Mariangela Segre
Professor, Pathobiology
Director
of Undergraduate Studies, Pathobiology
Professional Interests: The study
of immunoregulation has been the primary interest of my lab for many
years. The following brief descriptions illustrate some of the ongoing
projects.
It is well documented that, in both mice and humans, the immune function deteriorates
with age. Some of our studies in mice point to a sequential degeneration of various
immune parameters. Our latest cross-sectional and longitudinal studies of Labrador
retrievers verified that the deterioration of the immune system also occurs in
aging dogs. Since dietary restriction in rodents has been found to prolong life-span
and delay the onset of age-related deterioration of physiologic systems including
the immune system, we are now engaged in a longitudinal study on the effect of
dietary restriction on various parameters of the immune system of Labrador retrievers.
The ubiquitous contaminants, polychlorinated biphenyls (PCBs), are known to have
a broad spectrum of biological effects especially on the developing organs. Their
effect on the immune system is insidious and difficult to reveal. To increase
the chances of uncovering even modest consequences of exposure, we studied the
immunological changes of wild mice pups exposed in utero and by lactation to
PCB. Current studies of inbred mice are designed to identify the cellular targets
and the strains mechanism(s) of the observed toxic effects.
The consequences of cocaine intake are due to accumulation of dopamine in the
synaptic junction. Cocaine binds to dopamine transporters and, in so doing, inhibits
re-uptake. We have established that anti-idiotypic antibodies, which mimic the
configuration of the cocaine molecule, can be used as an effective vaccine in
mice to generate cocaine-specific antibodies. Upon cocaine challenge, these antibodies
are effective in reducing the level of the drug reaching the brain. Recent literature
suggests that the cocaine binding-site on the dopamine transporter is distinct
from the dopamine-binding site and that the molecule of cocaine might play a
more active role than previously suspected. A molecule which binds the cocaine-binding
site on the transporters, but allows the re-uptake of dopamine could provide
an effective therapeutic alternative. Current studies look at the possibility
that the anti-idiotypic antibodies generated to mimic the configuration of cocaine
might be the source of peptides capable of fulfilling this role.
Lice are a major economic problem in cattle production across the United States.
The involvement of the immune system in the severe health deterioration caused
by infestation has never been proven. Studies designed to establish whether the
immune system is affected by such infestation and whether a vaccine can afford
protection are the subject of a collaborative effort in which our laboratory
is participating.
Selected Publications:
Arena SM, Greeley EH, Halbrook RS, Hansen LG and Segre M. 2002 Biological effects of gestational and lactational PCB exposure in neonatal and juvenile C57BL/6 mice. Archives of Environmental Contamination and Toxicology 44:272-280.
Segre M. 2003 Vulnerability of the developing immune system to environmental Polychlorinated Biphenyl contamination. in Recent Research Developments in Immunology, 5:237-254, Research Signpost, Kerala , India.
Ho M and M Segre. 2003 Inhibition of cocaine binding to the human dopamine transporter by a single chain anti-idiotypic antibody: its cloning, expression, and functional properties. Biochimica et Biophysica Acta 1638:257-266.
Greeley E, E Spitznagel D Lawler, R Kealy, M Segre. 2004 Modulation of canine immunosenescence by life-long caloric restriction. In preparation, to be submitted to Experimental Gerontology.
DE Hutchens, CJ Jones, AJ Paul, E Greeley, R Wallace, LF Firkins, TF Lock, R Singer, L Kohrt and M Segre. 2004 Linognathus vituli Population dynamics and immunological host response during repeated experimental infestations of both normal and stressed cattle. To be submitted to Veterinary Parasitology.
