Ed M. Greenfield, PhD (Director):
Dr. Greenfield’s research examines cellular mechanisms that regulate bone turnover in response to hormones, cytokines, orthopaedic wear particles, bacterial endotoxin, and osteosarcoma. His laboratory studies signal transduction, regulation of gene expression, and differentiation of osteoclasts and osteoblasts.
These studies use cell cultures as well as in vivo mouse models. The roles of specific molecules are studied using a variety of techniques, including gene knock out, gene knock down (siRNA and antisense), and neutralizing antibodies. These studies have important implications for regulation of bone turnover in various diseases, including osteoporosis, loosening of orthopaedic implants, and tumors.
Specific areas of current research include: the role of bacteria in “aseptic loosening” of orthopaedic implants, regulation of parathyroid hormone signaling by Protein Kinase Inhibitor, regulation of bone turnover by the gp130 family of cytokines, and mechanisms responsible for tumorigenesis and metastasis in osteosarcoma. Trainees can participate in all aspects of these projects and obtain diverse training in many aspects of modern bone cell biology.
Eben Alsberg, PhD:
Dr. Alsberg’s laboratory focuses on engineering functional biologic replacements to repair damaged tissues. One of the primary thrusts is on regeneration of musculoskeletal tissues. Complex signals that are implicated in musculoskeletal morphogenesis, repair, and homeostasis are used as a template for the development of biomaterials for tissue regeneration. Through the temporal and spatial presentation of bioactive factors, mechanical forces, and biomaterial physical and biochemical properties, microenvironments are created that regulate cell gene expression and new tissue formation.
Some areas of active investigation include controlling stem cell differentiation, delivering bioactive factors sequentially, developing spatially patterned constructs, understanding cell-cell interactions, and determining mechanical influences on cell function. Trainees can be involved in all parts of these investigations (e.g., biomaterials design, fabrication, and characterization, cell and molecular biology, in vitro and in vivo model systems, etc) to acquire strong research experience in musculoskeletal biomaterials development and tissue engineering.
Donald D. Anthony, MD, PhD:
Dr. Anthony is interested in defining the host immune phenotype associated with autoimmune manifestations of Hepatitis C (HCV) infection. The study of immunopathogenesis of autoimmune disease is greatly hampered by a lack of known autoantigens, and a lack of a known causal factor for these diseases. However, in the case of chronic viral infection, where the etiology is known, autoimmune manifestations can be common. HCV is the most common cause of chronic viral hepatitis in the United States, and is a significant cause of morbidity and mortality.
Evidence suggests that host immunity contributes to the pathogenesis of HCV mediated disease, participating in favorable outcomes and in organ damage. This same immune response has also been associated with autoimmune conditions, including thyroiditis, cryoglobulinemia, a high prevalence of autoantibodies, porphyria cutanea tarda, sicca syndrome, arthralgia, and membranoproliferative glomerulonephritis.
In order to understand how helpful (viral clearance) as compared to harmful (persistent hepatitis and autoimmunity) immune mediated outcomes occur during HCV infection, the immnopathogenic mechanisms involved must be evaluated in fine detail. An improved understanding of these issues is required to permit appropriate design of studies aimed at enhancing the anti-viral immune response and treating HCV infections.
Arnold I. Caplan, PhD:
Dr. Caplan is exploring the use of marrow-derived Mesenchymal Stem Cells for the repair or regeneration of musculoskeletal tissues. In many tissues, newly differentiated “replacement” cells are derived from multi-potent progenitors or adult stem cells. The cells responsible for the bone and skeletal repair are called Mesenchymal Stem Cells (MSCs) and these cells can give rise to bone, cartilage, muscle, marrow stroma (support for the Hematopoietic Stem Cell and its descendents), tendon/ligament, fat and other connective tissues.
