The faculty members of the program investigate aspects of tissue bioengineering, cellular and molecular mechanisms of human disease and regenerative processes. Brief descriptions of the faculty research interests appear below:
Dr. Abramowitch joined the MSRC family in 1999 as a graduate student. He received his BS (1998) in Applied Mathematics and PhD. (2004) in Bioengineering from the University of Pittsburgh. Currently, he is an Assistant Professor in the Department of Bioengineering and serves as the Co-Associate Director of the MSRC and Director of the Tissue Mechanics laboratory. In addition, Dr. Abramowitch holds a secondary appointment in the Department of Obstetrics, Gynecology, and Reproductive Sciences. In 2008, Dr. Abramowitch was awarded a Building Interdisciplinary Research Careers in Womens Health (BIRCWH) fellowship. The main focus of Dr. Abramowitch’s research is understanding the impact of pregnancy, delivery, and other life events (aging, menopause, etc.) on the structural integrity of the pelvic floor in women. The primary goals of the Tissue Mechanics laboratory are to 1) rigorously characterize normal, healing, and diseased soft connective tissues, 2) develop robust models that describe tissue function, 3) teach students and clinical fellows to conduct proper mechanical testing experiments and analysis.
Stephen Badylak, DVM, PhD, MD (Bioengineering, McGowan Institute, and Surgery)
Tissue Engineering, Biologic Scaffolds, and Extracellular Matrix Biology:
Dr. Badylak’s laboratory is focused upon the translation of tissue engineering and regenerative medicine principles to the clinical setting. Dr. Badylak has successfully implemented the use of biologic scaffolds composed of naturally occurring mammalian extracellular matrix (ECM) into human clinical practice. The present efforts of the laboratory include studies to better understand the signals that control the host response to implanted scaffold materials; especially biologic scaffolds. There are major efforts and active projects in the areas of composition and ultrastructure of the ECM/cell signaling, environmental cues that regulate host response to injury and tissue reconstruction, musculotendinous tissue reconstruction, and CNS reconstruction. In addition, there are intense efforts to understand the relationship of the host innate immune response to the remodeling events that occur following the implantation of biologic scaffold and synthetic scaffold materials. Clinical translation efforts are focused upon esophageal replacement in patients with Barrett’s Esophagus and the repair and reconstruction of musculotendinous structures. The lab is highly interdisciplinary and staffed by a rich mixture of biologists, engineers, chemists, physicians, and scientists.
Computational & Systems Biology:
Dr. Bahar will be advising on the use of computational models of different complexity for simulating dynamic processes at different levels. Her expertise is in the application of methods for reaction kinetics and machine learning to model and analyze the dynamics of cellular networks, and to develop computational tools for quantitative systems pharmacology. These approaches are becoming increasingly important with rapid accumulation of sequence, structure, & pathways data, and the growing need for personalized medicine tools.
Cardiopulmonary Organ Replacements:
The Brown laboratory is broadly focused on the role of host response in regenerative medicine approaches to tissue reconstruction. 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. The Brown Laboratory is increasingly focused upon the interplay between the host innate immune system and aging in the context of regenerative medicine, and the application of these concepts to women’s health.
Mechanisms of Mitochondrial Stress and Autophagic Remodeling in Neurodegeneration:
A long-term goal of Dr. Chu’s research is to understand mechanisms of oxidative neuronal injury and neurodegeneration, which can be therapeutically targeted to promote regeneration of functional circuits. They hypothesize that protective/reparative responses are activated during injury, but prove inefficient or maladaptive in certain contexts. Since neurons retain the capacity for neuritic/synaptic plasticity throughout the lifetime, identifying cellular mechanisms that tip the balance to favor regenerative remodeling represents a promising approach for neurodegenerative diseases. Their work is focused on understanding injury & repair mechanisms relevant to Parkinson’s disease, Lewy body dementia, environmental intoxications & hereditary parkinsonian syndromes, focusing on oxidative stress & autophagy.
Neural Tissue Engineering:
Dr. Cui’s research interests lie in neural engineering with special emphasis on the neural electrode-tissue interface, neural tissue engineering, CNS drug delivery and biosensors. 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.
