More specifically, they seek to understand macrophage biology and its role in regenerative medicine strategies for tissue reconstruction. They have demonstrated that macrophage phenotype, and the ability of macrophages to switch polarization profiles in particular, plays a determinant role in outcomes following placement of biomaterials and tissue engineered constructs. Through development of a more in-depth understanding of immune interactions, they seek to engineer next generation solutions that control the temporal and spatial progression of the immune response and improve outcomes of regenerative medicine based therapies.
Charleen T. Neural Tissue Engineering: Dr. Specific projects include: 1 biomimetic surface coatings for neural microelectrode arrays to improve chronic neural recordings and stimulation stability, reliability and longevity; 2 micro-patterning of biochemical, surface chemical and electrical cues on electrode arrays for neural network study; 3 controlled drug delivery and biochemical sensing in the nervous system; and 4 control of neural stem cell growth and differentiation via surface and electrical cues.
Biomechanics: Dr. Cells and tissues are shaped by both mechanical forces and chemical signals during early development to produce the basic body plan and establish functional organs.
His group takes a multi-level experimental approach to reverse-engineer these processes combining classical embryological and modern cell biological methods with advanced engineering tools. His current research interests are in cellular therapy and graft engineering, the role of stem cells in neoplasia, and immunotherapy for metastatic cancer, projects he pursues with his scientific and life partner Dr. Vera Donnenberg. He is an internationally recognized expert in therapeutic cell processing and flow cytometry. Donnenberg has co-edited two editions of the CRC Handbook of Human Immunology and has authored more than scholarly publications.
Genetic Diversity in Liver Development and Regeneration: Research in the Duncan lab focuses on liver development, homeostasis and regeneration. Polyploidy is a defining feature of the adult liver. Hepatocytes are either mononucleated or binucleated, and ploidy is determined by the number of nuclei per cell as well as the ploidy of each nucleus. Although hepatic polyploidy has been described for well over years, the functional role of hepatic polyploidization is unclear. Moreover, in rodent models, chromosome-specific aneuploid hepatocytes were shown to play a specialized role in liver regeneration, promoting adaptation and resistance to different forms of chronic injury.
Program Faculty Profiles
Current studies explore mechanisms of hepatic polyploidy and aneuploidy, and effect on human health and disease. Development and Regeneration in the Eye: Dr. Their three major research foci are: 1 Epigenetic regulation of retinal development, 2 retinal pigment epithelium regeneration, and 3 optic cup morphogenesis and choroid fissure closure. While these topics may seem broad, I think this makes for a very stimulating environment for Ph.
We regularly publish in each of these areas. Smart Biotechnology for Immunotherapeutics and Tissue Engineering: The Little lab explores new strategies to regenerate tissues by presenting biological stimuli in a way that mimics that of native cells. Researchers in his group have developed new ways to synthetically reproduce complex, temporo-spatial presentation of bioactive molecules by design. A wide array of nano and micro fabrication techniques are used to promote proper spatial context.
Through key advances in the area of rational design, they have discovered ways to precisely tune a delivery vehicle to produce complex release behavior for the first time. Her group utilizes mouse models to examine the genetic etiology of CHD and validates these findings with human clinical studies. Their focus is also on the cellular and molecular basis of early cardiac development and on the developmental etiology of CHD.
Kacey G. The potential of adult stem cells derived from discarded fat, or adipose tissue, in regenerative medicine is immense and significant. In Dr. They characterize the ASCs using flow cytometry, and by differentiation into multiple phenotypes, and utilize ASCs for soft tissue and nerve regeneration, as well as wound healing with the eventual goal of clinical translation.
Liver Regeneration: Dr. Michalopoulos and his team are correlating liver regeneration to the development of therapies for liver failure and liver cancer. Simultaneous inhibition of the two mitogenic receptors for hepatocytes and stimulation of liver regeneration leads to liver failure. Genomic alterations highly prevalent in liver cancer are associated with growth suppressor pathways in normal hepatocyte growth.
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The evidence obtained from high-density genomic analysis of liver cancer cases has now implicated genes such as LSP1, PTPRD, MAML2 and RSU1 as essential growth suppressor pathways, which are involved in termination of liver regeneration and regulation of liver weight. Another protein, Glypican-3, highly over-expressed in liver cancer, regulates Hedgehog and Hippo pathway which controls YAP, an important protein in hepatocyte growth and liver size regulation. Liver regeneration has defined processes involved in organ growth with rich details not available in other organs and provides a framework to interpret cancer genomics in the context of normal tissue growth.
