Compendium of Stem Cell Researchers at UMDNJ & Rutgers
Rutgers University Faculty:
Martin Grumet, Ph.D.
Professor, Department of Cell Biology and Neuroscience
Director, W.M. Keck Center for Collaborative Neuroscience
Rutgers Stem Cell Research Center
Modulation of recovery from neural trauma by neural stem cells
Neural stem cells give rise to neurons and glia during development providing most of the cells that form the nervous system but very few stem cells persist in the adult brain. Transplantation of neural stem and progenitor cells into the injured central nervous system is a promising approach to promote repair and recovery after injury. Towards that goal, we are analyzing the development of different kinds of neural cells that can be derived from embryonic stem (ES) cells in the laboratory and testing their behavior after transplantation into the injured nervous system.
Ronald P. Hart, Ph.D.
Professor, Department of Cell Biology and Neuroscience
W.M. Keck Center for Collaborative Neuroscience
Rutgers Stem Cell Research Center
Regulation of microRNA gene expression in differentiating neural stem cells
The key to transforming human stem cells into therapeutic transplants is the faithful control of differentiation – the process by which cells acquire specialized functions during embryogenesis – in the culture dish. A newly-discovered class of regulatory molecules, known as microRNAs, has been discovered to be required for stem cell differentiation. Our experiments will help to define groups of microRNAs that are regulated during neurogenesis and how they work to control production of neurons or
non-neuronal cells in the nervous system. We propose that addition of artificial microRNA molecules will help control differentiation of stem cells prior to transplant, helping to guide the differentiation process towards cell types that are desired and away from products that are unwanted, and enhancing the utility and safety of therapeutic stem cells.
Melitta Schachner, Ph.D.
Research Professor II
New Jersey Professor of Spinal Cord Research
W.M. Keck Center for Collaborative Neuroscience
Department of Cell Biology and Neuroscience
Therapeutic use of genetically engineered human ES cells overexpressing the neural cell adhesion molecule L1
My research focuses on recognition molecules found on or near the surface of nerve cells. These molecules tell cells whether they can bind together, an activity important in repairing damaged nervous system tissue. The neural cell adhesion molecule L1 regulates brain development by promoting contacts between nerve cells, thus generating a functional nervous system. Its beneficial influence is important for regeneration after trauma, for example, in spinal cord injury or Huntington's and Parkinson's diseases. When overexpressed in mouse ES cells, L1 enhances survival of imperiled host nerve cells, makes the overexpressing stem cells migrate better in the host tissue, and helps form connections between the transplanted stem cells and the host leading to functional recovery. Important also is its ability to halt tumor formation. We are working toward developing human ES cell lines which overexpress L1, monitor their beneficial potential, and expand their therapeutic potential.
Jay A. Tischfield, Ph.D., FACMG
Duncan and Nancy MacMillan Prof of Genetics & Chair
(Prof of Pediatrics and Psychiatry, Robert Wood Johnson Medical School, UMDNJ)
Rutgers University Cell and DNA Repository
Genetic and Structural Analysis of Mouse ES Cells and their Derivatives
Because of their unique role as progenitors of the entire organism it is particularly important that ES cells maintain genetic stability so that successive generations of individuals are healthy. It is also critical that ES cells that may be used for therapy maintain this stability with continuous culture outside of the body. We have noted lower rates of mutation and loss of genetic variation in mouse ES cells compared to mouse adult body cells. We are investigating the mechanisms responsible for this genetic stability at the levels of DNA repair and cell death, using a combination of genetics and cell biology techniques.
Changshun Shao, Ph.D.
Assistant Research Professor
Department of Genetics
Stem cell origin of spontaneous and radiation-induced mutations recovered in T cells
Our research is focused on the role of genetic changes in cancer development. While genetic changes, or mutations, may arise in any type of cells, probably only those mutations in stem cells can initiate and drive cancer development. Using mouse models, we are trying to determine the exact development stage at which mutations emerge during blood cell formation, and to determine whether blood stem cells are more (or less) susceptible to acquisition of mutations than one type of differentiated cells. Information generated from this research is important to understand cancer development and to develop more effective therapies against cancer.
Prabhas V. Moghe, Ph.D.
Professor, Department of Biomedical Engineering
Department of Chemical & Biochemical Engineering
Advances in biomaterials and nanotechnology to control
stemness vs. differentiation of stem cells
Human stem cells hold great potential to be a source of regenerative tissues and organs, but technical barriers limit the ability of such cells to differentiate into specialized cells, especially in three-dimensional systems and on synthetic materials, and to expand rapidly without losing their 'stemness'. The Moghe laboratory and collaborators are integrating nanotechnology within 3-dimensional biomaterial systems -- the nanoscale biological features of such scaffolds can interact with stem cells and be used as a basis to more precisely trigger accelerated differentiation. Additionally, the Moghe laboratory and collaborators are developing a high content imaging based tool box to screen stem cells on synthetic biomaterials -- this profiling strategy could be used to identify the materials that most rapidly push stem cells toward desired types of endpoints or lineages and away from undesired endpoints.
University of Medicine and Dentistry of New Jersey
Debabrata Banerjee, Ph.D.
