banner-stem-cell-symposium

Symposium speaker profiles

 

Martin Grumet, Ph.D.
W.M. Keck Center for Collaborative Neuroscience, Rutgers Stem Cell Research Center, Rutgers University, Piscataway, NJ

Biography
Dr. Martin Grumet is Professor of Cell Biology and Neuroscience in the Division of Life Sciences at Rutgers University, Director of the Rutgers Stem Cell Research Center and Associate Director of the W.M. Keck Center for Collaborative Neuroscience. His lab focuses on novel applications of molecules and stem cells to neurological disorders.  Projects to promote functional recovery after spinal cord injury have been successful using neural stem cell transplantation,  siRNAs to inhibit protein synthesis, and human bone marrow stem cells.

Dr. Grumet received his B.Sc. in Physics from The Cooper Union, his Ph.D. in Biophysics at Johns Hopkins University, and did his Post-Doctoral Fellowship in Developmental and Molecular Biology at The Rockefeller University.

Contact information
mgrumet@rci.rutgers.edu

Presentation
Factors Secreted by Mesenchymal Stromal/Stem Cells (MSC) Protect the Injured  Central Nervous System (CNS)

Abstract
MSCs have been used extensively in transplantation because of their abilities to home to bone marrow, and to differentiate into cells such as chondrocytes that promote joint repair. MSC have also been found to be anti-inflammatory, which provides benefit in many inflammatory conditions including neural trauma. Our lab is studying human bone marrow mesenchymal stem/stromal cells (MSC) for their anti-inflammatory effects in spinal cord injury (SCI). We have shown that minimally invasive lumbar delivery of MSC soon after SCI has anti-inflammatory effects in rats. Because of the importance of initiating anti-inflammatory effects as soon as possible after SCI, it is critical to develop forms of MSC that can be ready for use in a wide range of patients. Towards that goal, MSC were encapsulated into alginate microspheres that were injected into the lumbar spinal cord. Delivery of the encapsulated MSC one day after SCI decreased the inflammatory response and improved recovery. Moreover, human MSC are protected from the host by encapsulation in alginate and they persist for long periods in the rat spinal cord in contrast to unprotected human MSC that disappear within several days. Thus, encapsulation may allow HLA unmatched human cells to be transplanted widely. Our goal is to optimize the activated MSC for minimally invasive delivery and to identify their secreted factors that mediate the response in SCI.

Acknowledgements
Supported by grants from NIH and NJSCSCR.

 

Uma Lakshmipathy, Ph.D.
Principal Scientist, Cell Biology and Stem Cell Sciences, Life Technologies
Carlsbad, CA

Biography
Dr Uma Lakshmipathy has a Ph.D. in Life Sciences and is currently a Director at Life Technologies. She has been involved in the field of stem cells for over a decade and has published over 50 papers in reputed journals.   Her research interests are regulation of stem cell maintenance, development of technologies for generation, identification, characterization, and differentiation of pluripotent stem cells.

Contact information
uma.lakshmipathy@lifetech.com

Presentation
TaqMan® Human Pluripotent Stem Cell Scorecard

Abstract
Rapid progress in technologies for the generation of footprint-free induced pluripotent stem cells (iPSC) has led to creation of patient derived stem cells that are valuable tools in drug discovery and translation into cell therapy.   The resulting iPSC derived from diverse patient sources using different methods and conditions has created a challenge for rapid and comprehensive characterization.   Traditional characterization methods are based on biomarker expression that utilizes a combination of in vitro and in vivo cellular analysis to confirm pluripotency and trilineage differentiation potential. Such methods are subjective and not amenable to high throughput confirmation.  
 
TaqMan® hPSC Scorecard™ Panel is a comprehensive gene expression real-time PCR assay that can be utilized for rapid generation of quantitative transcriptome data. High density and medium density gene expression analyses were used to identify the optimal genes that define the pluripotent state and detect early stages of differentiation into cell types representative of the three germ layers.  The resulting TaqMan® Human Pluripotent Stem Cell Scorecard consists of 93 assays comprising a combination of controls, pluripotent and lineage specific genes.  Resulting expression data is analyzed using cloud-based analysis software that compares the expression pattern against a reference standard generated using multiple functionally validated ESC and iPSC lines.  This system was successfully used to test several ESC and iPSC lines in their undifferentiated state as well as lines that were spontaneously differentiated and directed differentiated into specific lineages,  to confirm their pluripotency and determine their differentiation potential.

Gabsang Lee, Ph.D., D.V.M.
Assistant Professor, New York Stem Cell Foundation-Robertson Investigator, Institute for Cell Engineering, Department of Neurology and Neuroscience, School of Medicine, Johns Hopkins University
Baltimore, MD

Biography
TBD

Contact information
glee48@jhmi.edu  

Learn more about Dr. Lee’s lab:

Presentation
Disease modeling of peripheral nervous system using human neural crest

Abstract
Patient-specific human induced pluripotent stem cell (hiPSC) offers unprecedented promise in disease modeling and drug discovery by providing unlimited number of symptom-relevant cells.

