Education

PhD (Biochemistry)
University of Calcutta, Calcutta, India.
Postdoctoral Fellowship
Brookhaven National Laboratory, Upton, NY.

Research Interests

My research interests include both prokaryotic and eukaryotic molecular biology studies that relate to human health and diseases. Earlier in my career in prokaryotic molecular biology, I conducted research in a specific area of food microbiology for isolating, purifying, and discovering a plasmid (pSMB74) and its curing as well as conjugal transfer for linking its ability for production of a bacteriocin and immunity in a strain of Pediococcus acidilactici. Then, I moved to eukaryotic molecular biology to work as a Postdoctoral Fellow with the world-renowned late Biochemist Betsy M. Sutherland, PhD, and conducted research on mechanisms of ultraviolet light induced DNA damage and repair in human skin fibroblasts and human skin tissues at the Brookhaven National Laboratory (Upton, NY), one of the Associated Universities Inc. (AUI), in collaboration with a research group of Photomedicine Laboratory at the Harvard Medical School (Boston, MA). Subsequently, I took an interest in the mechanisms of induction of apoptosis, also known as programmed cell death, in human leukemia and breast cancer cells after treatments with standard and experimental therapeutic agents at Medical University of South Carolina (MUSC, Charleston, SC) and Winship Cancer Center at Emory University (Atlanta, GA).

I developed a sensitive method for isolation and detection of internucleosomal DNA fragmentation (a hallmark of apoptosis) in low number of human acute myeloid leukemia cells following therapeutic treatments, discovered that transfection of the human pro-apoptotic Bcl-xS gene using a mammalian expression plasmid vector induced erythrocytic differentiation and enhanced efficacy of differentiating agents in human chronic myeloid leukemia cells, invented an in situ method for simultaneous detection of apoptotic DNA fragmentation in a specific cell type in the tissue sections, created both non-radioactive and radioactive versions of the polymerase chain reaction (PCR) based telomerase assay for increasing its sensitivity and processivity, established for the first time that the Ca²⁺-dependent cysteine proteases in addition to the Ca²⁺-independent cysteine proteases participated in induction of apoptosis in the central nervous system (CNS) cells, proved preservation of electrophysiological functions of the neurons in vitro and recovery of neurological functions in vivo following inhibition of cysteine proteases, and serendipitously for the first time found pathogenesis in the spinal cord, in addition to brain, in the animal models of Parkinson’s disease and involvement of calpain in this process. Ever since I started my graduate studies, I had an insatiable curiosity about the structure and functions of the human brain including its emergence property the mind (the most evolved complex system in our known universe), workings in the whole CNS, and mechanisms of pathogenesis in CNS disorders. I had a dream of getting involved in research to devise the targeted therapeutic strategies for the CNS disorders. My dream came true as I started my career as a junior faculty, and it continued persistently for the challenging CNS studies.

Current research interests in my laboratory at the University of South Carolina School of Medicine (Columbia, SC) include understanding of cellular and molecular mechanisms of pathogenesis in malignant diseases such as glioblastoma, neuroblastoma, and Ewing’s sarcoma and neurodegenerative disorders such as spinal cord injury (SCI), brain ischemia, traumatic brain injury (TBI), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), epilepsy, glaucoma, Parkinson’s disease (PD), and the demyelinating and neurodegenerative disease multiple sclerosis (MS) and development of novel therapeutic strategies for their treatments. My laboratory is now extensively investing interplay between apoptosis and autophagy and trying to modulate these cellular mechanisms for treating the CNS disorders. For my research, I received grants from Federal and State Governments, Private Foundations, and Institutional Funds. To make my research multidisciplinary and translational, I collaborate with other investigators (basic scientists and medical practitioners) at our university and other universities across the nation. I provide training to undergraduate, graduate, and medical students, postdoctoral fellows, and junior faculty.

In line with my research interests over the years, I edited 4 peer-reviewed journal issues (Neurochemical Research, volume 32, number 12, December 2007; CNS & Neurological Disorders-Drug Targets, volume 7, number 3, June 2008; Neuroimmunology and Neuroinflammation -Pathogenesis in Spinal Cord Injury (SCI) and Therapeutic Strategies, 2020); and Cells - Cell Death Mechanisms and Therapeutic Opportunities in Glioblastoma, 2024)  and 5 books (Handbook of Neurochemistry and Molecular Neurobiology - Brain and Spinal Cord Trauma, 2009, 3^rd Edition, Springer Nature, New York, NY; GLIOBLASTOMA - Molecular Mechanisms of Pathogenesis and Current Therapeutic Strategies, 2010, Springer Nature, New York, NY; NEUROBLASTOMA - Molecular Mechanisms and Therapeutic Interventions, 2019, Elsevier/Academic Press, New York, NY; Retinoid and Rexinoid Signaling - Methods and Protocols, 2019, in the Methods in Molecular Biology (MIMB) book series, volume 2019, Springer Nature/Humana Press, New York, NY; and Neuroprotection - Methods and Protocols, 2024, in the MIMB book series, volume 2761, Springer Nature/Humana Press, New York, NY).