UMDNJ-RWJMS, Associate Professor, Depts of Med/Pharmacology
Gene delivery to tumor cells has been a challenging problem in experimental therapeutics. Various methods for gene delivery to tumors have been explored, including cellular methods. Mesenchymal stem cells (MSCs), which give rise to bone cells, fat cells, etc., appear to be good candidates for tumor targeting as they have been shown to “home” to sites of injury and to tumors when administered systemically. Although MSCs have been demonstrated to migrate to in vivo sites including bone marrow, tumor microenvironment and sites of injury and inflammation, the molecular basis of migration remains to be clarified. In order for MSCs to become effective cellular delivery vehicles for tumor therapy, improved understanding of the molecular mechanisms involved in migration of MSCs to tumor sites is necessary. Dr. Banerjee and his colleague, Dr. John Glod, study the molecular mechanisms involved in this process with the aim of designing strategies for improving targeting of human MSCs to tumor sites for therapeutic purposes. This work has been supported by the New Jersey Department of Treasury and the New Jersey Commission on Cancer Research.
Joseph Bertino, M.D.
UMDNJ-RWJMS University Professor, Depts of Medicine/Pharmacology
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Dr. Bertino is Interim Director of the Stem Cell Institute of New Jersey is also Interim Director of the Cancer Institute of New Jersey in New Brunswick. In addition, Dr. Bertino is an American Cancer Society professor and is internationally recognized for his role in finding curative treatments for leukemia and lymphoma. Dr. Bertino’s laboratory studies the relationship between tumor suppressor gene abnormalities and drug resistance and the use of drug resistant genes to protect bone marrow from chemotherapy toxicity. His laboratory is also interested in the transfer of drug resistance genes into hematopoietic stem cells.
Dr. Bertino recently won a $250,000 grant from the New Jersey Department of Treasury and the New Jersey Commission on Science and Technology to investigate expanding umbilical cord blood (UCB) stem cells ex vivo (i.e. outside the body). If successful, Dr. Bertino’s work could lead to a method to provide sufficient numbers of stem cells that can be used in bone marrow transplantation in patients with advanced hematologic malignancies who do not have alternate donor choices.
Patricia Fitzgerald Bocarsly
UMDNJ-NJMS, Professor, Dept of Pathology/Laboratory
In Dr. Fitzgerald-Bocarsly's laboratory, studies on the innate immune
response to viral infection are focused on plasmacytoid dendritic cells
that produce large quantities of interferon-alpha in response to viral
stimulation. Mechanisms of viral induction of interferon in these
cells, their differentiation from bone marrow precursors and their
potential role in cancer and HIV immunotherapy are under investigation.
Tulin Budak-Alpdogan, M.D.
UMDNJ-RWJMS Assistant Professor, Dept of Medicine
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Dr. Tulin Budak-Alpdogan and The Cancer Institute of New Jersey (CINJ ) won a $300,000 for “Post-Transplant High-Dose MTX/ARA-c Consolidation: A Drug Resistance Gene Transfer” from the NJCST in 2007. This pilot study will transfer a group of novel drug resistance genes into the stem cells of cancer patients for myeloprotection and better chemotherapeutic drug tolerance. This will be the first clinical study that will evaluate both the therapeutic benefits of dose-escalating post-transplant treatment and the safety of the gene transfer technology.
Dr. Alpdogan is also managing the new GMP (Good Manufacturing Practices) Facility of the Stem Cell Institute of New Jersey. This Facility is designed for the production of cellular and biological products. The Facility, located in the Cancer Institute of NJ, has 4 “clean” rooms for cellular product manufacturing, vector production, and a separate translational research laboratory for research and development. The scientists and technical staff associated with the Facility will work to optimize the conditions and techniques for making clinical protocols a reality.
Patrizia Casaccia-Bonnefil, M.D.
UMDNJ-RWJMS Assistant Professor, Dept of Neuroscience & Cell Biol
Dr. Patrizia Casaccia-Bonnefil’s research centers on understanding cell proliferation and differentiation in the central nervous system. She recently received a $2,518,857 from the NJCST for “ Bioengineering Human Embryonic Stem Cells.” This grant will support four integrated research projects and Core Facilities which will combine cell biology, state-of-the art imaging, gene transfer and genomics to facilitate progress in human embryonic stem cell (hES) gene transfer, differentiation and epigenetics studies. The Core will support research projects to engineer hES cells for controlled differentiation and targeted migration of myelin forming cells. The overall goal is to provide a platform that will allow scientists in different disciplines to develop differentiation protocols for obtaining multiple cell types, including hematopoietic, osteogenic, and myocardial cells for the recovery of function in a wide variety of disorders. This project is truly collaborative and involves a large group of co-investigators, including Dr. Monica Roth (Dept of Biochemistry, RWJMS), Dr. Randall McKinnon (Dept of Surgery, RWJMS), Dr. Vincenzo Pirrotta (Dept of Cell Biology, Rutgers University), and Dr. Richard Scott (IVF Clinic RMA in Morristown). In addition, Dr. Zui Pan (Dept of Physiology, RWJMS) will be the Director of the Imaging Facility.
Rick Cohen, Ph.D.
Assistant Research Professor/Director Stem Cell Resource Center
Dr. Cohen studies mechanisms that govern the transition of a multipotent stem cell into a differentiated cell. In 2007, he received $300,000 in funding from the NJ Commission on Science and Technology for the Center for Applied Training in Human Embryonic Stem Cell Biology to provide basic and advanced training in the field of human embryonic stem cell biology and to develop a well-trained pool of scientists in New Jersey proficient in human Embryonic Stem Cell culture techniques with the goal of advancing New Jersey’s leadership in stem cell research.
Emanuel di Cicco Bloom, M.D.
UMDNJ-RWJMS, Professor, Dept of Neurosciences & Cell Biology
Dr. di Cicco Bloom studies the basic processes that may underlie autism, schizophrenia and other developmental brain disorders.
Cheryl Dreyfus, Ph.D.