Dr. Davidson’s research is focused on understanding the physical and chemical processes that shape embryonic tissues and organs. 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 group seeks to understand how the cytoskeleton, adhesion receptors and the extracellular matrix contribute to tissue mechanics & force generation during vertebrate morphogenesis. They use microscopy & image analysis techniques including fluorescent RNA in situ, FRET, photo-activation, & high-resolution time-lapse confocal imaging of live cells in tissues, computer simulations of developing embryos at the molecular, cellular and tissue scales.
Cancer Stem Cells:
Dr. Donnenberg holds appointments at the University of Pittsburgh School of Medicine as a Professor of Medicine with tenure, the University of Pittsburgh Graduate School of Public Health as Professor of Infectious Diseases and Microbiology, and he is a member of the McGowan Institute of Regenerative Medicine. 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. Dr. Donnenberg has co-edited two editions of the CRC Handbook of Human Immunology and has authored more than 200 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 100 years, the functional role of hepatic polyploidization is unclear. Dr. Duncan’s lab recently showed that regenerating polyploid hepatocytes undergo specialized cell divisions to form aneuploid daughter cells, generating a high degree of genetic diversity within the liver. 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. Current studies explore mechanisms of hepatic polyploidy and aneuploidy, and effect on human health and disease.
Relationship Between Reproduction and Aging:
Dr. Ghazi studied Drosophila muscle development as a graduate student while at the NCBS, TIFR, India. A chance encounter with the worm (and some cool aging biologists) got her interested in the fountain of youth. She did her post-doctoral work on the genetics of aging at the University of California, San Francisco. Her lab identifies and studies genes that determine the length of life and quality of aging using the model C.elegans. Research in her laboratory is supported by the National Institutes on Aging (NIA/NIH) and the Global Consortium for Reproductive Longevity & Equity (GCRLE). One of the major foci of the Ghazi lab’s research is the relationship between reproduction and aging. It is a well-known fact that increasing age reduces reproductive capacity, but there is now strong evidence that the health status and rate of aging of the reproductive system strongly influence the aging of the whole organism. We study genes that link reproductive health with lifespan and aspects of aging-related healthspan features such as immunity, mobility and neurodegeneration. The lab has identified novel mechanisms by which animals retain metabolic homeostasis and longevity in the face of reproductive perturbations. These physiological alterations are brought about by a group of conserved pro-longevity transcription factors- TCER-1, NHR-49 and DAF-16 (Ratnappan et al., 2014, PLoS Gen.; Amrit et al., 2016 PLoS Gen.). In a surprising and influential discovery, the lab demonstrated that TCER-1, that functions a longevity-enhancing factor in fact represses immunity, and appears to do so to divert resources towards reproductive fitness (Amrit et al., Nature Comm. 2019). These discoveries, and our studies on NHR-49 (Naim et al., Aging Cell, 2021) have created avenues to dissect the mechanisms linking fertility, lifespan and healthspan. TCER-1 is homologous to the human transcription elongation and splicing factor, TCERG1. Our preliminary studies have found that TCER-1 regulates the alternative splicing of germline genes with potential roles in reproductive aging. This is a truly exciting discovery because it has opened up avenues to study a role for mRNA splicing, an emerging hallmark of somatic aging, in determining the rate of reproductive aging.
Development and Regeneration in the Eye:
Dr. Gross’s research program focuses on ocular development, disease, and regeneration, and utilizes the zebrafish as a model system for most of the lab’s studies. 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 PhD students and postdocs in the group, and it attracts trainees who are generally interested in ophthalmology and human disease research, developmental biology and cell biology, and who want to have the freedom to go where their interests take them. We regularly publish in each of these areas.
Stem Cells, Liver Tissue Engineering:
Dr. Lagasse’s research focuses on the development of novel cell-based therapies for patients suffering from degenerative diseases using stem/progenitor cells. In addition, they have established a Cancer Stem Cell Center, a collaborative effort between the McGowan and the University of Pittsburgh Cancer Institute. Their current research includes: Identification, isolation, and characterization of stem cells for liver diseases; development of assays for stem cells; in vitro & in vivo expansion of stem cells; and the development of cell-based therapies for liver diseases.
