Faculty and Staff
Swapan Ray, Ph.D.
|Title:||Professor of Pathology, Microbiology & Immunology
|Department:||Pathology, Microbiology & Immunology
School of Medicine
Pathology, Microbiology & Immunology
Brookhaven National Laboratory, Upton, NY.
Ph.D. University of Calcutta, Calcutta, India.
The research interests of my laboratory include the understanding of the cellular and molecular mechanisms of pathogenesis of malignant diseases such as glioblastoma, neuroblastoma, and Ewing's sarcoma and also neurodegenerative disorders such as spinal cord injury (SCI), brain ischemia, traumatic brain injury (TBI), Alzheimer's disease (AD), amyotropic lateral sclerosis (ALS), epilepsy, glaucoma, Parkinson's disease (PD), and multiple sclerosis (MS) and development of novel therapeutic strategies for their treatments. At present, we are primarily focusing our studies on the following projects:
Glioblastoma growth, angiogenesis, and apoptosis (Supported by the NCI grant R01 CA-91460):
The most malignant and prevalent brain tumor in humans is glioblastoma, which is composed of immature and abnormal cells of astroglial origin. Conventional treatment strategies do not address the inherent growth potential of glioblastoma cells and therefore fail to cure the patients. Prognosis of glioblastoma is extremely poor and as such glioblastoma is considered to be a death sentence because the patients usually do not survive more than a few months following diagnosis. Our studies focus on the understanding of the complex mechanisms of growth and angiogenesis in glioblastoma using the cell culture and animal (ectopic xenograft and orthotopic allograft) models of glioblastoma. We use retinoid, interferon-gamma, and nanoparticle-paclitaxel for chemoinnumotherapy (induction of MHC class II components) and combination chemotherapy to combat glioblastoma growth and angiogenesis and also activate proteolytic cascades for apoptosis.
Neuroblastoma cell cycle, differentiation, and apoptosis (Supported by the NINDS grant R01 NS-57811):
Neuroblastoma is an enigmatic childhood malignancy that is characterized by uncontrolled proliferation and lack of both differentiation and apoptosis in immature neuroblasts. The growth of malignant neuroblastoma in children over one-year age is hard to control with the currently available treatment strategies. Thus, there is an urgent need to explore innovative therapeutic strategies to control abnormal cell signaling and induce differentiation and apoptosis in neuroblastoma. Our research is focused on exploring the molecular basis of therapeutic actions of the combination of fenretinide and flavonoid for controlling cell proliferation and inducing differentiation and apoptosis in cell culture and animal (ectopic xenograft and orthotopic xenograft) models of human neuroblastoma.
Spinal cord injury pathogenesis, proteolytic cascades, and therapeutic strategies (Supported by the NINDS grant R01 NS-31622 and the State of SC grants SCIRF-607 and SCIRF-803):
Spinal cord injury (SCI) is a devastating and progressive neurological problem that mostly affects young population. Still there is no effective therapy for successful treatment of SCI patients who suffer a lot during their lifetime and ultimately die within a few years. The pathogenesis of SCI is complex. Our studies are designed to examine the evolution of complex pathological mechanisms such as inflammation, astrogliosis, microgliosis, Ca2+ influx, activation of proteolytic cascades, neurodegeneration, and lack of motor function in the Sprague-Dawley rat model of SCI. We use calpain inhibitors, estrogen receptor agonists, and also melatonin for the management of devastating consequences of SCI in acute and chronic SCI rats. Different components of this SCI project are carried out in our laboratory in collaboration with Drs. N. Banik and A. Varma.
Demyelination and neurodegeneration in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) and therapeutic strategy (Supported by the NINDS grants R01 NS-41088 and R01 NS-56176):
MS, which mostly affects women, is an autoimmune demyelinating disease in which the myelin and myelin-producing oligodendrocytes become the targets of T cell mediated autoimmune response, resulting in depletion of the white matter, increase in axonal damage, and deterioration of neuronal function. The strong support for considering MS as an autoimmune demyelinating disease comes from the studies on EAE, an animal model of MS. Currently, MS is also considered as a neurodegenerative disease. Our studies using EAE Lewis rats and human MS samples strongly suggest that upregulation of calpain contributes to demyelination and neurodegeneration. Therefore, we examine calpain inhibition as a potential therapeutic strategy for prevention of both demyelination and neurodegeneration in EAE animals. This research is performed in our laboratory in collaboration with Dr. N. Banik.
- Das A, Banik NL, Ray SK. Modulatory effects of acetazolomide and dexamethasone on temozolomide mediated apoptosis in human glioblastoma T98G and U87MG cells. Cancer Invest 26:352-358, 2008.
- Janardhanan R, Banik NL, Ray SK. N-(4-Hydroxyphenyl)retinamide induced differentiation with repression of telomerase and cell cycle to increase interferon-gamma sensitivity for apoptosis in human glioblastoma cells. Cancer Lett 261:26-36, 2008.
- Karmakar S, Banik NL, Ray SK. Combination of all-trans retinoic acid and paclitaxel-induced differentiation and apoptosis in human glioblastoma U87MG xenografts in nude mice. Cancer 112:596-607, 2008.