The use of culture-expanded reparative cells for regenerative therapies requires delivery scaffolds and/or cytokine/growth factor treatments customized for each tissue and each site of repair. Dr. Caplan is developing reparative strategies, as well new technologies designed to enhance cell targeting and engraftment. Last, a new therapeutic approach, using MSCs to provide a trophic influence rather than cell-replacement, is being developed.
For use in ischemic injury to the brain or heart, MSCs appear to control the reparative micro-environment by inhibiting fibrotic scarring and enhancing angiogenesis. These trophic effects have profound implications on the use of MSCs for cell-based therapies.
Mark R. Chance, PhD:
Osteoarthritis (OA) is the most common musculoskeletal disorder, afflicting 40 million people in the United States alone. Our understanding of its pathophysiology and our ability to detect early disease is in its infancy. Our major focus is to develop and validate synovial fluid biomarker profiles for OA using advanced quantitative proteomics and mass spectrometry approaches.
In a pilot study with Dr. Gobezie, we have identified candidate biomarkers derived by analyzing the differential protein expression in multiple subjects among three populations: healthy controls, patients with early OA, and patients with late OA using proteomics and bioinformatics. The study resulted in a panel of candidate biomarkers that reveal fundamental patho-physiology of the disease. Ongoing work is attempting to understand the molecular pathways involved in progression of the disease.
Dwight T. Davy, PhD:
Dr. Davy’s research interests are in the biomechanical behavior of hard tissues and skeletal joints. These include the mechanics of bone, particularly the nonlinear behavior of bone, as well as reconstruction of skeletal systems, including fracture treatment and repair, and total joint reconstruction with bone grafts and graft substitutes. Recent focus has been on the measurement and modeling of the damage accumulation process in bone.
Current studies include the characterization of damage effects across loading modes (tensile damage effects on compressive, torsional properties, etc.), and in combined loading modes (tension+torsion, compression+torsion damage effects). Other studies have examined the modeling of damage evolution in cancellous bone and the characterization of anisotropic damage accumulation in cancellous bone. In addition, recent work has looked at damage accumulation and failure at extremely high loading rates.
Other work involves the incorporation of damage effects into the analysis of bone-implant systems and the inclusion of these effects in predicting fracture risk in diseased bone and in reconstructed skeletal systems.
David Dean, PhD:
Dr. Dean is an Associate Professor in, and Director of the Imaging Laboratory of, the Department of Neurological Surgery at Case Western Reserve University. Dr. Dean’s primary interest is the rapidly emerging field of Computer Assisted Surgery (CAS). CAS, especially for neurosurgery, requires the recognition of 3D structures within medical images to plan and provide stereotactic guidance for operatively administered therapy.
He has developed methods for the use of 3D CT images for the computer aided design (CAD) and 3D printing of patient-specific (i.e., custom), large-format, prosthetic implants. The accurate filling of the defect shortens surgery and improves outcome by protecting the underlying brain from trauma and infection. To date most custom, pre-operatively fabricated, large format, cranial implants received by patients have been produced from non-resorptive materials (e.g., polymethylmethacrylate or titanium).
It would be desirable to produce these implants from resorbing materials (i.e., tissue engineering). One of the keys to tissue engineering is to produce an artificial construct that fits the patient well and promotes its own incorporation through the ingrowth of adjacent bone tissue. Dr. Dean and his colleagues have patented a method that takes a CAD implant file and directly renders it in a resorptive polymer, poly(propylene fumarate) (PPF). Bone growth in these implants has been tested in athymic rat and dog models.
The strength and stiffness of these implants can be controlled by varying the PPF molecular weight and cross-linking density, respectively. Dr, Dean and his colleagues have also modeled the strength and stiffness of the skull using finite element analysis. The Imaging Laboratory’s goal in this research is the design of implants with patient-specific: external shape, material properties, and internal porosity.