UMDNJ-RWJMS, Professor & Acting Chair, Dept of Neuroscience
The Dreyfus laboratory examines potential therapeutic approaches to the demyelinating disease, Multiple Sclerosis and the degenerative disease, Alzheimer’s Disease. In both of these devastating conditions, oligodendrocytes, the cells that provide an insulating sheath to neurons and enhance neuronal function, die. The laboratory’s goal is to enhance the regeneration of oligodendrocytes by increasing the survival, proliferation and differentiation of oligodendrocyte stem cells that live in the adult brain. They focus on identification of molecules and signaling pathways that are responsible for this regenerative process.
Ronald Ellis, Ph.D.
UMDNJ-SOM, Associate Professor, Dept. of Mol Biol
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In the germ line, a population of stem cells divides repeatedly to produce the cells that will become sperm or eggs. Dr. Ellis studies how the genes that regulate sexual identity influence cell proliferation. In some situations, mutations that transform male germ cells into female ones cause abnormal proliferation and tumors.
UMDNJ-NJMS, Assistant Professor, Dept of Cell Biol & Mol Medicine
The focus of Dr. Fraidenraich’s lab is to design paradigms for embryonic stem cell (ESC) based repair of cardiac and skeletal muscle defects using mouse models of human disease. Dr. Fraidenraich’s lab injects ESCs into mutant blastocysts, which are early embryos predisposed to develop disease. This unique procedure allows ESCs to find a natural environment where they can gradually differentiate and ultimately prevent disease from occurring. Using the tools of microarray and proteomic analysis on healthy and disease susceptible specimens, and comparing experimental with biomedical databases, the ultimate aim is to identify cardiotrophic and myotrophic factors effective for regenerative therapy of congenital disease. Dr. Fraidenraich’s work is funded by the NIH, the American Heart Association and the New Jersey Commission on Science and Technology.
UMDNJ-SOM, Dept of Cell Biology
Mecide Gharibo, M.D.
UMDNJ-RWJMS Assistant Professor, Dept of Medicine
firstname.lastname@example.org (cc: email@example.com)
Dr. Gharibo’s research interests are in leukemia, lymphoma, and other hematologic malignancies. Dr. Gharibo is a member of the Stem Cell Transplantation Group, where physicians actively perform stem cell transplants on a variety of illnesses where this treatment is indicated. These include acute and chronic leukemia’s, myelodysplasia, lymphomas both low and high-grade, chronic lymphocytic leukemia, Hodgkin’s disease and myeloma. Both autologous and allogeneic transplants are performed. The sources of transplant include matched siblings as well as matched unrelated donors from the National Marrow Donor Program. The program also performs cord blood transplants.
Gregg Giannina, M.D.
UMDNJ-RWJMS Assistant Professor, OB/GYN
Dr. Giannina’s research focuses on fetal surgery, prenatal diagnosis, fetal therapy and clinical perinatology. Dr. Ginannina is a member of the Fetal Wellness Center, whose mission is to provide the most comprehensive, state-of-the-art fetal evaluation and therapy services in the state of New Jersey and in the country. The three main elements of the mission are high-quality care, research and education. The center also carries out a variety of fetal procedures, including targeted sonography to assess fetal anomalies, non-stress tests, biophysical profiles, Doppler velocimetry, fetal echocardiography, percutaneous umbilical blood samplings, chorionic villus samplings, amniocentesis, fetal surgery and first trimester nuchal translucency combined screening. The Fetal Wellness Center provides human tissue for stem cell resource center.
John Glod, M.D.
UMDNJ-RWJMS Assistant Professor, Pediatric Hem/Onc
firstname.lastname@example.org (cc: email@example.com)
Gene delivery to tumor cells has been a challenging problem in experimental therapeutics. Various methods for gene delivery to tumors have been explored, including cellular methods. Mesenchymal stem cells (MSCs), which give rise to bone cells, fat cells, etc., appear to be good candidates for tumor targeting as they have been shown to “home” to sites of injury and to tumors when administered systemically. Although MSCs have been demonstrated to migrate to in vivo sites including bone marrow, tumor microenvironment and sites of injury and inflammation, the molecular basis of migration remains to be clarified. In order for MSCs to become effective cellular delivery vehicles for tumor therapy, improved understanding of the molecular mechanisms involved in migration of MSCs to tumor sites is necessary. Dr. Glod and his colleague, Dr. Banerjee, study the molecular mechanisms involved in this process with the aim of designing strategies for improving targeting of human MSCs to tumor sites for therapeutic purposes. This work has been supported by the New Jersey Department of Treasury and the New Jersey Commission on Cancer Research.
Nancy Hayes, Ph.D.
UMDNJ-RWJMS Associate Professor,
Dr. Hayes research focuses on the genetic regulation of cell proliferation in the developing and adult CNS of normal and mutant mice.
Hristo Houbaviy, Ph.D.
Dr. Houbaviy was recently awarded an NJCST grant for $300,000 to study MicroRNAs MiR-290-295 in Blastocyst-Derived Stem Cells and the Early Mouse Embryo. This study aims to understand stem cell development and lineage determination with the goal of expanding and improving knowledge of areas of stem cell biology currently not well understood.
Sergei Kotenko, Ph.D.
UMDNJ-NJMS, Associate Professor, Dept of Biochem & Mol Biol firstname.lastname@example.org
Dr. Kotenko studies how cytokines might be used in new ways to direct the immune response to control cancers, viral infections and inflammatory diseases. In particular, he’s looking at the stem cells in the bone marrow and how these bone, cartilage, fat and connective tissue precursor cells are affected by exposure to specific pathogens and also how these affected stem cells respond to cytokines.
John Langenfeld, M.D.
