SwitchGear Pathways Grant Program
SwitchGear Genomics is pleased to announce our grantees for the SwitchGear Pathway Biomarker Sets. Meet our winners below!
Who: Dr. Alex Swarbrick, Group Leader
Institution: Garvan Institute of Medical Research, Australia
Product Highlight: SwitchGear p53 Biomarker Set.
We have recently identified that microRNA mir380 represses expression of p53 in neuroblastoma, breast cancer, and embryonic stem cells (Manuscript under review). We have also identified a role for p53 in the senescence response to oncogenic activation in mammary cells in vitro and in vivo (Swarbrick et.al, PNAS 2007). We aim to further study how these pathways act to regulate p53 activity and its downstream effectors. One of the primary limitations to our work is the difficulty in measuring p53 protein expression and activity. We have previously used Switchgear p53 reporters to monitor p53 transcriptional activity. The p53 biomarker set will provide us an invaluable tool to better analyse p53 pathway activity downstream in response to manipulations in the expression of microRNAs and genes that regulate senescence pathways, such as the ID family of proteins. We will expanding on our previous studies to identify other genes and microRNAs that regulate the senescence response. Using the biomarker panel, we can rapidly screen these candidates to identify the point in the p53 pathway at which they are acting.
Alex joined the Garvan Institute in January 2007 after undertaking postdoctoral studies in the laboratory of Nobel Laureate J. Michael Bishop at the University of California, San Francisco. His lab investigates the protein coding genes and microRNAs controlling the self renewal, differentiation and metastasis of cancer cells. He aims to expand the basic understanding of cancer progression to allow the development of better therapeutic strategies for hard-to-treat cancers. His lab uses a range of model systems, including 2D and 3D cell culture, animal models and human tissues.
Who: Dr. Sridhar Mani, Associate Professor and PI
Institution: Albert Einstein College of Medicine, USA
Product Highlight: SwitchGear Hypoxia (HIF1a) Biomarker Set.
Our laboratory works on nuclear receptors, transcription factors and cellular metabolism. One of our important laboratory focuses is to define the mechanisms of drug action in hypoxic cancer cells. Recently, we have focused on discovery of a completely novel panel of hypoxia targeted drugs, oxazine derivatives (Bioorg & Med Chem Lett 2009). Specifically, we will use the SwitchGear Hypoxia (HIF1a) Biomarker Set to determine the effects of our newly synthesized compunds (cpds) on HIF1a.
Dr. Sridhar Mani is currently the Director of the Phase I Program, Oncology, and leads a laboratory effort of nuclear receptor gene regulation and metabolism at the Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY. He is an Associate Professor of Medicine with appointments in Medicine and Genetics. In collaboration with Dr. Bhaskar Das, Assistant Professor (Medicinal Chemistry), Dr. Mani has recently developed novel compounds that combat hypoxia mediated cell growth and is interested in further exploration of mechanisms of action of these drugs.
Who: Dr. Paul Delgado, Postdoctoral Fellow
Institution: Gladstone Institute of Cardiovascular Disease, UCSF, USA
Product Highlight: SwitchGear NF-kB Biomarker Set
My research focuses on epigenetic silencing of transcriptional pathways during heart development and maintenance. Epigenetic processes activate tissue-specific transcription — however, little is known about non-specific pathways’ epigenetic repression. Thus, I am identifying transcriptional pathways epigenetically repressed in the mammalian heart and exploring the developmental and functional consequences of their de-repressio. We have recently uncovered an epigenetically repressed transcriptional pathway in the mouse heart, which de-repression causes cell junction remodeling and heart overgrowth. We found that a homeodomain transcription factor, which is repressed in the normal heart, partners with Nf-kB upstream the de-repressed pathway. In order to understand the mechanism by which these transcriptional activators affect cardiac cell junction and growth I will identify downstream target genes using the SwitchGear NF-kB Biomarker Set.
Dr. Delgado-Olguin is a postdoctoral fellow in the Gladstone Institute of Cardiovascular Disease in the laboratory of Benoit Bruneau. His research focuses on the epigenetic mechanisms regulating heart development and maintenance. Paul received a BS in biology and a PhD in biomedical sciences from the Universidad Nacional Autónoma de México (National Autonomous University of Mexico).