Effective Treatments for Joint Diseases:
Dr. Lin received a BS in Biochemistry from the Nanjing University, Nanjing, P.R.China. He received a PhD in Cell Biology from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R.China. Dr. Lin was a Visiting Fellow at the National Institute of Arthritis and Musculoskeletal and Skin, National Institutes of Health, Bethesda, MD. He has been with the University of Pittsburgh since 2010, as a postdoctoral associate and a research assistaint professor. The goal of Lin Lab is to apply the latest biological knowledge and state-of-art technology in orthopaedic research and translate the research findings into effective treatments for joint diseases, particularly osteoarthritis (OA). Focusing on translational research, there are three integrated projects in Lin Lab: (1) investigating the association between aging and osteoarthritis using human samples and animal models; (2) establishing an in vitro microphysiological OA model for OA pathogenesis study and drug development; (3) testing the stem cell-based therapy for the repair of cartilage injury, including iPSCs and mesenchymal stem/stromal cells.
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. The mission is to utilize “bio-mimetic” delivery systems to achieve: 1) enhanced therapeutic efficiency and create progressive new therapies that “imitate life” & 2) understand basic biological processes that would otherwise be obscured without engineering tools to replicate the presentation of spatially correct molecular information that occur in these processes.
Cardiac Development and Congenital Heart Diseases:
Dr. Lo’s research objectives are to elucidate genetic causes and developmental mechanisms of human congenital heart disease (CHD). 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. Eventual goals are to develop more effective diagnostic & therapeutic strategies to improve the lives of patients with structural heart diseases.
Tissue Engineering Using Adipose-Derived Stem Cells:
Dr. Marra’s laboratory pursues cellular therapies using adult stem cells derived from human adipose tissue. The potential of adult stem cells derived from discarded fat, or adipose tissue, in regenerative medicine is immense and significant. As 65% of Americans are overweight, adipose tissue represents a plentiful, attractive, and reliable source for somatic cells. In Dr. Marra’s laboratory, they routinely isolate adipose-derived stem cells (ASCs) from human and animal fat. 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.
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. 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.
Liver Development, Stem Cells and Regeneration:
The major focus of Dr. Monga’s research is to develop novel therapies for liver insufficiency in acute or chronic liver failure. 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 study pathways like Wnt/b-catenin, FGF, Hippo and PDGFRa signaling in liver development. They also focus on the process of liver regeneration. 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. They are researching role of Wnt/b-catenin signaling pathway in liver regeneration process through use of multiple, sophisticated genetic mouse models and using chemical and hormonal modulators of this pathway to induce regeneration that is highly significant and translational.
Cellular and Molecular Basis of the Liver:
For the past 15 years, Dr. Nejak-Bowen’s research has been focused on understanding the cellular and molecular basis of liver health and disease. Specifically, she is interested in understanding the role of signaling pathways, such as Wnt/β-catenin in liver inflammation, injury, and cholestasis. Dr. Nejak-Bowen has recently identified a novel association of β-catenin with FXR that is unresponsive to bile acids or FXR agonists but sensitive to β-catenin inhibition. This causes synergistic activation of FXR in combination with an FXR agonist. She is also elucidating the role of β-catenin in transdifferentiation of hepatocytes to cholangiocytes during chronic biliary injury. 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. Orwig’s laboratory focuses on stem cells, germ lineage development, fertility and infertility. 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.
Cell migration, Cancer Biology, Signal Transduction, and Angiogenesis:
The overall research focus of Dr. Roy’s laboratory is studying the role of actin-binding proteins in cell migration and other actin-dependent processes in physiology and pathology at the molecular levels. Specifically, he and his team are aiming to 1.) understand the role of cytoskeletal proteins in the regulation of tumor growth, invasion and dissemination, metastatic colonization, and chemotherapy response of cancer cells; 2.) identify novel drugs that have potential to block specific steps of tumor metastasis using high-throughput/high-content screening strategies; 3.) identify novel anti-angiogenic compounds; 4.) understand molecular regulation of key controllers of cell migration; and 5.) elucidate BRCA1’s role in ovarian cancer metastasis. Most of his lab’s current efforts are centered on profilin-1, a ubiquitously expressed actin-binding protein that is essential for embryonic development and a key molecular regulator for actin dynamics in cells
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. Simultaneously, exciting technologies have allowed precise engineering of materials and devices that mimic cell’s native environment. 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.
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. 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.