James E. Dennis, PhD:
Dr. Dennis’ research is on tissue engineering of bone and cartilage. One project is focused on the characterization of cell surface molecules of bone marrow cells that correlate with bone formation, with the long-term goal of using these cells in clinical trials. Another project uses bioreactor systems to produce cartilage of sufficient thickness and biomechanical stiffness to be used as implants in animal models, and a related study looks at how growth factors and hypoxic conditions affect chondrocyte growth and differentiation.
Another project is centered around the development of methods to coat stem and progenitor cells with molecules that will direct those cells to sites where they can initiate repair. These targeting molecules contain a lipid moiety for membrane insertion, a spacer, and a cell- or matrix-binding motif. Trainees can become involved in various aspects of these projects as well as expanding these projects into related areas.
Steven J. Eppell, PhD:
Native type I collagen fibril gels will be self-assembled and mineralized under in-vitro conditions. The resulting gels will be doped with bioactive agents and pressed into shapes capable of load bearing. These samples will be analyzed physico-chemically, using in-vitro cell assays, and using critical-sized-defect small-animal models.
In a separate project, isolated collagen fibrils (both from sea cucumbers and from reconstituted gels) will be mechanically analyzed using a microelectromechanical system we have developed for this purpose. Strength and modulus of the individual submicron diameter fibrils will be measured. In a related project, the location of mineral within collagen fibrils will be measured using both atomic force microscopy and near field scanning optical microscopy.
Trainees will participate in all facets of these projects, including sample preparation and analysis, cell and animal experimentation, journal article preparation, and collaboration with surgeons currently working on the projects as well as with industrial partners.
Thomas A. Gerken, PhD:
Mucin-like domains are critical for proteoglycans involved in cartilage matrix formation where these domains serve as attachment sites for keratan sulfate (KS). The goal of this project is to characterize the regulation of the initial steps of mucin-type O-glycan biosynthesis. Kinetic modeling/simulation studies show that both peptide sequence and neighboring group glycosylation are important modulators of site specific O-glycosylation.
The peptide substrate specificities of the family of ppGalNAc transferases, which add GalNac to peptide substrates, and the Core 1, Core 3 and sialyl transferases, which add sugars to the peptide linked GalNAc, are currently under study. This will lead to the identification of isoform-specific substrates, the creation of isoform-specific inhibitors and the prediction of mucin-type O-glycosylation sites.
It has been shown that KS on cartilage aggrecan shows an age-dependent increase, and it has been suggested that this change may increase the degradation of aggrecan by aggrecanases. Trainees will participate in this work by characterizing the roles of the different ppGalNAc T isoforms in aggrecan glycosylation to determine whether the observed KS alterations with age are due to differential expression of these enzymes.
Reuben Gobezie, MD:
Dr. Gobezie’s research uses a systems biology approach to studying musculoskeletal disorders with a focus on mass spectrometry, protein microarrays, and other proteomics techniques as well as bioinformatics. The two major areas of research in his lab focus on arthritis and fracture healing.
Specifically, Dr. Gobezie’s group has identified the first highly predictive protein biomarkers for osteoarthritis (OA) by studying differential protein expression in synovial fluid from early and late OA against samples from healthy donors. His group is now validating the disease-specific performance of these biomarkers by studying synovial fluid from patients with rheumatoid arthritis. His laboratory is also analyzing plasma and urine to determine if the predictive value of these biomarkers is retained in these tissues.
His laboratory is also studying the proteome of fracture healing in a mouse model in order to understand the mechanism of the process of osseous union and non-union. Trainees can participate in all aspects of these projects and obtain diverse training in proteomics techniques and technologies that will be widely applicable to many scientific disciplines.
Victor M. Goldberg, MD:
Dr. Goldberg provides opportunities for trainees to participate in a number of basic research programs including investigations in bone and cartilage transplantation, new approaches to bone repair, and the exploration of new generations of prosthetic knee and hip joints. Dr. Goldberg’s laboratory is investigating the approaches to the use of cellular-based technology in the repair of full- and partial-thickness articular cartilage defects.