Taking advantage of our novel methodology of direct differentiation and prospective isolation of neural crest (NC) from human pluripotent stem cells, we successfully modeled Familial Dysautonomia (FD) with hiPSC technology, which gave us clues for disease pathogenesis. To extend our efforts of drug validation, we set out large-scale compound (over 7,000) screening study with symptom-relevant NC derived from FD-hiPSCs, which lead us to identify potential therapeutic compounds.

Moving toward, our lab is currently exploring fate determination of different neural crest subtypes, including nociceptive neurons, sympatho-adrenal lineages, Schwann cells and recently successfully convert human postnatal fibroblasts into induced neural crest fate, providing additional insights on peripheral nervous system disorders.

  Scott Lipnick, Ph.D.
Director of Scientific Programs, New York Stem Cell Foundation
New York, NY

Biography
Scott Lipnick, PhD, joined NYSCF in Spring 2012 as the Director of Scientific Programs. At NYSCF, he oversees partnerships with external scientific groups, intellectual property and technology transfer, and the external funding programs.  Prior to joining NYSCF, he most recently served as an American Association for the Advancement of Science (AAAS) Science and Technology Policy Fellow at the National Institutes of Health Center for Regenerative Medicine (NIH CRM). At NIH CRM, he managed the intramural stem cell pilot grant program, performed oversight of intellectual property issues related to stem cell projects to ensure there would be a clear path to the clinic, and facilitated seminars and working groups to develop teams to translate stem cell technologies. Prior to his time at the NIH, Scott obtained his PhD in Biomedical Physics from the University of California, Los Angeles, and a BS in Physics and Economics from Brandeis University.

Contact information
SLipnick@nyscf.org

Presentation
High Throughput iPS Cell Generation and Differentiation for Disease Modeling

Abstract
The NYSCF Global Stem Cell Array enables derivation and manipulation of stem cell lines in a high-throughput, parallel process using automation. Standardization and scale-up capabilities achieved through this automated process are critical to reduce methodological variability to uncover true biology. We are combining advances in stem cell derivation, including non-integrating mRNA/miRNA reprogramming technology, with robotics to functionalize human genetics.

 

Zhiping Pang, Ph.D.
Assistant Professor, Robert Wood Johnson Medical School, Dept. of Neuroscience & Cell Biology, The Child Health Institute of NJ, Rutgers University
New Brunswick, NJ

Biography
Zhiping Pang Ph.D., assistant professor of Neuroscience and Cell Biology, resident member of the Child Health Institute of New Jersey, and associate member of the Human Genetics Institute of New Jersey. He obtained his Ph.D. at UT Southwestern Medical Center.  Zhiping’s research focuses on understanding how synaptic transmission is regulated in the brain.  Working with Drs. Tom Südhof and Marius Wernig at Stanford, he had helped developing induced neuronal (iN) cell technology that can directly convert both mouse and human skin fibroblasts directly into functional neurons. Currently his lab is interested in modeling human neuropsychiatric and neurological disorders by utilizing human neurons derived from various sources including the induced pluripotent stem cells.

Contact information
pangzh@rwjms.rutgers.edu

Presentation
Utilizing human neurons to understand neuropsychiatric disorders

Abstract
The pathogenesis and etiology of many neuropsychiatric diseases, such as addiction, eating disorders, schizophrenia, autism spectrum disorders (ASDs) and Rett syndrome (RTT), remain an enigma because studies of the human brain in these patients are largely restricted to brain imaging or post-mortem analyses. Cellular analysis, such as characterization of synaptic transmission, is impossible due to the inaccessibility of human neurons from patients. Recent advancement in stem cell biology has made more in-depth analysis possible. However, modeling of human neuropsychiatric diseases is still in its’ infancy. Current technology of generating neurons from iPS cells is difficult, variable and time consuming. Development of better differentiation protocols and reproducibility of results across platforms are pressing questions to be addressed. I will describe three different methodologies in generating human neurons including: 1) direct conversation of human fibroblasts into functional neurons, i.e. induced neuronal (iN) cells; 2) generating dopaminergic neurons from iPS cells using small molecules and using iN technology; and 3) generating neurons from iPS cells via neuroprogenitor cells. Then I will describe characterization of human neurons derived from patients carrying addiction risk genes, specifically the D398N SNP of nicotinic receptor alpha5 subunit, and from RTT patients. It is clear that with “disease-in-a-dish” models using iPS cell-derived neurons, while they may capture cell-intrinsic properties and synaptic deficits of diseased neurons, special precautions need to be taken into account for the enormous variability in the neuronal subtype composition and neural network identities of iPS cell-derived models for neuropsychiatric disorders.