Development of Therapeutics to Mitigate Acute Kidney Injury:
Dr. Sims-Lucas completed his undergraduate/PhD training at Monash University, Melbourne, Australia. He then spent 1 year at the Australian Stem Cell Center, before conducting his post-doctoral at The Ohio State University Followed by the University of Pittsburgh until 2012. Dr. Sims-Lucas is a basic research scientist, he is trained as an anatomist and developmental biologist. His research focuses on the formation of the kidney and the role of maternal stresses (including diabetes and malnutrition) on the formation of the kidney. Furthermore, his program focuses on acute kidney injury as well as the mechanisms that lead to predisposition to injury. The long term goal of Dr. Sims-Lucas’ research relates to the development of therapeutics to mitigate acute kidney injury. He has authored more than 60 publications and has an NIH R01 funded research program. He has a passion related to education and is the Director of Student Research Training at the Rangos Research Center and is integral in all levels of training including high school students, undergraduate students, graduate students and post-docs. Finally, he is also the Director of the Histology Core at the John G. Rangos Sr. Research Center.
Cardiovascular Mechano-Energetics and Structure-Function Relationships
The Shroff Lab’s 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.g., via phosphorylation or acetylation). 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. (2) The role of pulsatile arterial load (vascular stiffness in particular) in cardiovascular function and potential therapeutic applications of vascular stiffness-modifying drugs and/or hormones (e.g., relaxin). One of the hypotheses being investigated is that aberrant vascular stiffness changes are involved in the genesis of certain cardiovascular pathologies (e.g., preeclampsia, isolated systolic hypertension in elderly). 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. (3) The role of regional contraction dyssynchrony in global ventricular mechanics and energetics. In addition to basic research, we have developed and continue to develop novel, simulation-based material (i.e., mathematical models of biological systems and associated “virtual experiments”) for education and engineering design.
Organ Replacement, Regenerative Medicine Approaches:
Dr. Soto-Gutierrez’s research is focused on the development of new technologies for organ replacement using bioengineering, cell transplantation and organ engineering. His lab uses the structural connective tissue of discarded organs as a scaffold for growing new tissue/organs for transplantation. 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.g. fatty liver). In addition his laboratory is interested in strategies for liver repopulation & regeneration in disease states (e.g. liver failure and liver steatosis) and hybrid organ engineering for transplantation to treat diabetes.
Scaffold-Free Tissue Engineering Approaches:
Dr. Syed-Picard’s research group focuses on stem cells and tissue engineering. 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. A major focus of the Syed-Picard research group is to uncover mechanisms of tissue patterning seen in these engineered tissues. Dr. Syed-Picard uses several engineering tools to study these constructs including advanced microscopy and microfluidic devices. She is working to regenerate dental tissues and peripheral nerve.
Computational and Systems Biology; Drug Discovery Institute:
Dr. Taylor applies quantitative systems pharmacology (QSP) to optimize drug discovery and companion diagnostics for liver diseases (NAFLD, Type 2 Diabetes and the liver as a metastatic niche for melanoma). The development of human, biomimetic microphysiology systems (MPS) are critical experimental models in the QSP programs. The vascularized liver MPS (vLAMPS) is the most recent contribution that creates continuous oxygen zonation, allows immune cell infiltration, limits the binding of hydrophobic molecules and permits the physical coupling of multiple organ MPS. vLAMPS is used in the liver disease studies listed above. He recently spun-off SpIntellx with other Pitt faculty that is a computational and systems pathology company that predicts optimal therapeutic strategies in solid tumors.
Molecular Mechanism of Heart Development:
Dr. Tsang has a long standing interest in dissecting the molecular mechanism of heart development and regeneration using the zebrafish as a model system. His lab is particularly interested in the role of the Ras/MAPK pathway in development, and recently they have focused on heart regeneration. Dr. Tsang is studying the role of Dual Specificity Phosphtase 6 (Dusp6) in this process. His current hypothesis is that Dusp6 function suppressed cardiac regeneration as zebrafish harboring mutations in Dusp6 show an accelerated regenerative response to injury. His lab uses both genetic and chemical approaches to elucidate how Dusp6 limits heart regeneration.