- Samantaray S, Sribnick EA, Das A, Knaryan VH, Matzelle DD, Yallapragada AV, Reiter RJ, Ray SK, Banik NL. Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats. J Pineal Res 4:348-357, 2008.
- Samantaray S, Knaryan VH, Butler JT, Ray SK, Banik NL. Spinal cord degeneration in C57BL/6N mice following induction of experimental parkinsonism with MPTP. J Neurochem 104:1309-1320, 2008.
- Das A, Banik NL, Ray SK. Retinoids induced astrocytic differentiation with down regulation of telomerase activity and enhanced sensitivity to taxol for apoptosis in human glioblastoma T98G and U87MG cells. J Neurooncol 87:9-22, 2008.
- Imam SA, Guyton MK, Haque A, Vandenbark A, Tyor WR, Ray SK, Banik NL. Increased calpain correlates with Th1 cytokine profile in PBMCs from MS patients. J Neuroimmunol 190:139-145, 2007.
- Karmakar S, Banik NL, Patel SJ, Ray SK. Combination of all-trans retinoic acid and taxol regressed glioblastoma T98G xenografts in nude mice. Apoptosis 12:2077-2087, 2007.
- Karmakar S, Olive MF, Banik NL, Ray SK. Intracranial stereotaxic cannulation for development of orthotopic glioblastoma allograft in Sprague-Dawley rats and histoimmunopathological characterization of the brain tumor. Neurochem Res 32:2235-2242, 2007.
- Das A, Banik NL, Ray SK. Differentiation decreased telomerase activity in rat glioblastoma C6 cells and increased sensitivity to IFN-gamma and taxol for apoptosis. Neurochem Res 32:2167-83, 2007.
- Sribnick EA, Matzelle DD, Banik NL, Ray SK. Direct evidence for calpain involvement in apoptotic death of neurons in spinal cord injury in rats and neuroprotection with calpain inhibitor. Neurochem Res 32:2210-2216, 2007.
- Das A, Banik NL, Ray SK. Garlic compounds generate reactive oxygen species leading to activation of stress kinases and cysteine proteases for apoptosis in human glioblastoma T98G and U87MG cells. Cancer 110:1083-1095, 2007.
- Zhang R, Banik NL, Ray SK. Combination of all-trans retinoic acid and interferon-gamma suppressed PI3K/Akt survival pathway in glioblastoma T98G cells whereas NF-kappaB survival signaling in glioblastoma U87MG cells for induction of apoptosis. Neurochem Res 32:2194-2202, 2007.
- Samantaray S, Knaryan VH, Guyton MK, Matzelle DD, Ray SK, Banik NL. The parkinsonian neurotoxin rotenone activates calpain and caspase-3 leading to motoneuron degeneration in spinal cord of Lewis rats. Neuroscience 146:741-755, 2007.
- Karmakar S, Banik NL, Patel SJ, Ray SK. 5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Neurosci Lett 415:242-247, 2007.
- Karmakar S, Banik NL, Patel SJ, Ray SK. Garlic compounds induced calpain and intrinsic caspase cascade for apoptosis in human malignant neuroblastoma SH-SY5Y cells. Apoptosis 12:671-684, 2007.
- Haque A, Das A, Hajiaghamohseni LM, Younger A, Banik NL, Ray SK. Induction of apoptosis and immune response by all-trans retinoic acid plus interferon-gamma in human malignant glioblastoma T98G and U87MG cells. Cancer Immunol Immunother 56:615-625, 2007.
- Ray SK. Currently evaluated calpain and caspase inhibitors for neuroprotection in experimental brain ischemia. Curr Med Chem 13:3425-3440, 2006.
- Das A, Banik NL, Ray SK. Mechanism of apoptosis with the involvement of calpain and caspase cascades in human malignant neuroblastoma SH-SY5Y cells exposed to flavonoids. Int J Cancer 119:2575-2585, 2006.
- Karmakar S, Banik NL, Patel SJ, Ray SK. Curcumin activated both receptor-mediated and mitochondria-mediated proteolytic pathways for apoptosis in human glioblastoma T98G cells. Neurosci Lett. 407:53-58, 2006.
- Sribnick EA, Matzelle DD, Ray SK, Banik NL. Estrogen treatment of spinal cord injury attenuates calpain activation and apoptosis. J Neurosci Res 84:1064-1075, 2006.
- Karmakar S, Weinberg MS, Banik NL, Patel SJ, Ray SK. Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane. Neuroscience 141:1265-1280, 2006.
- Das A, Garner DP, Del Re AM, Woodward JJ, Kumar DM, Agarwal N, Banik NL, Ray SK. Calpeptin provides functional neuroprotection to rat retinal ganglion cells following Ca2+ influx. Brain Res 1084:146-157, 2006.
- Ray SK, Karmakar S, Nowak MW, Banik NL. Inhibition of calpain and caspase-3 prevented apoptosis and preserved electrophysiological properties of voltage-gated and ligand-gated ion channels in rat primary cortical neurons exposed to glutamate. Neuroscience 139:577-595, 2006.
- Sribnick EA, Ray SK, Banik NL. Estrogen prevents glutamate-induced apoptosis in C6 glioma cells by a receptor-mediated mechanism. Neuroscience 137:197-209, 2006.