases, tiny patients with the disease are either dying or dead from overwhelming sepsis within 24 hours. Surgical treatment to remove most of the affected gut results in lifelong short gut (short bowel) syndrome. The Hackam Lab has identified a critical role for the innate immune receptor toll-like receptor 4 (TLR4) in the pathogenesis of necrotizing enterocolitis. The lab has shown that TLR4 regulates the development of the disease by tipping the balance between injury and repair in the stressed intestine of the premature infant. Developing an Artificial Intestine A key goal is to create, in the laboratory, new intestines made from patients’ own cells, which can then be implanted into the patient to restore normal digestive function. This innovative design could transform child development and quality of life in necrotizing enterocolitis survivors without the risks of conventional donor transplant.

The Wang lab focuses on the signals that direct the differentiation of pluripotent stem cells, such as induced-pluripotent stem (iPS) cells, into hematopoietic and cardiovascular cells. Pluripotent stem cells hold great potential for regenerative medicine. Defining the molecular links between differentiation outcomes will provide important information for designing rational methods of stem cell manipulation.

The Grayson Lab focuses on craniofacial and orthopaedic tissue engineering. Our research addresses the challenges associated with spatio-temporal control of stem cell fate in order to engineer complex tissue constructs. We are developing innovative methods to guide stem cell differentiation patterns and create patient-specific grafts with functional biological and mechanical characteristics. We employ engineering techniques to accurately control growth factor delivery to cells in biomaterial scaffolds as well as to design advanced bioreactors capable of maintaining cell viability in large tissue constructs. These technologies are used to enable precise control of the cellular microenvironment and uniquely address fundamental questions regarding the application of biophysical cues to regulate stem cell differentiation.

The mission of the Elisseeff Lab is to engineer technologies to repair lost tissues. We aim to bridge academic research and technology discovery to treat patients and address clinically relevant challenges related to tissue engineering. To accomplish this goal we are developing and enabling materials, studying biomaterial structure-function relationships and investigating mechanisms of tissue development to practically rebuild tissues. The general approach of tissue engineering is to place cells on a biomaterial scaffold that is designed to provide the appropriate signals to promote tissue development and ultimately restore normal tissue function in vivo. Understanding mechanisms of cellular interactions (both cell-cell and cell-material) and tissue development on scaffolds is critical to advancement of the field, particularly in applications employing stem cells. Translation of technologies to tissue-specific sites and diseased environments is key to better design, understanding, and ultimately efficacy of tissue repair strategies. We desire to translate clinically practical strategies, in the form of biomaterials/medical devices, to guide and enhance the body's natural capacity for repair. To accomplish the interdisciplinary challenge of regenerative medicine research, we maintain a synergistic balance of basic and applied/translational research.

The Kunisaki lab is a NIH-funded regenerative medicine group within the Division of General Pediatric Surgery at Johns Hopkins that works at the interface of stem cells, mechanobiology, and materials science. We seek to understand how biomaterials and mechanical forces affect developing tissues relevant to pediatric surgical disorders. To accomplish these aims, we take a developmental biology approach using induced pluripotent stem cells and other progenitor cell populations to understand the cellular and molecular mechanisms by which fetal organs develop in disease.

Our lab projects can be broadly divided into three major areas: 1) fetal spinal cord regeneration 2) fetal lung development 3) esophageal regeneration

Lab members: Juan Biancotti, PhD (Instructor/lab manager); Annie Sescleifer, MD (postdoc surgical resident); Kyra Halbert-Elliott (med student), Ciaran Bubb (undergrad)

Recent publications:
Kunisaki SM, Jiang G, Biancotti JC, Ho KKY, Dye BR, Liu AP, Spence JR. Human induced pluripotent stem cell-derived lung organoids in an ex vivo model of congenital diaphragmatic hernia fetal lung. Stem Cells Translational Medicine 2021, PMID: 32949227

Biancotti JC, Walker KA, Jiang G, Di Bernardo J, Shea LD, Kunisaki SM. Hydrogel and neural progenitor cell delivery supports organotypic fetal spinal cord development in an ex vivo model of prenatal spina bifida repair. Journal of Tissue Engineering 2020, PMID: 32782773.

Kunisaki SM. Amniotic fluid stem cells for the treatment of surgical disorders in the fetus and neonate. Stem Cells Translational Medicine 2018, 7:767-773