Ocular, Vascular, and Nerve Biomechanics, Tissue Engineering, Nonlinear Optical Micoscopy, and Finite Element Modeling:
Dr. Vande Geest is new to the University of Pittsburgh. While at the University of Arizona his lab initiated research in the area of vascular tissue engineering and developed perform functional in vitro and in vivo studies on a novel biopolymer vascular graft.
Inflammation; Computational Modeling; Systems Biology
Dr. Vodovotz leads an interdisciplinary effort combining computational, experimental, and clinical studies aimed at a systems-based understanding of inflammation. He has created novel, translational applications of mathematical modeling, including in silico clinical trials and patient-specific predictive models, culminating in the design of a biohybrid device for patient-specific, self-adaptive control of inflammation. He is a co-founder and current President of the Society for Complexity in Acute Illness and a co-founder of Immunetrics, Inc., a company that commercializes mathematical work in the context of the pharmaceutical industry, applying computational models of inflammatory disease in the rational design of new therapies.
Biomechanics and Regeneration of Tubular Tissues:
The overall goals of Dr. Vorp’s work are 1) to use optical and biomechanical interrogation techniques to evaluate changes in the structure and biomechanical properties that occur with diseases of tubular tissues (e.g., blood vessels, urethra, esophagus), and 2) to use regenerative medicine techniques to develop strategies for the repair or replacement of these tissues. Their tissue-engineered blood vessels (TEBV) are fabricated by seeding stem cells into a biodegradable, elastomeric supporting scaffold. They investigate the ability of the TEBV to remodel into a functional blood vessel. This includes exploring the fate of the seeded cells & translational logistics, such as scale-up, effect of age, gender & disease states (e.g., diabetes) on TEBV remodeling. They also explore the effects of physiologic biomechanical forces on mesenchymal stem cell differentiation & proliferation.
Biomaterials for Cardiovascular Tissue Engineering:
Dr. Wagner and his team work in the area of cardiovascular tissue engineering. This focus grew from the observation that much of the early work in this field relied upon scaffold material such as poly(lactic-co-glycolic acid), which does not mechanically mimic the properties of soft tissues such as those of blood vessels and the heart wall. The group has focused on the molecular design of thermoplastic biodegradable elastomers that would be amenable to control at both the synthetic and processing stages to achieve scaffolds optimized for a given application. The team, linking polymer chemists, bioengineers and surgeons, has synthesized, processed and characterized a wide variety of polymers and polymer based scaffolds for the replacement and augmentation of various tissue types. These materials have been characterized in vivo as replacement scaffolds for blood vessels and abdominal wall in addition to being used as a mechanical support material for the failing ischemic ventricle and vein grafts. Furthermore, the group has pioneered novel assays that allow the evaluation of circulating platelet activation in both bovine and ovine models. This work allows for a much greater insight to be obtained during cardiovascular device implantation to quantify improvements in device design (e.g. surface coatings and flow path refinement). We have also conducted a variety of clinical studies regarding platelet activation with disease and device implantation.
Bioengineering, Neural Coding, Neuroprosthetics, and Functional Electrical Stimulation:
Dr. Weber’s research focus is on neural engineering, including studies of functional electrical stimulation (FES), activity-based neuromotor rehabilitation, neural coding, and neural control of prosthetic devices. He has expertise in a range of advanced techniques for neurophysiology and biomechanics research, including 3D motion analysis, electromyography, multichannel neural recording and stimulation, human magnetoencephalography (MEG), human electrocorticography (ECoG). In addition, he has experience with a variety of animal models, including rat, cat, and non-human primates, as well as human subjects testing in laboratory and clinical studies. Active projects in his lab include development of motor and sensory neural interfaces for controlling and sensing prosthetic limbs. He is the founding Director of the Rehab Neural Engineering Laboratories (RNEL) here at the University of Pittsburgh. RNEL investigators work collaboratively on a range of projects aimed at the role of sensory feedback in supporting and regulating a wide range of perceptual, motor, cognitive, and autonomic functions.