 

Hatem Sabaawy, M.D., Ph.D.
Director of Production GMP Facility for Cell and Gene Therapy; Assistant Professor of Medicine, Medical Oncology
Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Cancer Institute of New Jersey
New Brunswick, NJ

Biography
Hatem Sabaawy, MD, PHD (Ha`tem Sab awi) is an assistant Professor of Medicine at Rutgers/RWJMS, and a member of the Division of Medical Oncology at Rutgers CINJ. He had his medical and graduate training at New York Medical College in Valhalla, NY. Dr. Sabaawy joined CINJ 4 years ago from the NIH/NCI where he was a Transplant Fellow in the Transplantation and Immunology Branch of the Center for Cancer Research at NIH in Bethesda, MD. His work at CINJ is focused on translational research studies of normal and tumor stem cell development utilizing Zebrafish models to identify stem cell markers, genetic modifiers and drug targets that enhance our understanding of cancer development and ultimately improve cancer survival.

A parallel research effort for him is to study human mesenchymal stroma cell (MSC)-based therapy and transplantation in regenerative medicine. Dr. Sabaawy and his colleagues are collaborating on international clinical trials for utilizing MSCs-based cell therapy for injury repair.

Contact information
sabaawhe@cinj.rutgers.edu

Presentation
Development of small molecule inhibitors targeting cancer stem cells

Abstract
Several lines of evidence support the concept that relapse in cancer patients occurs due to the presence of cancer stem cells (CSCs). Located at the top (or the center) of the tumor hierarchy, CSCs can self-renew and also generate non-CSC progeny, which form the tumor bulk (differentiated progeny). Emerging data revealed a highly complex and dynamic cellular composition of tumors. The extreme tumor heterogeneity that was exposed suggests that distinct CSCs might exist on top of competing tumor subclones that comprise the genetically heterogeneous tumors. CSCs have the ability to survive treatment by adapting resistance mechanisms for derailing self-renewal regulation, evading apoptotic pathways, and retaining high levels of drug efflux membrane transporters, and high DNA repair capacity. The main pathways controlling CSC self-renewal include Bmi-1, Oct3/4, Hedgehog (Hh), Wnt/β-catenin, Notch signaling, Hox gene family, PTEN/Akt pathway, efflux transporters such as ABCG markers of self-renewal, and upregulated telomerase activity. These pathways are now all potential targets for CSC-targeted therapy and cancer drug discovery. Accordingly, there is an urgent need to identify new compounds targeting these self-renewal pathways, and to develop strategies to tailor combinations of these therapies against the genetically heterogeneous and molecularly diverse CSCs. I will be discussing these recent advances in the CSC field, and efforts in my laboratory to develop CSC-targeted therapies. Moreover, I will describe a novel zebrafish xenograft assay for estimating the frequencies of CSCs from multiple cancer cell lines and primary patient samples. I will also further elucidate the value of utilizing both zebrafish xenografts of primary CSCs, and pathway-specific transgenic zebrafish reporter lines to identify small molecule inhibitors targeting self-renewal and cell cycle regulatory pathways.

Acknowledgements
The studies are supported by a pilot award from the Wellcome Trust, NCI/NIH cancer center grant to Rutgers Cancer Institute of New Jersey, and a synergy award from the Department of Defense. Supported by grants from NIH and NJSCSCR.

 

Ren-He Xu, M.D., Ph.D.
Associate Professor, Genetics and Developmental Biology; Director, University of Connecticut Stem Cell Core
Department of Genetics & Developmental Biology, University of Connecticut Health Center
Farmington, CT

Biography
Dr. Ren-He Xu is an associate professor of Department of Genetics and Developmental Biology, University of Connecticut Health Center, and the director of University of Connecticut-Wesleyan University Stem Cell Core.
He obtained M.D. from South China University and Ph.D. From University of Tokyo. He had postdoctoral training on developmental biology at the NIH and was a Senior Scientist of WiCell Research Institute studying human embryonic stem cells directed by Dr. James Thomson. He joined UConn Health Center in 2006.

Contact information
renhexu@uchc.edu

Presentation
A hESC-derived, potential therapeutic for multiple sclerosis

Abstract
Human embryonic stem cells (hESCs) have been widely used for study of human development, disease modeling, and tissue regeneration. We have explored a novel application of hESCs - using hESC-derived mesenchymal stem cells (hES-MSCs) to treat an autoimmune disease, multiple sclerosis (MS). hES-MSCs outperform bone marrow (BM) MSCs in improving symptoms in a mouse MS model and immunosuppression in vitro. This is largely related to the lower expression of the pleiotropic cytokine IL6 in hES-MSCs than BM-MSCs, and the distinct ability of hES-MSCs to extravasate and migrate into inflamed tissues in the central nervous system.

Acknowledgements
Connecticut State Stem Cell Research Fund Program for grants. Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine for some BM-MSC samples.