Research activities in my laboratory involve understanding the cell death mechanisms (e.g., pyroptosis, apoptosis, necrosis, PANoptosis) and the cellular recycling and homeostasis mechanism autophagy with the most investigations on DNA (e.g., genome, epigenome, damage and repair, CRISPR-Cas gene editing), RNA (e.g., mRNA, siRNA, miRNA), and protein (expression and activity) and finding connections between gut microbiome and CNS diseases for devising effective therapeutic strategies, now focusing mainly on the following 6 projects:

Glioblastoma: The most malignant and prevalent brain tumor in humans is glioblastoma, which is composed of immature and abnormal cells of astroglial origin. Conventional treatments do not suppress the inherent growth potential of heterogenic glioblastoma cells as well as of glioblastoma stem cells (GSCs) and therefore treatments fail to cure the patients. Prognosis of glioblastoma is extremely poor and per se, glioblastoma is a death sentence. Most of the patients do not survive more than a few months following diagnosis. Our studies focus on the complex mechanisms of growth and angiogenesis in GSCs and glioblastoma cells in cell culture and animal (ectopic xenograft and orthotopic allograft) models. We use retinoid, interferon-gamma, and nanoparticle-paclitaxel for cheminnumotherapy (for induction of MHC class II components), flavonoids, siRNA and microRNA technologies, and combination therapy to combat glioblastoma growth and angiogenesis, inhibit autophagy (a cellular recycling and survival mechanism), and activate proteolytic cascades for induction of apoptosis.

Neuroblastoma: 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 of 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 retinoid (natural or synthetic), flavonoid, siRNA, microRNA, and combination therapy for inhibiting cell proliferation and autophagy flux and promoting differentiation and apoptosis in cell culture and animal (ectopic and orthotopic xenograft) models of human neuroblastoma.

Spinal cord injury (SCI): SCI is a devastating and progressive neurological problem that mostly affects the young population. There is still no effective therapy for successful treatment of SCI patients who suffer a lot during their lifetime and 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, blockage of basal autophagy, 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, melatonin, and microRNA antagonists and mimics for the management of devastating consequences of SCI in acute and chronic SCI rats.

Multiple sclerosis (MS): MS mostly affects women and 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 strongest support for considering MS as an autoimmune demyelinating disease comes from the studies on experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Now, MS is known to be neurodegenerative disease. Our studies in 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.

Alzheimer’s disease (AD): AD named after the German neuropathologist Dr. Alois Alzheimer is a neurodegenerative brain disorder manifested with formation of abnormal amyloid plaques and neurofibrillary tangles, killing nerve cells first in the hippocampus and later in the cerebral cortex, causing loss of connections between the nerve cells, gradually wiping out memory and thinking skills, and eventually causing dementia or obliterating the cognitive functioning of the AD patients to deter them to carry out the easiest tasks. Our objectives include use of cell culture and animal models of AD for unraveling new pathogenic mechanisms for therapeutic targeting with natural and synthetic retinoids as well as plant derived flavonoids to prevent gut dysbiosis (an imbalance in gut microbiome), inflammation, and apoptosis, promote autophagy for functional neuroprotection.

Parkinson’s disease (PD): PD, which is first described as a ‘shaking palsy’ by the English physician Dr. James Parkinson, is an ongoing neurodegenerative movement disorder of the CNS, especially of the brain with loss of its substantia nigra neurons that produce dopamine (a neurotransmitter required by the dopaminergic neurons for regulating motor function, and motivation), leading to onset of tremor, muscle rigidity, slowness in movement (bradykinesia), stiffness in the limbs or the trunk of the body, impaired balance, loss of smell, sleep dysfunction, mood disorders, excess salivation, and constipation. Our studies in cell culture and animal models of PD strongly indicate that pathogenesis in PD extends to spinal cord (extra-nigral neurodegeneration) and calpain plays a critical role in this process. We use pharmacological and plant derived flavonoids for prevention of proteolytic pathways causing neuronal apoptosis, inhibition of gut dysbiosis and inflammation, and promotion of autophagy for functional neuroprotection in PD.

