Danny Manor, Ph.D.
Associate Professor
Phone:
(216) 368-6230
Fax:
(216) 368-6644
E-mail:
danny.manor@case.edu
Wood RT-600
BACKGROUND
Danny Manor completed his undergraduate studies in Biochemistry in 1982 at Tel Aviv
University in Israel. He received his PhD in Anatomy, Structural Biology and Biophysics
from the Albert Einstein College of Medicine, NY in 1989. He then then held a postodctoral
position in the Department of Physics at the City University of New York, where
he applied biophysical approaches for the study of visual pigments and GTP-binding
proteins. In 1992 Dr. Manor moved to the department of Pharmacology at Cornell University
in Ithaca NY, where he studied the role of small GTP-binding proteins in malignant
transformation. He then took a faculty position at Cornell's Division of Nutritional
Science, where his studies diversified to molecular bases of cancer prevention and
to vitamin E biology.
EDUCATION
B.Sc. (Biochemistry) 1982
Tel Aviv University (Israel)
Ph.D. (Anatomy, Structural Biology & Biophysics) 1989
Albert Einstein College of Medicine
(New York)
RECENT PUBLICATIONS
Qian J, Morley S, Wilson K, Nava P, Atkinson J, Manor D. (2005)
Intracellular trafficking of vitamin E in hepatocytes: Role of tocopherol transfer
protein. J Lipid Research, 46: 2072-82.
Kauppinen KP, Duan F, Wels JI, Manor D. (2005) Regulation of the
Dbl proto-oncogene by heat shock cognate 70 (Hsc70). J Biol Chem., 280: 21638.
Morley S, Curtis V, Cecchini M, Nava P, Atkinson J, Manor D. (2006)
Utility of a fluorescent vitamin E analog as a probe for tocopherol transfer protein
activity. Biochemistry, 45: 1075.
Qian J, Atkinson J, Manor D. (2006) Biochemical consequences of
heritable mutations in the alpha-tocopherol transfer protein. Biochemistry; 45:
8236-42.
Morley S, Wagner J, Kauppinnen K, Manor D (2007) Requirement for
Akt-mediated survival signaling in cell transformation by the dbl oncogene. Cell
Signal.; 19(1): 211-8.
Kamynina E, Kaupinnen K, Duan F, Muakkassa N, Manor D (2007) Regulation
of the proto-oncogeneic Dbl by ubiquitin-mediated proteasomal degradation. Molec.
Cell. Biol. 27: 1809-1822.
Manor, D & Morley, S. (2007) The hepatic tocopherol transfer protein.
Vitamins and Hormones 76: 45-65.
Valastyan, S., Thakur, V., Johnson, A. Kumar, K. & Manor D. (2008)
"Novel transcriptional activities of vitamin E: inhibition of cholesterol biosynthesis.
Biochemistry 47:744-52.
Morley, S., Cecchini M, Zhang, W., Virgulti, A., Noy, N., Atkinson, J. & Manor
D. (2008) Mechanisms of ligand transfer by the hepatic tocopherol transfer
protein". J. Biol. Chem. In press.
RESEARCH INTERESTS
My research team aims to gain molecular-level answers to basic questions that surround
the etiology, treatment and prevention of cancer. Our research interests can be
divided to two areas: (1) understanding the signal transduction pathways that regulate
normal cell growth and that are disrupted by oncogenic mutations, and, (2) understanding
the molecular mechanisms by which some chemo-preventative agents offer protection
from cancer ('molecular prevention').
Research Project I:
Signal transduction pathways that regulate cell growth
We are studying how proliferative signaling pathways are regulated in normal cells,
and how they are perturbed in particular cancers. We focus on the Dbl family of
proto-oncogenes that transduce signals from cell surface factors receptors to the
small GTP binding proteins Cdc42, Rac and Rho.
(1) How is the activity of proto-Dbl regulated in normal (untransformed)
cells?
The upstream events that lead to activation of Dbl- like exchange factors are unknown
at present. We seek to identify the molecules that functionally 'connect' between
the exchange factors and cell surface receptors, and how these regulate Dbl's biochemical
activity.
(2) What downstream pathway(s) and effectors contribute to Dbl
transformation?
Presently, little is known regarding how targets of small GTP-binding proteins
regulate cell growth (and transformation). We aim to delineate the downstream cascades
that respond to Dbl signaling, decipher their biochemical activity, and, most importantly,
understand their contribution to Dbl- induced transformation.
Research Project II:
Biological activities of vitamin E
Vitamin E (tocopherol) is a lipid soluble antioxidant that offers protection against
several 'oxidative stress'-related pathologies (cardiovascular disease, neuronal
degeneration, inflammation). Vitamin E supplementation also inhibits (and, to some
extent, reverses) tumor formation in animal cancer-models.
(1) What are the functions of vitamin E binding proteins?
Surprisingly little is known regarding intra-cellular targets with which vitamin
E interacts. We are studying the tocopherol transfer protein (TTP), which is mutated
in ataxia with vitamin E deficiency (AVED) patients. Using in vitro and
in vivo approaches, we aim to understand how TTP functions in order to
gain insights into its biological role(s) and, in turn, into the mode(s) of action
of vitamin E
(2) Are there antioxidant independent functions for vitamin E?
A few lines of evidence suggest that the physiological functions of vitamin
E involve activities that are independent of its anti-oxidant function, such as
stimulation of signaling cascades and modulation of transcriptional events. We aim
to characterize the genomic and metabolic activities of vitamin E, utilizing expression-
profiling and cell-biological approaches.