Studies have included investigations of bone and cartilage transplant with focus on experimental models evaluating the interplay of vascularization and immune response of the host. These projects are closely related to other projects by faculty sponsors and provide an opportunity for the trainee to participate in matrix molecular biology and cartilage repair technologies.
The basic concept continues to be the use of novel cellular constructs using mesenchymal stem cells as the basis for the repair of full- and partial-thickness defects of articular cartilage. New materials and interfaces are being explored with other investigators to develop new generations of prosthetic knee and hip joints with optimal design and interface characteristics. These areas of research allow close, active interactions among multiple faculty sponsors, providing an integrated experience for the individual trainee.
Christopher J. Hernandez, PhD:
Dr. Hernandez’s research concentrates on understanding bone biomechanical properties and how they are regulated by bone cell activity. Dr. Hernandez is presently approaching this problem with three research areas. The first is based on the hypothesis that the size and number of remodeling events within cancellous bone can influence whole bone mechanical properties independent of bone mass.
This project involves the development of new imaging techniques leading to three-dimensional dynamic bone histomorphometry. The second area is based on the hypothesis that bone remodeling targeted to regions of microdamage can have a much greater effect on cancellous bone mechanical properties than remodeling that is not targeted to regions of microdamage.
The third research goal is to understand the relationship between localized changes in cancellous bone structure and modifications in mechanical performance of whole bones, with special emphasis on the spine. Trainees may be involved in any of these projects and will gain expertise in in-vivo experimentation, biomechanics, and/or computational biomechanics.
Alex Huang, MD, PhD:
Regulation between immune activation and unresponsiveness is crucial in the pathogenesis of cancer, autoimmune disorders and infection. Historically, researchers have relied on investigative tools that involve teasing apart individual cells away from their native environment to study their function in a test tube, or obtaining static snapshots of where these cells migrate within the body through examination of fixed tissues under the microscope. While useful tools in uncovering many of the principle processes which govern how cells communicate with one another, these traditional investigative tools cannot fully reconstitute the myriad of environmental cues which the immune cells gather and interpret for their proper function. Through advances in 2-photon microscopy technology, we are now able to visualize how immune cells interact with their neighbors and pathogens in their native environment in real time with single-cell resolution. Our laboratory is interested in applying this and other classical immunological techniques to directly visualize aspects of cellular migration, homing, and interaction in animal models of disease such as cancer and multiple sclerosis. Ongoing projects include: 1) Testing the efficacy of genetically-modified tumor vaccines in the setting of sarcomas (osteosarcoma; rhabdomyosarcoma) and other childhood cancer; 2) Investigating factors which influence the dynamic recruitment of T cells and their interactions within tumor microenvironment; 3) Studying mechanisms of immune surveillance in micro-metastasis of osteosarcoma; 4) Interrogating molecular signaling crosstalk in immune cells; 5) Imaging dynamic interaction between the brain tissue and pathogenic cells that causes an animal model of multiple sclerosis; 6) Developing imaging techniques to interrogate immune cell migration and interactions in tissues such as the bone marrow, lung, kidney, GI tract and the skin.
The long-term goal of our laboratory is to translate insights gained from basic investigations of in vivo immunity into rationally designed tumor vaccine and immunotherapeutic clinical trials, with a particular emphasis in the areas of pediatric sarcomas and other solid tumors.
Robert F. Kirsch, PhD:
Dr. Kirsch’s research focuses on restoring movement to disabled individuals using functional electrical stimulation (FES) and controlling FES actions via natural neural commands. Computer-based mechanical models of the human upper extremity are used to develop new FES approaches. FES user interfaces, including those based on brain recordings, are being developed to provide FES users with the ability to command movements of their own arm.
Feedforward and feedback control strategies that improve performance while reducing the cognitive burden on the user are under development. Several advanced upper extremity neuroprostheses have been surgically implanted in paralyzed individuals and are undergoing functional evaluations. Collaborations with commercial partners are being pursued to facilitate the deployment of FES technologies into clinical practice.