UMDNJ-RWJMS, Assistant Professor, Dept. of Surgery
Dr. John Langenfeld was awarded $300,000 in 2007 from the NJCST for “Identification of Tumor Stem Cells in Lung Cancer.” This proposal will identify and provide a better understanding of the biology of lung cancer cells that behave like stem cells. These data are likely to lead to new therapeutic strategies for the treatment of lung cancer.
Paola Leone, Ph.D.
UMDNJ-SOM, Associate Professor, Dept of Cell Biology
Director, Center for Cell & Gene Therapy
Dr. Leone's research is focused on the development and use of human
fetal neural stem cells for in vivo repair of the white matter component
of the central nervous system for the treatment of Canavan disease and
other white matter disorders/injuries. Her research interests have included in vivo neurochemistry of epilepsy and gene transfer approaches for the treatment of neurological disorders. She has published extensively in the field of CNS gene therapy and conducted the first direct gene therapy trial using a liposome-based vector for a pediatric neurodegenerative disorder. In addition to applications of viral vectors and stem cells, Dr. Leone is studying pharmacological approaches in humans and in animal models of Canavan Disease, Amyotrophic Lateral Sclerosis, Tay Sach’s and other neurological disorders.
Steven Levison, Ph.D.
UMDNJ-RWJMS, Professor, Dept of Neurosciences & Neurology
The overall goal of Dr. Levison’s research program is to better understand the signals that regulate the proliferation and differentiation of the somatic stem cells of the central nervous system. Stem cells of particular interest to Dr. Levison reside within a geographically restricted region of the brain known as the subventricular zone (SVZ). Ongoing studies in his lab are investigating the capacity of these neural stem cells to repair the brain after injury and how families of polypeptide growth factors (e.g. epidermal growth factor (EGF), insulin-like growth factor (IGF) and fibroblast growth factor (FGF)) act singly or in combination to affect the expansion of the neural stem/progenitors of the newborn brain. Dr. Levison’s laboratory is focused on understanding how regeneration of the CNS can be influenced by activating resident neural stem cells within the subventricular zone. Additional efforts are directed towards gain a broader understanding of how proliferation of stem cells may become dysregulated (i.e. as a consequence of injuries) leading to the formation of brain tumors. Dr. Levison’s laboratory uses a variety of animal models of neurological diseases, as well as cell culture systems for rodent neural stem cells. It is anticipated that future studies will be performed on human neural precursors.
Shaohua Li, M.D.
UMDNJ-RWJMS, Assistant Professor, Dept of Path & Lab Medicine
Basement membranes are evolutionarily ancient cell-associated extracellular matrices (ECMs) that are required for embryonic development and for normal tissue functions. They are found under epithelial layers, around the endothelium of blood vessels, and surround muscle, peripheral nerve, and fat cells. Mutations affecting the laminin, collagen, and proteoglycan components of these ECMs cause diseases of muscle, kidney, nerve, brain and skin. Dr. Li is part of the Matrix Biology Laboratory, the goals of which are to understand how different basement membranes assemble and influence cell behavior and how this process regulates embryonic differentiation. In 2007, Dr. Li was awarded $298,246 from the NJCST for “Vasculogenesis from Embryonic Stem Cells.” This research will study the integrin signaling pathway that directs the formation of primitive vascular tissues from multipotential embryonic stem cells.
Randall McKinnon, Ph.D.
UMDNJ-RWJMS Associate Professor, Depts of Surgery/Pharmacology
Myelin, the insulating sheath that protects neuronal axons, is destroyed in diseases such as multiple sclerosis and after spinal cord injury. Stem cells hold great promise as a source of replacement cells to repair the damage. Dr. McKinnon’s studies focus on deriving patient-specific stem cells which can generate myelin forming cells, and on preclinical systems for engineering these cells to target their migration into demyelinated lesions to promote brain repair.
In collaboration with Celgene, a New Jersey-based biotech firm, Dr. McKinnon was awarded a $300,000 grant from the NJ Commission on Science & Technology entitled Gliogenic Potential of Human Placental Stem Cells to identify mechanisms of glial cell generation from human placental cells. More recently, Dr. McKinnon was awarded $300,000 from NJCST for “Stem Cell Therapeutics: PDGF-Directed Glial Migration.” This study will focus on engineering stem cells so that they home into a site of injury for brain repair. In addition, $300,000 from the $2.5M Core Facility Program Project Grant was awarded to Drs. McKinnon, Pirotta, Roth and Casaccia for the "Bioengineering hES cells". This work will focus on genetic engineering of human stem cells.
Daniel Medina, M.D.
UMDNJ-RWJMS/CINJ, Assistant Professor
The Medina laboratory studies the pathogenesis of human leukemia and lymphoma. In particular, they are interested in a rare and incurable form of Non-Hodgkin’s lymphoma known as mantle cell lymphoma (MCL). There is increasing evidence that cancers contain a small subset of cells with stem cell-like properties often referred to as cancer stem cells (CSC). CSCs are often drug resistant and can self-renew to generate additional CSC, and also differentiate into diverse cancer cells with limited proliferative potential as found in the bulk tumor. The existence of CSCs may explain why there are so many recurrences, after chemotherapy. We have been focusing on the identification and characterization of cancer stem cells (CSC) from patients with MCL. We are interested in defining the CSC supportive microenvironment, and the mechanisms that function in the CSC niche to promote a balance of self-renewal and differentiation. We have defined an in vitro system supported by human bone marrow mesenchymal stem cells (hMSC) that can maintain undifferentiated normal and MCL-CSC for a prolonged period of time. This co-culture system is being used as a model to study interactions between MCL-CSC and hMSC and the genetic and signaling pathways initiated by these interactions. The long-term objective is to use the knowledge gained to develop targeted therapy against cancer stem cells and/or their supportive niches.