Who: Dr. Tewin Tencomnao, Assistant Professor
Institution: Chulalongkorn University, Thailand
Product Highlight: SwitchGear NF-kB Biomarker Set
We previously identified a number of Thai medicinal herbs with anti-psoriatic activity based on MTT assay using HaCaT cells. In addition, certain Thai herbs could provide an anti-psoriatic mechanism as it suppressed such expression maker for psoriasis as TGF-alpha based on our RT-PCR result. Recently, Nair et al. (2009) found an association between NF-kB pathways and psoriasis. Using the SwitchGear NF-kB Pathway Sets for transient transfection into HaCaT cells, we aim at measuring reporter gene levels to see which constructs (genes) can be modulated in the presence or absence of Thai herb treatment to better understand their anti-psoriatic mechanisms.
Dr. Tencomnao received his B.S. in Medical Technology with Honors at Chulalongkorn University in Thailand. He received his Ph.D. from the Medical College of Virginia. Dr. Tencomnao now serves as the Head of the Department of Clinical Chemistry at Chulalongkorn University. His research interests include roles of genetic polymorphisms in such multifactorial diseases as major depression and psoriasis.
Who: Dr. Mustapha Kandouz, Assistant Professor
Institution: Wayne State University, USA
Product Highlight: SwitchGear NF-kB Pathway Set
Our lab is interested in bioactive lipids in cancer and inflammation. In particular, metabolism by the lipoxygenases, has an established role in cancer. Our data show that activation of NF-κB is an essential aspect of the function of these lipoxygenases, through the regulation of specific pathways and functions related to cell homeostasis. In order to determine the major genes of the NF-κB-mediated pathway, that mediate these functions, we often use an approach of DNA microarray profiling. In one such study, We found that within the list of genes presenting different expression, over 25% belong to the NF-κB pathway. The SwitchGear NF-κB Pathway Sets will be a perfect tool to finalize our study and strengthen its value for publication. It will allow the identification of the mechanisms by which NF-κB signaling pathway is modulated. SwitchGear NF-κB Pathway activation will be assayed and the results analyzed in combination with our microarray data.
Dr. Kandouz received his Ph.D. from Paris 7 University in France. He worked most recently as a Scientific Director of the WEBC cell imaging platform of the Segal Cancer Centre at McGill University. He is now starting an Assistant Professor tenure track position at the Department of Pathology at Wayne State University in Detroit. He is interested in the mechanisms of dysregulation of tissue homeostasis, particularly cell death and intercellular communication.
Who: Dr. Scott M. Kahn, Director of Basic Urologic Research
Institution: St. Luke’s-Roosevelt Institute for Health Sciences and Herbert Irving Comprehensive Cancer Center, Columbia University, USA
Product Highlight: SwitchGear Androgen Receptors
Our research focuses on the intracellular function of sex hormone-binding globulin (SHBG), a steroid binding protein expressed within the prostate. To better understand epidemiologic and genetic findings implicating SHBG in prostate cancer, we are investigating how locally synthesized SHBG modulates androgen signaling and androgen receptor (AR) activation in prostate cells.
We hypothesize that prostate tumors adapt to androgen ablation by altering SHBG SwitchGear’s Androgen Receptor Panel will enable us to 1) confirm SHBG modulates FKBP5 expression, and 2) ascertain whether SHBG selectively affects known androgen-responsive promoters SHBG, thus revealing functional targets.
Dr. Kahn has a long and deep interest in personalized medicine and pursuing a Rosetta stone for tumors that will enable clinicians to individualize cancer patient care. In addition to his current research on the role of locally expressed sex hormone-binding globulin in prostate and breast cancer, Dr. Kahn has published on the microsatellite mutator phenotype, cyclin D1 gene amplification and function in human cancer, protein kinase C signaling, and he has invented assays for biomarker detection.
Dr. Kahn obtained his Ph.D. from SUNY @ Stony Brook, and performed his postdoctoral work at Columbia University. He also spent time at the National Cancer Center in Tokyo, Japan as a visiting research scientist.