Zhenghong Lee, PhD:
Specific imaging modalities such as CT or SPECT, or PET allow Dr. Lee to study the subject repeatedly, non-invasively, and quantitatively. Among these imaging modalities, uCT stands out as a well-developed tool for use in bone studies. Specialized measurements of bone parameters or characterizations can be made from the acquired CT image data. SPECT, PET, and Bioluminescent Imaging (BLI) can be used to trace infused cells’ (including stem cells) distribution, dynamics, and differentiation, and to measure gene expression, protein-protein interactions, and signaling pathways.
PET and SPECT data will be used for more quantitative measurement, but BLI will be used for screening or daily monitoring due to its high sensitivity in terms of the number of the cells it can detect and the amount of gene expressed that can be imaged. BLI requires no radioactive materials, allowing easy use in various lab settings.
Overall, these imaging techniques offer non-traditional ways to study biology, which may help trainees who are only familiar with regular bench type lab work. Depending on the nature of the research project as well as the interest and willingness of a trainee to go “outside the box”, imaging-based research provides a new approach to study old and new problems. This should benefit the trainee as well as the research program as a whole.
Paul N. MacDonald, PhD:
Vitamin D (Vit D) is required for normal calcium and phosphorus homeostasis and it is essential for the proper development and maintenance of bone. Vit D also exerts profound effects on cell proliferation and differentiation, inhibiting the proliferation of many malignant cell lines.
The vitamin D endocrine system also profoundly influences normal keratinocyte function and is protective against chemically induced skin tumorigenesis. The mechanisms underlying its tumor protective and anti-proliferative roles are currently unknown. The biological effects of Vit D are mediated through a nuclear protein termed the vitamin D receptor, or VDR. The VDR is a member of the superfamily of nuclear receptors that function as ligand-activated transcription factors.
Thus, Vit D and VDR together regulate the expression of specific genes or gene networks in classic target organs such as the intestine, bone, and skin. The global objective of Dr. MacDonald’s laboratory is to understand the molecular details and signaling mechanisms involved in VDR-mediated gene expression. We are currently focusing on in vivo and in vitro models of bone and skin to understand the gene networks that are involved in Vit D effects on bone development and skin tumorigenesis.
Charles J. Malemud, PhD:
Dr. Malemud’s research focuses on the role that apoptosis plays in the pathogenesis and progression of several arthritic conditions and autoimmune disorders. Interleukin-1 (IL-1), tumor necrosis factor- (TNF-), and nitric oxide (NO) levels are significantly elevated in degenerative joint diseases. IL-1, TNF-, and NO induce human chondrocyte apoptosis in vitro, and apoptosis frequency is often elevated in aging or osteoarthritic cartilage.
Joseph M. Mansour, PhD:
Dr. Mansour’s research concerns the mechanical behavior of soft tissues, focusing primarily on tissue engineered, osteoarthritic and native cartilage. Material properties are evaluated using indentation and unconfined compression. Indentation is often used since it is particularly well-suited for evaluating properties of cartilage from small experimental animals such as rabbit, which is often used in osteoarthritis and cartilage tissue engineering research.
The recently demonstrated ability to grow relatively large (centimeter sized) sheets of cartilage in the Skeletal Research Center has opened new opportunities for trainees to develop and implement a broader range of evaluation procedures than have been used in the past. These include tribological studies, evaluation of tissue adhesives, and developing relationships between the tissue’s mechanical and biological behavior.
In addition to measuring material properties, we have developed methods to evaluate changes in knee kinematics in rabbit OA models. Testing procedures based on reduction of strength due to repeated loading are also used.
Randall E. Marcus, MD:
Dr. Marcus is actively involved in a broad spectrum of research within Orthopaedics as the Department Chairman. His involvement ranges from intramedullary nail design to DNA repair in aging stem cells. His primary research interests are in surgical blood conservation and the design of implants for fracture fixation.