In 2007, Dr. Daniel Medina was awarded $300,000 from the NJCST for “Identification and Characterization of Mantle Cell Lymphoma Stem Cells.” This project will test the hypothesis that Mantle Cell Lymphoma (MCL) is composed in part by MCL stem/progenitor cells that act as "seeds" and that these cells have the capacity to give rise to the bulk tumor and are responsible for patient relapse.
Eric Moss, Ph.D.
UMDNJ-SOM, Associate Professor, Dept of Mol Biol.
Dr. Moss’ research has identified new genes that promote neuron formation from stem cells that may be valuable for the repair of spinal cord and brain injuries.
Robert Nagele, Ph.D. UMDNJ-SOM, NJ Institute for Successful Aging
Mesenchymal stem cells (MSCs) are rare, adult somatic stem cells with enormous clinical potential but require extensive cultivation in the laboratory prior to clinical use. So far, MSCs have shown a limited lifespan and may lose some stem cell characteristics relatively early during culture. In 2007, Dr. Nagele received $297,080 from the NJCST for the proposal entitled “Genomic Stability, Chromatin Remodeling and Differentiation Potential of Mesenchymal Stem Cells”. This study will shed new light on how and why MSCs change in culture and aims to ensure the development of safe protocols for their therapeutic use.
Richard Nowakowski, Ph.D.
UMDNJ-RWJMS Professor, Dept of Neuroscience & Cell Biology
The research in the Nowakowski lab focuses on the behavior of proliferating cells in the brain of normal and mutant mice. In the developing brain, they study neurostem cells that produce the cells of the neocortex and the retina. In the adult brain, they study adult neurogenesis in the dentate gyrus and subventricular zone. His lab also studies cell proliferation as a response to the injury of the spinal cord. In all of these cases the proliferating cells are stem cells or candidates to become stem cells. Dr. Nowakoskwi is interested in understanding how gene expression controls the fate of the cells that are produced from this cell proliferation. He uses a variety of methods including genetic differences and genomic approaches. His lab integrates their data using the methods from the new field of systems biology and bioinformatics.
Dr. Nowakowski is a long-time stem cell researcher. He has been studying the proliferating cells of the brain (i.e., neurostem cells) for over 30 years. In 2006, He was awarded a $300,000 NJ CST grant entitled Molecular Circuitry of “Stemness” in the Developing CNS. Dr. Nowakowski received his Ph.D. from Harvard University and has been a faculty member at Robert Wood Johnson Medical School for over 20 years. He is also a New Jersey Professor of Spinal Cord Research.
Sidney Pestka, M.D. UMDNJ-RWJMS, Professor & Chair, Dept of Mol Genetics
IFN-2a, developed by Dr. Pestka, was the first recombinant interferon approved for clinical trials in 1981. Since that time, the interferons have been found to be useful in a variety of cancers and viral diseases, especially for treatment of Hepatitis B and C. However, because of the side effects seen with systemic high dose interferon treatment, interferon has not lived up to early expectations regarding its use against cancers and a broad variety of viral indications. In cancer treatment, the interferons produce side effects that can be debilitating to patients so that high doses sufficient to eliminate tumors effectively cannot usually be reached in systemic injections. A major possibility to minimize side effects is to localize the interferons in the tumors - a process that might be accomplished with stem cells. Marrow-derived stem cells that are injected into animals or patients predominantly localize into the microenvironment of tumors. These stem cells could be used to deliver biotherapeutics that are effective against tumors directly to the tumors and minimize the presence of the biotherapeutics in the general circulation where they produce toxic side effects. Minimization of toxic side effects of agents such as the interferons would enable the interferons to be used to treat cancers effectively. However, because the standard alpha interferons used worldwide are generally not sufficiently potent to minimize growth of tumors or destroy tumors, Dr. Pestka’s laboratory has developed a number of novel human alpha interferons that are much more potent than the standard interferons. Their work is designed to use the new alpha interferons with high antiproliferative activity to be delivered to tumors via marrow derived stem cells to treat a wide variety of cancers.
Dr. Pestka receive a $300,000 research grant in 2007 from the NJCST for “Use of Stem Cells for Delivery of Biotherapeutics for the Treatment of Cancers.” The goal of this project is to utilize stem cells to deliver biotherapeutics to minimize the side effects of treatment with the interferons, thus enabling these molecules to treat cancers.
Nicholas Ponzio, Ph.D.
UMDNJ-NJMS, Professor, Dept of Path & Lab Medicine
Associate Director and CEO for the Neurological Institute of NJ
Dr. Ponzio serves as Vice Chair for Academic Affairs in the Department of Pathology and Laboratory Medicine, as Associate Director and Chief Operating Officer for the Neurological Institute of New Jersey (NINJ), and as Interim Director of the Brain Cell Regeneration program at NINJ. He is interested in cancer immunotherapy using human umbilical cord blood cells.
Ling Qin, Ph.D.
UMDNJ-RWJMS Instructor, Dept of Physiology
Dr. Qin’s research has focused on the parathyroid hormone (PTH) treatment of osteoporosis. PTH stimulates bone formation by acting through the bone forming cell, the osteoblast, but its mechanism is unknown. Dr. Qin believes that epidermal growth factor receptor (EGFR) signaling plays an important role in regulating mesenchymal stem cell proliferation and the subsequent differentiation of these cells into multiple tissue cells, including osteoblasts. Through a combination of in vitro and in vivo methods, she studies how PTH’s action on osteoporosis might occur through the increased expression of amphiregulin, an EGFR ligand, therefore expanding the mesenchymal stem cell pool to achieve more osteoblasts in bone. Her research could lead to therapies for osteoporosis and other disorders affecting bone density. Dr. Qin’s research entitled “PTH-Mediated EGFR Signaling in Stromal Stem Cell Growth and Multidifferentiation” has garnered significant support from the NJCST.
