Program Director: James Luketich
Co-PDs: Julie Phillippi and David Vorp
Title: Cardiothoracic Surgery Research Training Program
PI: Andrew Duncan
Title: Mechanisms of Liver Regeneration Induced by Acetaminophen Toxicity
Description: Liver disorders affect 30 million people in the United States and are the country’s 10th leading cause of death. To improve liver disease treatments, a better understanding of hepatocyte biology is required. The liver contains diploid and polyploid hepatocytes, with polyploids comprising nearly 50% adult human and 90% adult mouse hepatocytes. The functional differences between diploid and polyploid hepatocytes are poorly understood. We previously demonstrated that diploid hepatocytes facilitate rapid liver regeneration, but it remains unknown how diploid and polyploid hepatocytes respond to drug-induced injury. Acetaminophen (APAP) is a common analgesic that can cause acute liver injury, resulting in liver failure and death when taken in excess. When APAP overdose causes extensive centrilobular hepatocyte death, the liver undergoes compensatory proliferation and recovers if the ratio of necrosis to regeneration is low. To investigate the role diploid and polyploid hepatocytes in vivo, we utilize E2f7 and E2f8 liver-specific knockout mice (LKO) where E2f7 and E2f8 are deleted during postnatal development; these mice are functionally normal through 6-9 months of age but are depleted of polyploid hepatocytes (LKO livers are >70% diploid). Preliminary studies indicate that LKO mice enriched with diploid hepatocytes are less damaged and recover faster from APAP injury than wild-type (WT) mice enriched with polyploid hepatocytes. The Grantee shall investigate mechanisms of liver injury and regeneration during APAP-induced liver injury and failure. This project shall determine ploidy-dependent and ploidy-independent mechanisms of liver repair and regeneration following APAP overdose.
PI: Alisse Hauspurg
Co-I: Ramakrishna Mukkamala, Sanjeev Shroff, and Aman Mahajan
Title: Development of a smartphone-based device to detect fluid overload among postpartum women with hypertensive disorders of pregnancy
PI: Mo Ebrahimkhani and Samira Kiani
Title: Collaborative Research: RECODE: Directed Differentiation of Human Liver Organoids via Computational Analysis and Engineering of Gene Regulatory Networks
PI: Kacey Marra
Title: Development of an Implantable Medical Device for Human Extremity Nerve Injuries
PI: William Wagner
Co-PI: John Alcorn, Stephen Badylak, Louis Falo, William Federspiel, Neeraj Gandhi, Eric Lagasse, Steven Little, Alan Wells, and Cecilia Yates
PI: William Federspiel / Ryan Orizondo
Title: Omniphobic coating of extracorporeal life support systems for improved thromboresistance (Subaward)
PI: Louis Falo
Title: Engineering the Skin Immune System to Induce Systemic Immune Responses
Description: The skin functions as a potent immune organ, rendering the readily accessible cutaneous microenvironment an attractive target that can be locally engineered to induce and regulate systemic immune responses. Increasing age is associated with changes in immune function (immunosenescence) that result in increased susceptibility to diseases and poor vaccine responses in older adults. This proposal is designed to bring together very recent and significant advances in dermatology and skin biology to address critical problems in human health. Here, we specifically focus on the skin microenvironment and strategies for cutaneous immunomodulation. The overall approach is to utilize a clinically applicable dissolvable microneedle array delivery platform we have developed to locally engineer the highly adaptive and immunoresponsive skin microenvironment. Specifically, we propose to modulate local immune regulatory circuits in the skin to enable the induction and regulation of systemic immune responses. The studies we propose will investigate the effect of locally delivered immune modulators on the mechanisms underlying cutaneous immune regulation in young and aged skin. Importantly, our studies include translational studies using living human skin to enable the rapid advancement of novel cutaneous immunomodulation strategies into clinical trials. The proposed studies will result in a better understanding of skin immunobiology specifically relevant to the development of safe and predictable skin immunoengineering strategies to regulate systemic immune responses across the lifespan.
PI: Alejandro Almarza
Co-PI: Juan Taboas
Title: Polymer Scaffolds for Mandibular Condyle Cartilage Regeneration
PI: George Michalopoulos
Title: Inhibition of EGF Receptor Prevents and Reverses Non-Alcoholic Fatty Liver Disease
PI: William R. Wagner
Title: Support for Proof-of-Concept Studies in Regenerative Medicine
Description: This proposal provides support for proof-of concept studies for advancing the state-of-the-art in regenerative medicine. Successful studies will be positioned to compete for advanced studies with funding from Federal agencies. The proposal includes projects involving both clinical and academic researchers all of whom are active in the growing field of Regenerative Medicine.
PIs: David Vorp
Title: Preclinical Optimization and Design for Manufacturability of Immunoregulatory Tissue-Engineered Vascular Graft