Who: Dr. Dina Bellizzi, Assistant Professor
Institution: University of Calabria, Italy
Product Highlight: SwitchGear Glucocorticoid Receptor Biomarker Set
We will investigate whether the presence/absence of the mitochondrial DNA influences the cellular response to glucocorticoid hormones by modulating the expression of nuclear genes through a cross-talk between mitochondrial and nuclear DNA. The SwitchGear reporter constructs from the Glucocorticoid Receptor Biomarker Set contain the promoters of genes which are specifically modulated by glucocorticoids. These constructs will be analyzed in both cells with functional mitochondria and in cells lacking functional mitochondrial because of depleted own mitochondrial DNA. We will test both the basal condition and the stimulation with glucocorticoids.
Dr. Bellizi is an Assistant Professor of Genetics working in the Department of Cell Biology at the University of Calabria (Italy). Her research is focused to disentangle the molecular basis of the cellular response to stress and to hormone stimulation. She extensively studied the variability of genes involved in stress response and the correlation of such a variability both with gene expression and with human phenotypes (aging and longevity). In the last year she carried out a research on apoptosis with a systems biology approach.
Who: Dr. Chao Zhao, Young Investigator
Institution: Shanghai Medical College, Fudan University, China
Product Highlight: SwitchGear Cholesterol Biosynthesis (SREBP) Biomarker Set
Hepatitis B virus (HBV) infection is known to play a role in liver disease and has been shown to disturb cholesterol biosynthesis in the liver. Specifically, HBsAg (an envelope protein of HBV) is secreted as lipoprotein particles in which cholesterol comprises ~15% of the lipid composition. We have found that diminished cholesterol synthesis inhibits HBsAg secretion in Hep3B and HepG2 cells. Also, we observed at least five genes of key enzymes in the metabolism pathways were differentially expressed in our HBV transgenic mouse model and/or HBsAg stably expression cell line.
To find out and confirm more candidates in the cholesterol biosynthesis pathway associated with HBV, we will co- transfect the HBsAg genes (3 distinct forms, large, middle and small HBsAg genes) with SwitchGear Cholesterol Biosynthesis (SREBP) Biomarkers (reporters). To further confirm the data, the stably HBsAg expression cell and its control cell would be analyzed using differentially expressed genes above. The objective of this application is to determine the candidates in cholesterol biosynthesis pathway associated with HBV, which would benefit preventive and therapeutic purposes of chronic HBV infection.
Dr. Zhao is a Young Investigator in a key lab of medical molecular virology at Shanghai Medical College, Fudan University. He focuses on the mechanism of the HBV chronic infection and the interaction between HBV and the host liver cell. Dr Zhao has published four first author articles two co-authored articles in this field. Dr. Zhao currently holds several grants for his research on the mechanism of the HBV chronic infection and its pathogenesis.
Who: Dr. Qiou Wei, Post Doctoral Fellow
Institution: National Cancer Institute, NIH, USA
Product Highlight: All SwitchGear Biomarker Sets (HIF1a, SREBP, STAT1, NF-Kb, CREB, p53, AR, ER, GR, and HSF)
Our previous study has demonstrated that Srx is required for neoplastic transformation and is highly expressed in human cancers (Wei et al PNAS 2008). However, the molecular signaling pathways by which Srx affects cancer cells have not been determined.
We have successfully established human lung cancer cells that are depleted or overexpressed with Srx by lentiviral based techniques. These cells have distinctive characters on the aspects of tumor maintenance, migration and invasion. To identify the downstream signaling pathways mediated by Srx that essentially contribute to these changes, we propose to use the selected biomarker sets to determine whether the loss or gain-of-function of Srx in human cancer cells affects certain particular signaling pathways. A comparison of the response between the knockdown and overexpressing cells will be extremely helpful for us to pinpoint the molecular mechanism by which Srx functions as a novel oncogene in the development of human lung cancers.
Dr. Wei completed his undergraduate/MD training at Chongqing Medical University (Chongqing, P.R. China) in 1994 and PhD at the University of South Dakota (Vermillion, SD) in 2005. He had served as a postdoctoral fellow in cell signaling at the Children’s Hospital Boston, Harvard Medical School for two years and currently is a CRTA postdoctoral fellow in the Lab of Cancer Prevention, National Cancer Institute at Frederick, National Institute of Health. He is passionate about studying the cellular and molecular aspects of tumorigenesis and cancer development using various models.