Pranela Rameshwar, Ph.D.
UMDNJ-NJMS, Professor, Dept of Medicine
Dr. Pranela Rameshwar is a leading investigator in stem cell research at UMDNJ-New Jersey Medical School. Using hematopoietic and mesenchymal stem cells as model systems, her research interests have focused on stem cell biology in a spectrum of disciplines ranging from hemotopoiesis to neurobiology to cancer. Among her many projects, Dr. Rameshwar studies breast cancer stem cells and why such cells have a tendency to migrate to bone marrow, an area of the body where breast cancer tends to metastasize. Understanding of this biological process could lead to new therapies to reverse or prevent the spread of breast cancer to the bone. Her laboratory also studies how adult mesenchymal stem cells differentiate to become neurons, which could lead to treatments for neuronal injury incurred by trauma or neuro-degenerative disease.
Monica Roth, Ph.D.
UMDNJ-RWJMS, Professor, Dept of Biochemistry
Dr. Roth research focus has been on vector development for gene therapy. Cell therapy, in particular stem cell therapy, offers benefits beyond that of gene therapy. Dr. Roth’s research aims at combining the power of gene therapy with that of stem cell therapy. Hematopoietic stem cells are ideal targets for human gene therapy, and when drug resistance genes are introduced into these Hematopoietic stem cells, the cells can resist destruction by high dose chemotherapy when used in autologous cell replacement therapies for patients with hematologic disorders. Drug resistance genes are frequently introduced using retroviral vectors; however, the retroviral vectors are not efficient at targeting hematopoietic stem cells. Dr. Roth has developed a method to select for productive retroviral entry using novel receptor proteins. This method serves as a means of targeting gene delivery to cells that are not well characterized, including hematopoietic stem cells. The ultimate goal of her current work is to isolate a novel retroviral particle that efficiently and specifically can recognize and deliver genes to hematopoietic stem cells. Dr. Roth has received significant funding from the NJCST to support this work.
Arnold Rubin, M.D.
UMDNJ-RWJMS, Professor, Dept of Medicine
Director, Stem Cell Transplantation Program of CINJ
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The Stem Cell Transplantation Program is conducted in conjunction with the Robert Wood Johnson University Hospital for in-patient care. Physicians actively perform stem cell transplants on a variety of illnesses where this treatment is indicated. These include acute and chronic leukemia’s, myelodysplasia, lymphomas both low and high-grade, chronic lymphocytic leukemia, Hodgkin’s disease and myeloma. Both autologous and allogeneic transplants are performed. The sources of transplant include matched siblings as well as matched unrelated donors from the National Marrow Donor Program. The program also performs cord blood transplants. There are a series of experimental transplants, which include the use of haploidentical sibling transplants. The program is using depletion of T-cells and has an experimental program, which transplants haploidentical sibling stem cells and lymphocytes without an attempt for permanent engraftment. Additional experimental protocols include prevention of graft vs. host disease with extra corporeal radiation as well as a program for preventing the mucusitis of transplant with the use of an epithelia cell growth factor. The program is certified by FACT as well as the National Marrow Donor Program.
Junichi Sadoshima, M.D., Ph.D.
UMDNJ-NJMS, Professor, Dept of Cell Biol & Mol Medicine
Although adult stem cells implanted into the heart can differentiate into heart cells, at present, the efficiency of such treatment has been far below expectation. One reason could be that the current stem cell treatment is not able to generate sufficient numbers of functional heart cells. Dr. Sadoshima’s goal is to find the mechanism by which the efficiency of adult stem cell differentiation into heart cells is dramatically improved. Using various in vitro techniques and a unique animal model for heart failure, Dr. Sadoshima’s current research tests the hypothesis that specific modulation of intracellular signaling events can alter the efficiency of adult stem cell differentiation into heart cells and improve the heart function during heart failure. Elucidating the molecular mechanisms by which the adult stem cells differentiate into heart cells would allow the development of novel strategies to facilitate regeneration of the heart, which could become a fundamental treatment for a wide variety of heart diseases. In 2006, Dr. Sadoshima won a $300,000 award from the NJCST for the project “Mechanisms of Mesenchymal Stem Cell Differentiation”.
Biagio Saitta, PhD
UMDNJ-RWJMS, Associate Professor, Dept of Medicine
Coriell Institute of Medical Research, Laboratory of Stem Cell and Matrix Biology
Cardiovascular disease impacts millions of lives worldwide. Heart tissue responds to damage with scarring, fibrosis, and hypertrophy. The resulting loss of function limits the quality of life for most patients. Transplants are possible for many cardiac conditions, but donors are limited. The new field of regenerative medicine utilizes multi-potent stem cells as a promising strategy to heal damaged tissue and preserve or regain function. Human mesenchymal stem cells (MSCs) from bone marrow have been shown to target damaged myocardium in animal models of ischemic heart disease and infusions of such adult stem cells can limit fibrosis and improve function, leading to the first U.S. clinical trials using allogenic adult MSCs to treat patients with heart attacks. However, the mechanisms that stem cells use to improve and support damaged myocardium remain largely unknown. Dr. Saitta and colleagues use an in vitro model of myocardial damage to study the response of MSCs to cardiac damage. Their central hypothesis is that the introduction of MSCs affects pathologic remodeling of heart tissue by reducing the fibrotic response through the modulation of extracellular matrix (ECM) gene expression. Their approach will allow the identification of specific secreted factors and changes in ECM gene expression that result from the stem cell response. These studies can lead to information that will be directly relevant for management of myocardial infarction. These studies also can provide important new information on the action of MSCs and new targets for therapeutic discovery. They use MSCs derived from umbilical cord blood, a readily-available and non-controversial source of human stem cells.
