|
Dr. Mir Ahamed Hossain is a research scientist at the Kennedy Krieger Institute. He is also an Assistant Professor of Neurology at the Johns Hopkins University School of Medicine.
Biographical Sketch:
Dr. Hossain pursued his undergraduate and graduate education at the University of Calcutta, India, where he obtained his Ph.D. in Biochemistry in 1990. Dr. Hossain is a molecular/cellular biologist with considerable expertise in experimental neuroscience and neurotoxicity.He served as a research fellow in the University�s Department of Biochemistry before coming to the United States in 1990 for postdoctoral fellowships; first in the Department of Pharmacology at the University of Colorado and then in the Department of Neuroscience at the Johns Hopkins University School of Medicine and Department of Neurology at Kennedy Krieger Institute.
Dr. Hossain is a member of the American Society for Pharmacology and Experimental Therapeutics, the Society for Neuroscience. In 1984 he was awarded the Junior Research Fellow Scholarship by the Indian Government�s Indian Council of Medical Research.
Research Summary:
A major cause of neurodevelopmental handicaps in children is hypoxic/ischemic brain injury from perinatal anoxia and insufficient cerebral blood flow, resulting in major deficits in cognitive, sensory and motor disabilities for which currently there is no promising therapy. Brain injury initiated by hypoxic/ischemic insult results from a complex of events in which excitotoxicity plays a critical role. Excitatory amino acid such as glutamic acid, acting as both a neurotoxin and excitatory neurotransmitter, contributes to the pathogenesis of many forms of acute and chronic neuronal injury including hypoxia/ischemia, status epilepticus, trauma and neurodegenerative diseases such as Huntington�s and Parkinson�s disease. Lead (Pb) is a widespread environmental element which is also toxic to the nervous system. Lead toxicity constitutes a major medical issue worldwide and in numerous US cities such as Baltimore.
Over the past several years, the object of Dr. Hossain�s research has been on two different directions: (1) to understand the molecular and intracellular signaling mechanism(s) of neuroprotection and repair against neurotoxicity and hypoxic/ischemic brain injury within the central nervous system, and (2) to study molecular mechanisms of lead-induced cerebrovascular dysfunction and changes in intracellular second messenger signaling pathways and gene expression in central nervous system neurons.
In the first area, Dr. Hossain has established a novel endothelial cell-based method of delivering growth and neurotrophic factors gene into neonatal brain. He has found that delivery of acidic fibroblast growth factor (FGF-1) transgene dramatically reduces brain sensitivity to the neuropathological consequences of quinolinic acid, an endogenous excitatory amino acid (EAA) that plays a role in delayed neuronal death that follows cerebral ischemia. His present research focuses on the molecular events, the intracellular second messenger signaling pathways and the role of different transcription factors underlying the neuroprotective actions of growth and neurotrophic factors against excitotoxicity and hypoxic/ischemic brain injury using both in vitro primary neuronal cell culture and in vivo animal models. Dr. Hossain�s research will help to identify novel molecular targets that could become the basis for developing broadly applicable neuroprotective strategies for the treatment of hypoxic/ischemic brain injury and potentially neurodegenerative diseases.
In the second area, Dr. Hossain seeks to elucidate lead-induced gene expression changes at the blood-brain barrier and establishing their molecular/biochemical basis. His cDNA expression microarray analysis identified several lead-sensitive genes in astrocytes, of which vascular endothelial growth factor (VEGF) was one of the most sensitive. Subsequent experiments revealed that lead induces VEGF via PKC/AP-1-dependent and hypoxia inducible factor-1(HIF-1)-independent pathway. This is the first demonstration that lead induces gene expression of a growth factor, and the first detailed dissection of the second messenger pathways and transcription factors that mediate the effects of lead on gene expression in CNS cells. Dr. Hossain�s findings will help to identify lead�s cerebrovascular molecular targets and produce novel insights into general mechanisms by which lead disrupts brain function.
Recent Publications/Presentations:
Russell J.C., Szuflita N., Khatri R., Laterra, J and Hossain, M.A: Transgenic expression of human FGF-1 protects against hypoxic ischemic injury in perinatal brain through intervening at caspase-XIAP signaling cascades. Neurobiology of Disease, 22: 677-690, 2006.
Hossain M.A., Russell J.C., O�Brien R and Laterra J: Neuronal pentraxin 1: a novel mediator of hypoxic ischemic injury in neonatal brain. J. Neurosci., 24(17):4187-4196, 2004.
Hossain M.A., Russell J.C., Miknyoczki S., Ruggeri B., Lal B and Laterra J: Vascular endothelial growth factor mediates vasogenic edema in acute lead encephalopathy. Ann. Neurol. 55: 660-667, 2004.
Lou H.R., Hattori H., Hossain M.A., Hester L., Huang Y., Lee-Kwon W, Donowitz M., Nagata E and Snyder S.H: Akt as a mediator of cell death. PNAS (USA), 100 (20): 11712-11717, 2003.
Hossain M.A., Russell J.C., Gomez R. and Laterra J:Neuroprotection by scatter factor/hepatocyte growth factor and FGF-1 in cerebellar granule neurons is phosphatidylinositol 3-kinase/Akt-dependent and MAPK/CREB-independent. J. Neurochem., 81(2):365-378, 2002.
Hossain MA, Bouton CML, Pevsner J and Laterra J. Induction of vascular endothelial growth factor in human astrocytes by lead: Involvement of a protein kinase C/activator protein-1 complex-depednent and Hypoxia inducible factor 1-independent signaling pathway. J. Biol. Chem., 275: 27874-27882, 2000. | 