Tissue Micro-Environment in Regeneration and Cancer:
Dr. Wells’ lab aims to understand how tissue microenvironment alters cell behaviors and phenotypes and how this regulation dictates physiologic and pathologic situations. They examine soluble and matrix signals. His lab also examines wound repair, primarily of the skin and bone especially focusing on stem cells that undergo a biphasic phenotype change during limited repair. In the pathological situation of tumor dissemination, the phenotypically transitioned carcinoma cells are phenotypically shifted to accomplish ectopic seeding, metastatic establishment and dormancy. To derive the molecular bases of these situations so as to rationally effect better outcomes, they investigate how integrated cell responses are selected and the metabolic and phenotypic consequences of such. This integrative approach has enabled them to employ cell and tissue engineering principles to design surfaces that specifically promote repair over scarring. They also pursue novel studies in tumor metastasis in an innovative liver bioreactor and in skin organ cultures ex vivo.
Wound healing, chemokine biology, matrix biology:
Studies in Dr. Yates’s laboratory are focused on dissecting the molecular and cellular mechanisms of skin remodeling and regeneration and its pathogenesis, by integrating basic science discoveries with clinical outcomes. Specifically, they are conducting animal and patient based research that incorporates multiple disciplines to accelerate discovery of novel treatment strategies for skin fibrosis in systemic sclerosis (SSc). The group is elucidating the biological mechanism that contributes to the coordination between inflammatory responses and extracellular matrix production that leads to development and progression of dermal fibrosis in SSc. In order to study fibrotic effects they use skin samples from patients with SSc, ex vivo organ cultures, and Y genetic animal models. Additional collaborative projects are in the areas of polymer based stem cell therapies for non-healing & scarring wounds and peptide therapies for pathological angiogenesis in eye diseases.
Liver Growth during Development, Restoration from Injury, Oncogenesis:
Dr. Yimlamai’s lab uses murine models to understand fundamental mechanisms of liver growth during development, its restoration from injury, and changes that lead to oncogenesis. They specialize in the Hippo Signaling Pathway, a relatively recently recognized signaling pathway that controls organ growth. Over the past 10 years, it has become well recognized that dysfunction of the Hippo pathway rapidly leads to an increase in organ size and eventually cancer. Currently, his group is focused on (1) how the Hippo pathway may be disrupted during chronic liver injury and if this leads to the development of liver fibrosis, and (2) defining novel regulators of the Hippo pathway. The short-term goal is to describe the pathophysiology resulting from dysregulation of the Hippo pathway in the liver and to identify clinically targetable pathways related to Hippo. The long-term goal is to develop a translational research program revolving around amelioration of liver disease and regeneration in children.
Tumor Immunology and Cancer Vaccines:
Hassane M. Zarour, MD, is a professor of Medicine, Immunology and Dermatology at the University of Pittsburgh School of Medicine. He is co-leader of the Melanoma Program and the Cancer Immunology and Immunotherapy Program. Dr. Zarour is board-certified in dermatology and cutaneous oncology. His research focuses on immunotherapies of melanoma and other solid tumors, T cell responses to tumor antigens and the mechanisms of tumor -induced T cell dysfunction. His work has led to the identification of multiple inhibitory pathways that cooperate with PD-1 to impede tumor antigen-specific T cell responses to melanoma and other solid tumors. His findings serve as a rationale for multiple first-in-human clinical trials with dual immune checkpoint blockade in cancer patients.
Adjunct Faculty Profiles:
Cardiopulmonary Organ Replacements:
Dr. Borovetz’s group applies state-of-the art bioengineering and tissue-engineering technologies towards the development of cardiopulmonary organ replacements for adult and pediatric patients. His experience in device development is invaluable for CATER students. He has multiple leadership roles in the Bioengineering department and CATER program.
3D culture, cell perfusion, bioreactors:
Dr. Gerlach is an expert in biohybrid liver development, bioreactor design for stem cell culture technologies, and skin cell therapy. His experience in building bioreactor systems is of immense interest to CATER trainees.
Wishwa Kapoor, PhD, MBA (General Internal Medicine)
The Institute for Clinical Research Education:
Dr. Kapoor is the Falk Professor of Medicine and Clinical and Translational Science, Chief, Division of General Internal Medicine, and Director, ICRE and Center for Research on Health Care. Dr. Kapoor is an internationally recognized expert in clinical and health services research focusing his efforts on clinical epidemiology and health services research, with studies on common medical problems such as syncope and community-acquired pneumonia. Over the past decade, he has also developed a major clinical research training enterprise at the University, the Institute for Clinical Research Education (ICRE). The ICRE provides multi-disciplinary, mentored training to emerging investigators at different stages in the career pipeline, from medical students to junior faculty. The ICRE offers an extensive array of graduate-level courses and formal degree-granting programs in clinical and translational science, including PhD, MS, and Certificate degrees. The ICRE also administers large-scale career development programs, including multiple institutional K12 & T32 awards, and programs for medical students and residents, all focused on clinical research.