Dale Schaar, M.D., Ph.D.
UMDNJ-RWJMS, Assistant Professor, Dept of Medicine
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Dr. Schaar is a practicing oncologist and is a member of the Stem Cell Transplantation Program of CINJ which treats patients with various hematological disorders (see Arnold Rubin for more complete description). He is also a member of The CINJ Hematologic Malignancies Program which is a university-wide multi-disciplinary group of disease-oriented physicians, scientists, nurses, social workers and other staff members dedicated to optimizing therapy for patients with acute and chronic leukemias, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, multiple myeloma, myelodysplasia, myeloproliferative diseases, and other hematologic malignancies.
Michael Shen, Ph.D.
UMDNJ-RWJMS, Professor, Dept of Pediatrics
Center for Advanced Biotechnology and Medicine
Dr. Shen is pursuing studies of embryonic stem cells as a logical outgrowth of his work on the molecular regulation of mouse embryogenesis. His research investigates the molecular mechanisms by which embryonic stem cells remain in the undifferentiated state, and how they make their initial decisions to generate specific cell types once released from the undifferentiated state. Current studies explore the regulation of pluripotent stem cells of the early mouse embryo in vivo and embryonic stem cells in culture.
Dr. Shen’s work does not focus on a specific disease, but rather on understanding the basic biological processes that regulate embryonic stem cell behavior. Any therapeutic use of stem cells will require understanding the molecular mechanisms of their directed differentiation into specific cell types. Increasing our knowledge of the mechanisms by which stem cell state is maintained in the pre-implanted embryo will also be relevant for improving the success rate of in vitro fertilization. Dr. Shen’s work entitled “Role of the Nodal signaling pathway in regulation of embryonic pluripotency” has been supported by the NJ CST.
Yufang Shi, D.V.M., Ph.D.
UMDNJ-RWJMS, Professor, Dept of Mol Genetics, Micro & Immuno
New research carried out by Dr. Yufang Shi and his colleagues aims to combat various immune disorders and to improve the success of bone marrow transplants. In studying mesenchymal stem cells (MSCs) isolated from adult bone marrow, Dr. Shi found that these cells are very potent at suppressing immune responses. In a recently published article, Dr. Shi’s group reported that treatment with relatively few of these MSCs can prevent the rejection of skin transplants made between mismatched mice. They also found that MSCs can inhibit graft-versus-host disease (GvHD) in mice. Dr. Shi’s group is currently examining the molecular mechanisms underlying this immunosuppressive function of MSCs, with hopes to further improve the efficacy of clinical therapies using MSCs. For example, they now know that exposing MSCs to certain cell factors dramatically enhances their immunosuppressive effect. Dr. Shi’s group is now actively working with doctors at the Cancer Institute of New Jersey to set up clinical trials to treat leukemia patients who have developed GvHD after bone marrow transplantation. They are also exploring the potential use of MSCs in the treatment of some common autoimmune diseases, such as rheumatoid arthritis, autoimmune diabetes, and multiple sclerosis.
Dr. Shi won two awards from the NJCST, with support for the project entitled “Immunobiology of Mesenchymal Stem Cells” granted in 2006 to investigate the mechanisms underlying stem cell mediated immune tolerance and its use in treatment of autoimmune disorders. In 2007, Dr. Shi, was awarded $300,000 for “Mechanisms of Mesenchymal Stem Cell Induced Immunosuppression” to investigate how adult stem cells affect immune responses and develop protocols for the treatment of autoimmune diseases and maintenance of transplanted tissue and organs.
Roger Strair, M.D., Ph.D.
UMDNJ-RWJMS, Associate Professor, Dept of Medicine
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Bone Marrow and Peripheral Stem Cell Transplantation Program
Dr. Strair is the Director of the Bone Marrow and Peripheral Stem Cell Transplantation Program. The program is engaged in two aspects of clinical stem cell research. First, they utilize hematopoietic stem cell transplantation as a therapeutic modality for patients with acute or chronic leukemia, myelodysplasia, myeloproliferative disease, multiple myeloma, non-Hodgkin's lymphoma, Hodgkin's lymphoma and aplastic anemia. Clinical studies are focused on developing new transplant-related strategies to improve the therapy of these diseases. In another line of research, they are also investigating the stem cell hierarchy of these diseases to identify new cellular targets. A clinical trial using a new modality to target acute myelogenous leukemia stem cells is underway.
Dorothy Vatner, M.D.
UMDNJ-NJMS, Professor, Cardiovascular Research Institute
Recent scientific findings have identified heart cells that may act as cardiac stem cells, enabling heart cell generation and replenishment. Dr. Vatner studies how these cardiac stem cells might work and also how these stem cells may act differently in males and females.
Stephen Vatner, M.D.
UMDNJ-NJMS, Professor & Chair, Dept of Cell Biol and Mol Medicine
Director, Cardiovascular Research Institute
Dr. Vatner’s research addresses the question of whether direct injection of bone marrow stem cells into heart tissue next to the damaged tissue will lead to the creation of new tissue and improved contraction function.
Ian Whitehead, Ph.D.