Trainees would have the opportunity to become involved in research on the use of recombinant DNA technology for the treatment of surgical anemia. This funded research program has resulted in numerous publications in peer-reviewed journals. Dr. Marcus, in conjunction with biomedical engineers, has also been successful in translational research in the area of implant design for fracture fixation.
He has developed an international reputation in the area of biomechanics as pertains to fracture fixation and has had fellows over the last 10 years who have been funded to study with him at Case. Trainees would have the opportunity to participate in this research, which is primarily focused on intramedullary fixation devices.
Finally, Dr. Marcus’ clinical research is focused on techniques in foot and ankle reconstructive surgery and trauma. Trainees over the last decade have participated in numerous studies in each of Dr. Marcus’ research areas that have resulted in peer-reviewed publications.
Shunichi Murakami, MD, PhD:
Dr. Murakami’s laboratory focuses on the role of Fibroblast growth factor (FGF) and Mitogen-activated Protein Kinase (MAPK) signaling in mesenchymal cells. During embryonic development, FGFR2 is expressed in the perichondrium and periosteum in the long bones, mesenchymal cells in the cranial sutures, and osteoblasts. Activating mutations in FGFR2 cause skeletal syndromes characterized by craniosynostosis.
These include Apert and Crouzon syndromes. In contrast, FGFR3 is expressed in proliferating and prehypertrophic chondrocytes in the growth plates. Activating mutations in FGFR3 cause the most common forms of human dwarfism, achondroplasia and thanatophoric dysplasias, indicating FGFR3 is a negative regulator of bone growth. Dr. Murakami hypothesizes that the MAPK pathway plays an important role in FGFR2 and FGFR3 signaling during skeletal development.
He uses genetically engineered mice to identify the role of MAPK and FGFR in skeletal development. His recent genetic experiments strongly suggested that Fgfr3 signaling inhibits bone growth by inhibiting hypertrophic chondrocyte differentiation through the MAPK pathway. Recent experiments also indicated that Fgfr3 and the MAPK pathway control the timing of growth plate closure.
Dr. Murakami’s current research focuses on the mechanisms whereby Fgfr3 and the MAPK pathway control chondrocyte differentiation and closure of the growth plates. To gain further insights into the roles of the MAPK pathway in skeletal development, he is inactivating MAPK in FGFR2 and FGFR3-expressing tissues using the Cre-loxP system. The trainees will be involved in the generation and analysis of genetically engineered mice and molecular and cellular experiments to identify the roles of the MAPK pathway in skeletal development.
P. Hunter Peckham, PhD:
Dr. Peckham’s research is in rehabilitation engineering and neural prostheses. Research focuses on functional restoration of the paralyzed extremities in individuals with spinal cord injury. Dr. Peckham has developed implantable neural prostheses that utilize electrical stimulation to control neuromuscular activation and provide control of grasp-release in individuals with tetraplegia.
This function enables individuals with central nervous system disability to regain the ability to perform essential activities of daily living. Dr. Peckham’s efforts concern the integration of rehabilitation and surgical approaches to restore functional capabilities. He is working on an advanced neuroprosthesis that employs implantable sensors for internal control and regulation of movement.
Clare M. Rimnac, PhD:
Dr. Rimnac’s research encompasses orthopaedic implant retrieval analysis and mechanical behavior of polymeric biomaterials and hard tissue. The mechanical behavior of polymeric biomaterials research has been directed towards the mechanical and clinical performance of ultra high molecular weight polyethylenes (non-crosslinked and crosslinked) used in orthopaedic total joint replacements and poly(propylene fumarate) used in the manufacture of bioresorbable scaffolds for hard tissue regeneration and repair.
