Jahan Ara, PhD
Assistant Research Professor
Drexel University College of Medicine
My primary research focus is on ischemic injury and recovery mechanisms in perinatal hypoxia-ischemia. For the last seven years my research is aimed at elucidating the mechanisms of neuronal protection against hypoxic-ischemic brain injury. The ultimate goal of this research is to devise novel experimental therapies to treat brain injury and improve recovery of function in patients that sustain hypoxic-ischemic injury or stroke. My laboratory has developed and validated a clinically relevant piglet model of induced tolerance to hypoxia-ischemia and has demonstrated the protective efficacy of preconditioning against hypoxic-ischemic injury in newborn piglet brain. I also demonstrated that hypoxic-preconditioning leading to tolerance to hypoxiaischemia in neonatal brain increased the expression of vascular endothelial growth factor (VEGF) and its receptors and investigated the molecular mechanisms of VEGF-signaling pathways in mediating neuroprotection and neurogenesis against hypoxic-ischemic injury. Currently, I am evaluating the effects of recombinant human VEGF on neuroprotection, angiogenesis, neurogenesis and behavioral outcomes in newborn piglets following hypoxic-ischemic brain injury.
In my laboratory, we also employ in vitro model system, the piglet subventricular zone (SVZ) neural stem/progenitor cell culture model, to study the regeneration and repair of newborn brain following hypoxic-ischemic injury. We found that hypoxic-preconditioning significantly increased the output of newly generated neurons and glial cells from SVZ, white matter, and striatum. As mechanisms regulating preconditioning-induced neurogenesis are only partially understood, my studies focus on determining whether moderate hypoxia or a severe hypoxia-ischemia subsequent to preconditioning could stimulate generation of functional neurons in the brain that migrate toward sites of damage, survive, and integrate into residual networks.
Neonatal hypoxia; neurodegeneration
- Ara, J., and De Montpellier, S. (2013). Hypoxic-preconditioning enhances the regenerative capacity of neural stem/progenitors in subventricular zone of newborn piglet brain. Stem Cell Research, 11 (2): 669686.
- Ara, J., Frank, M., and Shukla, P. (2013). Enhanced expression of the Flt-1 and Flk-1 receptor tyrosine kinases in a newborn piglet model of ischemic tolerance. J Neurochem., 124 (5): 735-746.
- de Chadarvian, JP, Legido, A, Halligan, GE, Faerber, EN, Piatt, JH, Morrissette, JD, Ara, J, Grant, ML, Katsetos, CD. (2011). Cerebellar Gliomatosis in a Toddler: Case Report of a Challenging Condition and Review of the literature. Journal of Child Neurology, 27: 511-520.
- Ara, J., Fekete, S., Frank, M., Golden, J. A., Pleasure, D., and Valencia, I. (2011) ""Hypoxic-preconditioning induces neuroprotection against hypoxia-ischemia in newborn piglet brain. Neurobiology of Disease, 43: 473485.
- Ara, J., Fekete, S., Zhu, A., Frank, M. (2010). Characterization of neural stem/progenitor cells expressing VEGF and its receptors in the subventricular zone of newborn piglet brain. Neurochem Res., 35 (9): 1455-1470.
- Bannerman, P., Ara, J., Hahn, A., Hong, L., McCauley, E., Friesen, K., and Pleasure, D. (2008): Peripheral nerve regeneration is delayed in neuropilin 2-deficient mice. J. Neurosci Res., 86 (14): 3163-3169.
- Delivoria-Papadopoulos M., Ashraf, Q.M, Ara, J. and Mishra O.P. (2008). Nuclear mechanisms of hypoxic cerebral injury in newborn: The role of caspases. Semin Perinatol., 32: 334-343.
- Ara, J., See, J., Mamontov, P., Hahn, A., Bannerman, P., Pleasure, D., and Grinspan, J. (2008). Bone morphogenetic proteins 4, 6 and 7 are upregulated in mouse spinal cord during experimental autoimmune encephalomyelitis. J Neurosci Res., 86: 125-135.
- Chiang, M.C., Ashraf, Q.M., Ara, J., Mishra, O.P., and Delivoria-Papadopoulos, M. (2007). Mechanism of caspase-3 activation during hypoxia in the cerebral cortex of newborn piglets. Neurosci Lett., 421: 67-71.
- Ara, J., Bannerman, P., Shaheen, F., and Pleasure D. (2005). A Schwann cell-autonomous role of neuropilin-2. J Neurosci Res., 79 (4): 468-475.
- Ara, J., Bannerman, P., Hahn, A., Ramirez, S., and Pleasure, D. (2004). Modulation of sciatic nerve expression of class 3 semaphorins by nerve injury. Neurochem Res., 29 (6): 1147-1153.
- Scarlato, M., Ara, J., Bannerman, P., Scherer, S., and Pleasure, D. (2003). Induction of neuropilins-1 and -2 and their ligands, Sema3A, Sema3F, and VEGF, during Wallerian degeneration in the peripheral nervous system. Exp Neurol.,183 (2): 489-98.
- Pleasure D., Bannerman P., Ara J., Scarlato M., and Itoh T. (2002). Prospects for vascular endothelial growth factor neurotherapeutics. Arch Neurol., 59 (5): 692-694.
- Souza, JM., Choi, I., Chen Q., Weisse, M., Daikhin, E., Yudkoff, M., Obin, M., Ara, J., Horwitz, J., and Ischiropoulos, H. (2000). Proteolytic degradation of tyrosine nitrated proteins. Arch. Biochem. Biophys., 380 (2): 360-366.
- Ara, J., Przedborski, S., Naini A.B., Jackson-Lewis, V., Horwitz, J and Ischiropoulos, H. (1998). Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Proc. Natl. Acad. Sci. USA., 95: 7659-7663.
- Ara, J., Gans, Z., Sweeney, R. and Wolf, B. (1995). A dot-ELISA for the rapid detection of gentamicin in milk. J. Clin. Lab. Anal., 9: 320-324.
- Ara, J. and Ali, R. (1995). Antigenic specificity of anti-ROS DNA antibodies: Involvement of lysyl residues in antigen binding. Biochem. Mol. Biol. Int., 35: 213-222.
- Ara, J. and Ali, R. (1993). Polynucleotide specificity of anti-reactive oxygen species (ROS) DNA antibodies. Clin. Exp. Immunol., 94: 134-139.
- Ara, J. and Ali R. (1993). Assay of antinuclear antibodies by ELISA using nuclei as antigen. Eur. J. Clin. Chem. Clin. Biochem., 31: 289-293.
- Ara, J. and Ali, R. (1992). Reactive oxygen species modified DNA fragments of varying size are preferred antigen for human anti-DNA autoantibodies. Immunol. Lett., 34: 195-200.
- Ara, J., Ali, A. and Ali, R. (1992). Antibodies against free radical modified native DNA recognize B-conformation. Immunol. Invest., 21: 553-563.