UMDNJ-NJMS, Associate Professor, Dept of Microbiology & Mol. Genetics
The Whitehead laboratory conducts research in the field of mammalian signal transduction, with a particular interest in small G proteins and their contribution to human cancer. More specifically, they have focused their research efforts on the identification and analysis of those signaling pathways that are regulated by members of the RhoGEF family. The RhoGEFs are a structurally-related family of oncoproteins that share an approximately 200 amino acid stretch of sequence similarity with Dbl, a transforming protein that was isolated from a diffuse B cell lymphoma. The important role that RhoGEF controlled signaling pathways play in multiple aspects of oncogenic transformation has been well documented. Bcr and Dbs are two members of the RhoGEF family that are studied extensively in this laboratory. We have been developing both Dbs and Bcr as model systems to study how the deregulated expression of a mammalian RhoGEFs can trigger oncogenic signaling pathways. Central to our understanding of Dbs and Bcr mediate oncogenicity will be our ability to determine how they interact with regulatory factors, and our ability to identify downstream signaling pathways that are responsible for the transformed phenotype.
Teresa Wood, Ph.D.
UMDNJ-NJMS, Professor, Dept of Neurology & Neuroscience
A major research effort in Dr. Wood’s laboratory involves endogenous stem and progenitor cell populations. A major focus of the laboratory is on the expression and function of insulin and insulin-like growth factor (IGF) receptors in various stem cell lineages including neural, mammary and mesenchymal.
There are two primary projects in the laboratory that focus on stem cells. In the nervous system, Dr. Wood is investigating the signaling pathways important for how the neural stem/progenitor cells (NSPs) proliferate or differentiate, particularly with reference to the glial cell lineage.
In addition to studies of NSPs, Dr. Wood’s laboratory has been working on new markers for endogenous stem cells in mammary/breast tissue. A new area of investigation under Dr. Wood’s laboratory focuses on elucidating a new marker for a subset of breast epithelial cells which have the potential to give rise to specific cell types during normal breast development and to specific types of breast tumors. This novel marker may identify a population of undifferentiated breast tumor stem or progenitor cells.
Dale Woodbury, Ph.D.
UMDNJ-RWJMS, Assistant Professor, Dept of Neuroscience & Cell Biology
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Dr. Woodbury is interested in stem cell plasticity. Dr. Woodbury identified stem cells in a number of extra-embryonic tissues, including the placenta and chorion. Unlike previously described amniotic epithelial and mesenchymal cells, these amnion-derived stem cells (ADSCs) exhibit the prototypical stem cell traits of long term self renewal, multi-differentiation, and clonogenicity. These cells can be used as an alternative stem cell population to embryonic stem cells. They have the potential to be utilized in any clinical application involving cell replacement, including, but not limited to, Alzheimer’s disease, Parkinson’s disease, spinal cord injury, ischemic events (heart attack, stroke), heart failure, diabetes, osteoporosis, liver failure and kidney disease.
In 2007, Dr. Woodbury was awarded $268,533 from the NJCST to study the “Plasticity of Amnion-Derived Stem Cells In Vitro and In Vivo.”
Mengqing Xiang, Ph.D.
UMDNJ-RWJMS, Associate Professor of Pediatrics
Center for Advanced Biotechnology & Medicine
Dr. Xiang’s research interests center on understanding the molecular mechanisms that govern the determination and differentiation of the highly specialized sensory neurons. His laboratory employs molecular genetic approaches in animal models to identify and study transcription factors that are required for programming development of the retina, inner ear, and somatosensory ganglia. In addition, they explore the possible linkage of these factors to some hereditary sensorineural diseases including blindness and deafness and develop animal models for these disorders.
Dr. Xiang’s laboratory utilizes two general approaches to understand the biological roles that a transcription factor gene plays during vertebrate neurogenesis. One is a loss-of-function approach involving targeted gene disruption in mouse embryonic stem (ES) cells to produce mice deficient for the gene. The other is a gain-of-function approach involving retrovirus-mediated overexpression of the gene in the chick and mouse embryonic tissues. These complementary approaches have allowed him to achieve a comprehensive understanding of the crucial functions of the Brn3 subfamily of POU domain transcription factors in senserineural development.
In 2007, Dr. Xiang was awarded $300,000 from the NJCST for “Controlled Differentiation of Inner Retinal Cell Types from Stem Cells”.
Peter Yurchenco, M.D., Ph.D.
UMDNJ-RWJMS, Professor, Dept of Path & Lab Medicine
Dr. Yurchenco is head of the Matrix Biology Laboratory. Research in the laboratory focuses on basement membranes, which are evolutionarily ancient cell-associated extracellular matrices (ECMs) required for embryonic development and for normal tissue functions. They are found under epithelial layers, around the endothelium of blood vessels, and surround muscle, peripheral nerve, and fat cells. Mutations affecting the laminin, collagen, and proteoglycan components of these ECMs cause diseases of muscle, kidney, nerve, brain and skin. Long term goals of the laboratory are to understand how different basement membranes assemble and influence cell behavior at the molecular level and how this process regulates embryonic differentiation. Another goal is to understand how basement membrane laminins affect neuromuscular function.
Marco Zarbin, M.D., Ph.D.
UMDNJ-NJMS, Professor & Chair, Dept of Ophthalmology & Visual Science
Dr. Zarbin and his colleagues are studying the effect of transplanting embryonic and adult stem cells to treat diseases such as retinitis pigmentosa and age-related macular degeneration. They’re investigating whether transplanting these cells may slow the cell degeneration process and/or also create a more viable surface for retinal pigment epithelium migration or transplantation.