They investigate liver development to examine how cellular and molecular cues direct the expansion and differentiation of bipotential hepatic progenitors. Elucidating these mechanisms may be helpful in differentiating stem cell to hepatocytes. They also focus on the process of liver regeneration.
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Identification of molecular and cellular mechanisms that restore liver size will be of essence in treatment of liver insufficiency and form the basis of hepatic regenerative medicine. Her goal is to ultimately apply my knowledge to the development of improved diagnostics and clinically relevant therapies in the treatment of cholestatic liver disease, particularly primary sclerosing cholangitis — a condition with a significant unmet clinical need. Stem cells, germ lineage development, fertility and infertility: Research in Dr. Their progress investigating reproductive function in fertile individuals provides a basis for understanding the mechanisms of infertility caused by disease, medical treatments, genetic defects or aging.
Theirr lab is ideally located in Magee-Womens Research Institute and Magee-Womens Hospital of the University of Pittsburgh and is committed to translating lab bench discoveries to the clinic for diagnosis, prevention and treatment of infertility. In addition to fundamental investigations of ovary and testis development, their lab is actively developing stem cell therapies for male infertility and screening drugs that protect the ovaries from the damaging effects of chemotherapy. The overall research focus of Dr. Specifically, he and his team are aiming to:.
Synthetic Biology and Engineered Living Systems: The field of synthetic biology in recent years has had a renewed focus on reprogramming gene networks and cellular signaling. The Ruder lab is developing new approaches in synthetic biology and linking these technologies with engineered systems that mimic cell, tissue, and organism physiology. Research areas include the development of: 1 a living, bacterial microbiome for a biomimetic, robotic host, 2 artificial and engineered living microbiome constituents that deliver nutrients within organ-on-a-chip systems, 3 synthetically engineered cells that control material assembly, and 4 a biomimetic biofilm that combines microfluidics with synthetic biology to enable the discovery and monitoring of spatially segregated phenotypes within cell populations.
These systems hold significant promise for both elucidating fundamental principles of physiology while also serving as new technologies for biotechnology and medicine.
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Liver Development and Regeneration: Dr. Shin uses zebrafish as a model organism to understand liver development and regeneration at cellular and molecular levels. Using genetic tools that allow temporal manipulation of signaling pathways in zebrafish embryos, they investigate these processes.
They have recently developed a regeneration model in zebrafish that allows for temporal ablation of hepatocytes during any developmental period.
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Using this model, they have been investigating the cellular and molecular mechanisms of liver regeneration. They will perform a chemical screen using zebrafish embryos to identify compounds that can augment or repress liver regeneration. Cardiovascular Mechano-Energetics and Structure-Function Relationships Our research interests are focused on three areas: 1 Relationships between left ventricular mechano-energetic function and underlying cellular processes, with a special emphasis on contractile and regulatory proteins and post-translational regulation of cardiac contraction e.
Whole heart, isolated muscle, and single cell experiments are performed using various animal models, including transgenic mice. We are currently using this basic information regarding structure-function relationships to develop novel inotropic therapies that are based on altering cellular composition using genetic means and to optimize the fabrication protocol for engineered cardiac tissue such that it possesses the desired contractile and energetic properties.
Computational Biomechanics of the Brain; Application to Neuroimage Registration
One of the hypotheses being investigated is that aberrant vascular stiffness changes are involved in the genesis of certain cardiovascular pathologies e. Novel noninvasive measurement techniques are used to conduct longitudinal human studies, which are complimented by in vivo and in vitro vascular and cardiac studies with animal models. In addition to basic research, we have developed and continue to develop novel, simulation-based material i. His laboratory works on liver cell differentiation and understanding liver cell maturation of embryonic or induced pluripotent stem cells using interactions with liver non-parenchymal cells, 3D-liver extracellular matrix and different molecules to produce transplantable tissue or modeling diseases e.
Her research utilizes predominantly cell-based, scaffold-free tissue engineering where cells can generate and organize their own 3D structure and have the capacity to self-assemble into spatially organized multi-tissue structures. She engineers these tissues for use as implantable devices for therapy and models of tissue development or disease.