There is an overall emphasis on understanding in-vivo failure mechanisms and on methods of improving the long-term performance of these implant materials. Current research efforts include: constitutive modeling of UHMWPEs and PEEK materials used in total joint replacements; and design, manufacture, and validation of craniofacial three-dimensional scaffolds for repair of large structural bone defects using poly(propylene fumarate).
The implant retrieval analysis research involves failure and damage analysis of implants removed at revision surgery to determine the cause of failure and the mechanisms responsible for the damage, and the application of results in design analyses to improve the performance of implant designs under development.
The research on mechanical properties of hard tissue has been focused on examination of the contribution of damage accumulation, at the ultrastructural and microstructural levels, to the increase of skeletal fragility (particularly static and cyclic crack growth resistance) with age.
Ronald J. Triolo, PhD:
Dr. Triolo’s research encompasses rehabilitation engineering, biomechanics, control of posture and balance, bipedal gait analysis, and seated ergonomics. He investigates applications of functional electrical stimulation (FES) for exercise, standing, walking, and trunk control in paralyzed patients.
Projects include:
1) clinical evaluation of implanted neuroprostheses for standing;
2) automatic control of standing and seated balance;
3) ambulation after incomplete spinal cord injury;
4) seated posture, reach, and wheelchair function;
5) selective neural interfaces.
Basic aspects of his research focus on the biomechanics of human movement, dynamic modeling of the musculoskeletal system, and advanced control systems for regulating posture with FES. These projects have developed a three-dimensional computer model of human stance that includes the pelvis, bones, joints, and muscles of both lower extremities, as well as a realistic model of the kinematics of the spine and the moment generating capacities of the major trunk muscles.
His recent R01 focuses on the design, optimization and clinical testing of stimulating nerve cuff electrodes for fascicular selectivity in mixed peripheral nerve trunks. Dr. Triolo also directs the Case/VA Advanced Platform Technology Center which designs new assistive technologies and medical devices.
Horst A. von Recum, PhD:
Dr. von Recum’s research is in Drug Delivery and in Tissue Engineering. The drug delivery group focuses on the use of molecular interactions to control the rate of release of therapeutic molecules several orders of magnitude longer than is possible by conventional diffusion based drug delivery.
Applications of this research are in delivery of antibiotics from implants, which are bioavailable locally from weeks to months. This is particularly relevant in orthopedic applications in which implants may become colonized with bacteria up to a year after implantation.
This same technology is being investigated to reversible associate biological molecules such as attachment peptides and growth factor molecules on the surface of an implant. The Tissue Engineering group focuses on the directed differentiation of embryonic stem cells into endothelial cells or endothelial precursors for formation of a vascular bed.
Guang Zhou, PhD:
Dr. Zhou’s laboratory focuses on studying how transcription factors interact with each other to determine cell fate and regulate cell function during skeletogenesis and bone metastasis. Utilizing molecular, biochemical, and genetic approaches, Dr. Zhou has shown that chondrogenic transcription factor SOX9 is a strong inhibitor for osteogenic transcription factor RUNX2 during bone formation.
His laboratory is currently studying the role of SOX9 in chondrocyte hypertrophy, bone mechanical strength, bone marrow stromal cell differentiation, and osteoarthritis pathogenesis using transgenic mice. His laboratory has also recently demonstrated that an evolutionarily conserved transcriptional cofactor, Jab1, plays essential roles in successive steps of skeletogenesis in vivo.
Other projects in Dr. Zhou’s lab include studying the roles of tumor suppressor genes Rb and p53 in chondrocyte and osteoblast differentiation and bone tumorigenesis using transgenic and knockout mice models. Dr. Zhou’s work will provide a better understanding of how tissue-specific and ubiquitous transcription factors interact with each other to control bone and cartilage formation.
Eventually, this work could lead to the development of therapeutic and diagnostic methods for bone diseases. Trainees can participate in all aspects of these projects and obtain comprehensive training in various aspects of bone and cartilage biology with emphasis on mouse genetics and cell biology.