Representative publications

• Ray SK, Kim WJ, Johnson MC, and Ray B (1989) Conjugal transfer of a plasmid encoding bacteriocin production and immunity in Pediococcus acidilactici. J Appl Microbiol 66: 393-399.
• Ray S, Ponnathpur V, Huang Y, Tang C, Mahoney M, Ibrado A, Bullock G, and Bhalla K (1994) 1-β-D-Arabinofuranosylcytosine-, mitoxantrone- and paclitaxel-induced apoptosis in HL-60 cells: improved method for detection of internucleosomal DNA fragmentation. Cancer Chemother Pharmacol 34: 365-371.
• Bullock G, Ray S, Reed J, Miyashita T, Ibrado AM, Huang Y, and Bhalla K (1995) Evidence against a direct role for the induction of c-jun expression in the mediation of drug-induced apoptosis in human acute leukemia cells. Clin Cancer Res 1: 559-564.
• Bennett PV, Gange RW, Hacham H, Hejmadi VS, Moran M, Ray S, and Sutherland BM (1996) Isolation of high-molecular-length DNA from human skin. BioTechniques 21: 458-462.
• Bullock G, Ray S, Reed JC, Krajewski S, Ibrado AM, Huang Y, and Bhalla K (1996) Intracellular metabolism of Ara-C and resulting DNA fragmentation and apoptosis in human AML cells possessing disparate levels of Bcl-2 protein. Leukemia 10: 1731-1740.
• Ray S, Bullock G, Nunez G, Tang C, Ibrado A, Huang Y, and Bhalla K (1996) Enforced expression of Bcl-xS induces differentiation and sensitizes chronic myelogenous leukemia-blast crisis K562 to 1-β-D-arabinofuranosylcytosine-mediated differentiation and apoptosis. Cell Growth Differen 7: 1617-1623.
• Huang Y, Ray S, Reed JC, Ibrado AM, Tang C, Nawabi A, and Bhalla K (1997) Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of breast cancer MCF-7 cells. Breast Cancer Res Treat 42: 73-81.
• Ray SK, Fidan M, Nowak MW, Wilford GG, Hogan EL, and Banik NL (2000) Oxidative stress and Ca²⁺influx upregulate calpain and induce apoptosis in neuronal PC12 cells. Brain Res 852: 326-334.
• Ray SK, Schaecher KE, Shields DC, Hogan EL, and Banik NL (2000) Combined TUNEL and double immunofluorescent labeling for detection of apoptotic mononuclear phagocytes in demyelinating disease. Brain Res Protoc 5: 305-311.
• Ray SK, Patel SJ, Welsh CT, Wilford GG, Hogan EL, and Banik NL (2002) Molecular evidence of apoptotic death in malignant brain tumors including glioblastoma multiforme: Upregulation of calpain and caspase-3. J Neurosci Res 69: 197-206.
• Ray SK, Dixon E, and Banik NL (2002) Molecular mechanisms in the pathogenesis of traumatic brain injury. Histol Histopathol 17: 1137-1152.
• Ray SK, Hogan EL, and Banik NL (2003) Calpain in the pathophysiology of spinal cord injury: Neuroprotection with calpain inhibitors. Brain Res Rev 42: 169-185.
• Das A, Banik NL, Patel SJ, and Ray SK (2004) Dexamethasone protected human glioblastoma U87MG cells from temozolomide induced apoptosis by maintaining Bax:Bcl-2 ratio and preventing proteolytic activities. Mol Cancer 3: 36 (pages 1-10).
• Ray SK, Karmakar S, Nowak MW, and Banik NL (2006) 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.
• Das A, Banik NL, and Ray SK (2006) Molecular mechanism of apoptosis with the involvement of proteolytic activities of calpain and caspases in human malignant neuroblastoma SH-SY5Y cells exposed to flavonoids. Int J Cancer 119: 2575-2585.
• Ray SK (2006) Currently evaluated calpain and caspase inhibitors in experimental brain ischemia. Curr Med Chem 13: 3425-3440.
• Karmakar S, Banik NL, Patel SJ, and Ray SK (2007) 5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human malignant glioblastoma U87MG cells. Neurosci Lett 415: 242-247.
• Das A, Banik NL, and Ray SK (2007) Garlic compounds generated 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.
• Karmakar S, Banik NL, Ray SK (2008) Combination of all-transretinoic acid and taxol induced differentiation and apoptosis in human glioblastoma U87MG xenografts in nude mice. Cancer 112: 596-607.
• Samantaray S, Knaryan VH, Butler J, Ray SK, Banik NL (2008) Spinal cord degeneration in C57BL/6N mice following induction of experimental parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J Neurochem 104: 1309-1320.
• Janardhanan R, Banik NL, Ray SK (2009) N-Myc down regulation induced differentiation, early cell cycle exit, and apoptosis in human malignant neuroblastoma cells having wild type or mutant p53. Biochem Pharmacol 78: 1105-1114.