Stem Cell, Lung and Liver Biology and Cancer:
Dr. Locker investigates the role of Nkx2.8, a developmental homeobox transcription factor, in stem cell proliferation in the lung, ventral brain, and ventral spinal cord. Nkx2.8 null mice get progressive changes in their large airways that eventually lead to cancer. The similarity to human lung cancer has led to a pilot study of Nkx2.8 as a tumor suppressor of human cancer. Their group also studies (1) transcriptional regulators that control liver development and cell proliferation, (2) long-distance transcription controls that regulate a chromosomal locus, and (3) regulation of gene expression through a specific control language. Ongoing research includes analysis of the domains of Nkx2.8, molecular reconstruction of enhancer-promoter interactions, chromatin structure, and combined molecular-bioinformatics analysis of gene control regions. A related project studies drugs and hormones that induce an alternate pathway of hepatocyte cell proliferation via nuclear receptor transcription factors. This form of proliferation is of particular interest because the drugs that activate it are powerful cancer promoters. Bioinformatics analysis of microarrays is a major part of the project—they are using arrays to define genes that activate the hepatocyte cell cycle and cause it to progress. Dr. Locker has extensive expertise in high throughput analysis including GWAS studies, CHIP-Seq and others.
Evan Facher, PhD, MBA (Technology Management)
The Innovation Institute:
Dr. Facher serves as the Vice Chancellor for Innovation and Entrepreneurship and Director of the Innovation Institute at the University of Pittsburgh. In this role, Evan promotes the commercial and societal potential of faculty and student discoveries, and works with regional businesses to enhance the Pittsburgh regional innovation ecosystem.
Wendy Mars, PhD (Pathology)
Cellular & Molecular Pathology graduate program:
Dr. Mars is the program director of Cellular & Molecular Pathology graduate program, course director of the Pathology seminar series and director of the committee overseeing annual Pathology retreat. She is part of the curriculum committee of the CATER program.
Dr. Oertel’s research evaluates cell transplantation strategies and identifies essential cell characteristics that relate to the repopulation of the liver and tissue microenvironment conditions that foster this repopulation. They discovered that fetal liver stem/progenitor cells sufficiently replace hepatic mass in the near-normal rat liver. Recent studies are examining mechanisms of enhanced cellular engraftment. The lab is also investigating the therapeutic potential of progenitor cell transplantation in treating hepatic fibrosis/cirrhosis.
Donna Beer Stolz, PhD (Cell Biology, McGowan Institute, and Pathology)
Center for Biologic Imaging:
Dr. Stolz is the associate director of the Center for Biologic Imaging and director of Electron Microscopy at the facility. She is instrumental in advising on imaging modalities for CATER trainee projects. She is also part of the CATER curriculum committee.
Biological Study of Development, Growth, Function and Health of Skeletal Tissue:
Dr. Tuan directs a multidisciplinary research program that focuses on orthopedic research as a study of the biological activities underlying the development, growth, function, and health of skeletal tissues, and the utilization of this knowledge to develop cell-based technologies that will regenerate and/or restore function to diseased and damaged skeletal tissues. Ongoing research projects are directed towards skeletal development, stem cells, growth factor signaling, bone-biomaterial interaction, extracellular matrix and cell-matrix interaction, nanotechnology, mechanobiology, regenerative medicine, & tissue engineering, utilizing integrated contemporary technologies of biochemistry, cell & molecular biology, embryology & development, cell imaging, & engineering.
Simon Watkins, PhD (McGowan Institute and Pathology)
Center for Biologic Imaging:
Dr. Watkins’ research as director of the Center for Biologic Imaging is focused on various aspects of the application of cutting edge microscopy in biomedical research. Overall his research tries to dissect molecular processes in the context of the living organism in 3D space in multiple colors over time at the highest speed and resolution possible. His support and leadership has been instrumental in providing a world-class imaging infrastructure to all CATER trainees.