Who: Dr. Steven Gray, Senior Clinical Scientist and Lecturer
Institution: St James’s Hospital/Trinity College Dublin, Ireland
Product Highlight: SwitchGear NF-kB, Glucocorticoid Receptor, STAT1, Heat Shock Biomarker Sets
We are interested in the potential use of histone deacetylase inhibitors in the treatment of disease. We will use Switchgear technology to examine whether agonists/ antagonists of HDACs may have activity as an Adjunct Therapy to Interferon Treatment of Hepatitis C (HCV). The SwitchGear technology will help us gain a further understanding of the pathways underpinning interferon-alpha responses and to determine whether targeting HDACs either with agonists or antagonists will enhance interferon-alpha responses in our HCV model. Initially we propose to utilise the STAT1 biomarker set, but we envisage expanding these to include the NF-kB, Heat Shock (HSF) and the Glucocorticoid Receptor Biomarker Sets as these have all been shown to play important roles in oxidative stress, a condition associated with chronic HCV infection.
Dr Steven Gray graduated from Trinity College Dublin in 1992 and received his PhD in Molecular Biology from the Karolinska Institute Stockholm in 2000. He subsequently worked in research at the Van Andel Research Institute, Harvard Medical School, The German Cancer Research Centre (DKFZ) and the Hagedorn Research Institute, before returning to Ireland where he is a senior clinical scientist attached to St James’s Hospital.
Who: Dr. Rizwan Haq, Instructor of Medicine
Institution: Harvard Medical School, USA
Product Highlight: All SwitchGear Biomarker Sets (HIF1a, SREBP, STAT1, NF-Kb, CREB, p53, AR, ER, GR, and HSF)
We are interested in the molecular regulation of human pigmentation. As pigmentary responses such as tanning are required to protect from ultra-violet light and prevent melanoma, we have conducted a high-throughput chemical screen to identify non-carcinogenic ways of inducing human pigmentation.
Our high throughput screen has generated some lead compounds that induce pigmentary responses in human melanocytes. We hope to understand the pathways by which these small molecules induce these responses. The SwitchGear Pathway Biomarker Sets are critical to define which pathways are modulated by these drugs and to elucidate mechanisms which can be exploited for therapies to prevent melanoma.
Dr. Rizwan Haq completed his undergraduate, and MD/PhD training at the University of Toronto, Canada. He has served as a resident of internal medicine at Johns Hopkins Hospital and completed a fellowship in Medical Oncology at Dana-Farber Cancer Institute/Harvard Medical School. He is now a member of the Center for Melanoma, Massachusetts General Hospital at Harvard Medical School. In addition to seeing patients, he conducts research involving the signal transduction pathways regulating pigmentation.
Who: Dr. Bakhos Tannous, Assistant Professor and PI, and Dr. Christian E. Badr, Post Doctoral Fellow
Institution: Massachusetts General Hospital and Harvard Medical School, USA
Product Highlight: SwitchGear NF-kB, Heat Shock (HSF), p53, and Hypoxia (HIF1a) Biomarker Sets
We previously identified four drugs as sensitizers of primary glioblastoma cells to TRAIL-induced cell death both in vitro and in vivo through a cell-based functional drug screening assay. One of these drugs induces a caspase-independent necrotic-like cell death pathway with low mitochondrial membrane potential and early ATP depletion. The lab will use the SwitchGear NF-kB, Heat Shock (HSF), p53, and Hypoxia (HSF) Biomarker Sets to understand this alternative cell death pathway in tumor cells and a possible cross-talk with the TRAIL signaling pathway. We hypothesize that employing drugs that eliminate glioblastomas through a non-apoptotic cell death mechanism may be a useful strategy to circumvent resistance of cancer cells to apoptosis.
Dr. Tannous is an Assistant Professor of Neurology at the Harvard Medical School and a Research Associate in Neuroscience at the Massachusetts General Hospital. His research interests include developing molecular biosensors which report from tumor environments; targeting brain tumors using different gene transfer technologies; and high throughput screening for drugs which act specifically against brain tumor stem-like cells. Christian Badr is a post-doctoral fellow in Dr. Tannous laboratory working on drug screening and novel imaging modalites for brain tumors.