• George J, Banik NL, Ray SK (2009) Combination of hTERT knockdown and interferon-γ treatment inhibited angiogenesis and tumor progression in glioblastoma. Clin Cancer Res 15: 7186-7195.
• George J, Banik NL, Ray SK (2009) Combination of taxol and Bcl-2 siRNA induces apoptosis in human glioblastoma U251MG cells and inhibits invasion, angiogenesis, and tumorigenesis. J Cell Mol Med 13: 4219-4228.
• George J, Banik NL, Ray SK (2010) Survivin knockdown and concurrent 4-HPR treatment controlled human glioblastoma in vitro and in vivo. Neuro-Oncol 12: 1088-1101.
• Yu F, Li J, Chen H, Ray S, Huang S, Zheng H, Ai W (2011) Kruppel-like factor 4 (KLF4) is required for maintenance of breast cancer stem cells and for cell migration and invasion. Oncogene 30: 2161-2172.
• Ray SK, Samantaray S, Smith JA, Matzelle DD, Das A, Banik NL (2011) Inhibition of cysteine proteases in acute and chronic spinal cord injury. Neurotherapeutics 8: 180-186.
• Mohan N, Banik NL, Ray SK (2011) Combination of N-(4-hydroxyphenyl) retinamide and apigenin suppressed starvation-induced autophagy and promoted apoptosis in malignant neuroblastoma cells. Neurosci Lett 502: 24-29.
• Chakrabarti M, Banik NL, Ray SK (2013) Photofrin based photodynamic therapy and miR-99a transfection inhibited FGFR3 and PI3K/Akt signaling mechanisms to control growth of human glioblastoma in vitro and in vivo. PLoS One 8:e55652.
• Mohan N, Ai W, Chakrabarti M, Banik NL, Ray SK (2013) KLF4 overexpression and apigenin treatment down regulated anti-apoptotic Bcl-2 proteins and matrix metalloproteinases to control growth of human malignant neuroblastoma SK-N-DZ and IMR-32 cells. Mol Oncol  7:464-474.
• Mohan N, Chakrabarti M, Banik NL, Ray SK (2013) Combination of LC3 shRNA plasmid transfection and genistein treatment inhibited autophagy and increased apoptosis in malignant neuroblastoma in cell culture and animal models. PLoS One 8:e78958.
• Chakrabarti M, McDonald AJ, Reed JW, Moss MA, Das BC, Ray SK (2016) Molecular signaling mechanisms of natural and synthetic retinoids for inhibition of pathogenesis in Alzheimer’s disease. J Alzheimers Dis 50:335-352.
• Chakrabarti M, Klionsky DJ, Ray SK (2016) miR-30e blocks autophagy and acts synergistically with proanthocyanidin for inhibition of AVEN and BIRC6 to increase apoptosis in glioblastoma stem cells and glioblastoma SNB19 cells. PLoS One 11:e0158537.
• Taylor MA, Das BC, Ray SK (2018) Targeting autophagy for combating chemoresistance and radioresistance in glioblastoma. Apoptosis 23:563-575.
• Dasgupta S, Ray SK (2019) Ceramide and sphingosine regulation of myelinogenesis: Targeting serine palmitoyltransferase using microRNA in multiple sclerosis. Int J Mol Sci 20:5031.
• Al-Sammarraie N, Ray SK (2021) Bone morphogenic protein signaling in spinal cord injury. Neuroimmunol Neuroinflammation 2021; 8:53-63.
• Al-Sammarraie N, Ray SK (2021) Applications of CRISPR-Cas9 technology to genome editing in glioblastoma multiforme. Cells 10: 2342.
• Manea A, Ray SK (2021) Regulation of autophagy as a therapeutic option in glioblastoma. Apoptosis 26: 574-599.
• Visintin R, Ray SK (2022) Specific microRNAs for modulation of autophagy in spinal cord injury. Brain Sci 12: 247.
• Visintin R, Ray SK (2022) Intersections of ubiquitin-proteosome system and autophagy in promoting growth of glioblastoma multiforme: challenges and opportunities. Cells 11: 4063.
• Al-Sammarraie N, Mahmood M, Ray SK (2023) Neuroprotective role of Noggin in spinal cord injury. Neural Regen Res 8: 492-496.
• Manea A, Ray SK (2023) Advanced bioinformatics analysis and genetic technologies for targeting autophagy in glioblastoma multiforme. Cells 12: 897.
• Ray SK (2024) TUNEL-n-DIFL method for detection and estimation of apoptosis specifically in neurons and glial cells in mixed culture and animal models of central nervous system diseases and injuries. Methods Mol Biol 2761: 1-26.
• Ray SK, Dasgupta S (2024) Chromatographic separation and quantitation of sphingolipids from the central nervous system or any other biological tissue. Methods Mol Biol 2761: 149-157.
• Muraleedharan A, Ray SK (2024) Epigallocatechin-3-gallate and genistein for decreasing gut dysbiosis, inhibiting inflammasomes, and aiding autophagy in Alzheimer’s disease. Brain Sci 14: 96.

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