GEORGE
P. STUDZINSKI
Professor
• M.D.
1958 University of Glasgow
• Ph.D. 1962
University of Glasgow
Research Interests
• Induction
of differentiation of human leukemic cells by novel analogs
of 1,25-dihydroxyvitamin
D 3 , particularly in combination with
plant antioxidants.
• MAP kinase pathways in relation
to cell proliferation,
differentiation, and cell death by apoptosis
in leukemia cells.
• Control of the cell cycle in human cancer
cells.
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Current Research
Signaling of differentiation of human leukemia cells
With the ultimate goal
of improving the prevention and treatment of human myeloid leukemias, we
are investigating the molecular mechanisms that reverse the malignant behavior
of leukemia cells. This is primarily done using established leukemia cell
lines, which can be normalized by an exposure to several agents including
the physiologically active form of vitamin D, 1,25-dihydroxyvitamin D 3 (1,25D
3 ). We have previously shown that differentiation of human leukemia cells
HL60 results in a proliferative block that is due to the upregulation of
the expression of the Cdk inhibitor p27 Kip1. Current studies focus on the
mechanisms by which this upregulation takes place, and the relationship of
signaling by mitogen-activated protein kinases (MAPKs) to differentation
and cell cycle arrest. The mechanisms include the upregulation of the retinoblastoma
susceptibility protein (pRb), and its interaction with transcription factors
such as C/EBPß. Additional studies
focus on the reversal of resistance of leukemia cells to 1,25D 3 , and its
less calcemic analogs by plant antioxidants.
Translational Studies
To increase the translational value of our studies we have established collaborations
with clinicians who provide leukemic blood samples (following informed consent
of the patients) for parallel studies ex vivo .
Representative
Publications:
Studzinski, G.P. “Cell differentiation in vitro; model systems” in:
Encyclopedia of Life Sciences, MacMillan Press, London, 2001.
Studzinski, G.P. A Compact Compendium on Caspases. Cell Cycle, 2:160-161,
2003.
Studzinski, P.G., Harrison, J.S. The neuronal cyclin-dependent kinase 5 activator
p35Nck5a and Cdk5 activity in monocytic cells. Leukemia and Lymphoma, 44:235-240,
2003.
Danilenko, M., Wang, Q.,
Wang, X., Levy, J., Sharoni, Y., Studzinski, G.P. Carnosic acid potentiates
the antioxidant and prodifferentiation effects of 1a,25-dihydroxyvitamin
D 3 in leukemia cells, but does not promote elevation of basal levels of
intracellular calcium. Cancer Res., 63:1325-1332, 2003.
Wang, Q., Wang, X., Studzinski, G.P. The jun N-terminal kinase pathway enhances
signaling of monocytic differentiation of human leukemia cells induced by 1,25-dihydroxyvitamin
D 3 . J. Cellular Biochem., 89:1087-1101, 2003.
Wang, X., and Studzinski G.P. Kinase suppressor of RAS (KSR) amplifies the
differentiation signal provided by low concentrations 1,25-dihydroxyvitamin
D 3. J. Cellular Physiology, 198:333-342, 2004.
Weyts, F.A., Dhawan, P., Zhang, X., Bishop, J.E., Uskokovic, M.R., Ji, Y.,
Studzinski, G.P., Norman, A.W., and Christakos, S. Novel Gemini analogs of
1,25-dihydroxyvitamin D 3 with enhanced transcriptional activity. Biochem.
Pharmacol., 67:1327-1336, 2004.
Ji, Y., and Studzinski,
G.P. Retinoblastoma Protein and CCAAT/Enhancer-binding protein ß are required
for 1,25-dihydroxyvitamin D 3 -induced differentiation of HL60 Cells. Cancer
Res,. 64:370-377, 2004.
Chen, F., Wang, Q., Wang,
X., and Studzinski, G.P. Upregulation of Egr1 by 1,25-dihydroxyvitamin D
3 contributes to increased expression of p35 activator of Cdk5 and consequent
onset of the terminal phase of HL60 cell differentiation. Cancer Res., In
press, 2004.
