Isa M. Hussaini, Ph.D.
Isa M. Hussaini, Ph.D. Faculty Profile
Isa M. Hussaini, Ph.D.
Associate Professor of Pathology and
The prognosis for patients with malignant astroglial tumors is poor.
The capacity of astrocytomas both to invade adjacent brain sites and to
migrate into distant ones precludes curative surgical resection; and
little progress has been made in designing adjuvant therapies that
significantly affect long-term survival. In order to formulate more
novel therapeutic strategies, it is essential to have a better
understanding of how the invasive growth of these tumors is
The primary interest of the laboratory is the regulation of LRP (low
density lipoprotein receptor-related protein) expression and function
in astrocytic tumor cells. LRP is an endocytic receptor involved in the
trafficking of a variety of protein/protein complexes that have
pathophysiologic relevance in the central nervous system, including
urokinase (uPA) and its receptor (uPAR), lipoprotein metabolites, and
activated alpha2-macroglobulin. Changes in LRP expression may regulate
the levels of modulators (uPA, uPAR and PAI-1) of migration/invasion
around the microenvironment of astrocytic tumors.
The second project in my laboratory focuses on understanding
differences in PKC-eta activation and expression between malignant vs.
non-neoplastic astrocytes and on the role of PKC-eta in the control of
cell proliferation and apoptosis. The regulation of cell proliferation
and apoptosis in malignant astrocytic tumors is undoubtedly complex;
however, we are investigating how PKC-eta regulation of these processes
may be exploited to provide an experimental system in which
proliferative or apoptotic phenotype may be selectively induced and
studied. We are also extrapolating some of our results in cultured
cells to glioblastoma animal models. We hypothesize that
pharmacological regulation of PKC-eta, in combination with drugs
targeting cellular migration, may present a new therapeutic paradigm
for these aggressive brain tumors.
- Hussaini, I.M., Karns, L.R., Griffith, V.,
Carpenter, J.E., Redpath, G.T., Sando, J.J. and VandenBerg, S.R.
(2000). Phorbol 12-myristate-13-acetate induces protein kinase
C-η-specific proliferative response in astrocytic tumor cells.
J. Biol. Chem. 275: 22348-22354.
- Goldfarb, A.N., Delehanty, L.L., Wang, D., Racke, F.K. and
Hussaini, I.M. (2001). Stromal inhibition of
megakaryocytic differentiation correlates with blockade of signaling by
PKC-ε and ERK/MAPK. J. Biol. Chem. 276:
- Hussaini, I.M., Carpenter, J.E., Redpath, G.T
Sando, J.J., Shaffrey, M.E. and VandenBerg, S.R (2002). Protein kinase
C-η regulates resistance to UV- and γ-Irradiation-induced apoptosis by
preventing caspase-9 cleavage in astrocytomas.
Neuro-Oncology 4(1): 9-13.
- Aeder, S.E., Martin P.M., Soh J-W. and Hussaini,
I.M. (2004) PKC-η Mediates Glioblastoma Cell Proliferation
Through the Akt and mTOR Signaling Pathways.
- Amos S, Martin PM, Polar GA, Parsons SJ, Hussaini
IM. (2005). Phorbol 12-myristate 13-acetate induces epidermal
growth factor receptor transactivation via protein kinase C delta/c-Src
pathways in glioblastoma cells. J. Biol.
- Amos, S, Redpath, GT, Polar, G, McPheson, R, Schiff D and
Hussaini IM (2006). Farnesylthiosalicylic Acid Induces
Caspase Activation and Apoptosis in Glioblastoma Cells.
Cell Death and Differentiation,
- Abdel-Fattah, R., Xiao, A., Bomgardner D., Clinton-Scott, P., Lopes
M-B. S. and Hussaini, I.M. (2006) Differential
Expression of HOX genes in Neoplastic and Non-neoplastic human
astrocytes. The Journal of Pathology.
- Martin PM, Aeder, SE, Chrestensen, AC, Sturgill, TW and
Hussaini IM (2007) Phorbol Ester Induced Rapamycin
Insensitive Cell Proliferation is Regulated by Protein Kinase C-η.
- Hussaini IM, Trotter, C, Zhao, Y, Abdel-Fattah R,
Amos, S, Xiao, A, Agi CU, Redpath, GT, Fang Z, Gilberto LKK, Lopes BS,
Laws ER (2007) Differential Invasion-associated DNA Microarray Gene
Expression Profiles in Non-functioning Pituitary Adenomas: The Role of
MMP-9 in Pituitary Adenoma Invasion, Am J
- Uht, RM, Martin, PP, Riggan AE and Hussaini IM
(2007) The Protein Kinase C-η Induces Proliferaion in Glioblastoma Cell
Lines trough an ERK/Elk-1 Pathway Oncogene,
- Amos, S., diPierro CG, Carpenter, JE, Xiao, A, Kohutek,
Z, Redpath, GT, Zhao, Y, Wang, J, Mut, M, Shaffrey ME
and Hussaini, IM (2007) Protein Kinase C-α -mediated
regulation of Low Density Lipoprotein Receptor Related Protein and
urokinase increases Astrocytoma Invasion. Cancer
Research 67: 10241-10251.
- Zhao Y, Xiao A, Dipierro CG, Abdel-Fattah R, Amos S, Redpath GT,
Carpenter JE, Pieper RO, Hussaini IM. (2008) H-Ras
increases urokinase expression and cell invasion in genetically
modified human astrocytes through Ras/Raf/MEK signaling pathway.
- Li Y, Guessous F, Kwon S, Kumar M, Ibidapo O, Fuller L, Johnson E,
Lal B, Hussaini I, Bao Y, Laterra J, Schiff D,
Abounader R (2008) PTEN has tumor-promoting properties in the setting
of gain-of-function p53 mutations. Cancer