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COBRE RESEARCH SEMINAR SERIES
Taking a Tryp with its Twists and Turns
Across the Blood-Brain Barrier
Human African trypanosomiasis (HAT; commonly called sleeping sickness) has been claimed to be more deadly
than other vector-borne diseases such as malaria because death is inevitable if a patient is untreated. The
terminal stages of human sleeping sickness are characterized by neurologic signs, progressive coma, seizures
and a marked increase in nighttime insomnia and daytime drowsiness (from which the disease gets its name).
Sleeping sickness is caused by two subspecies of African trypanosomes (Trypanosoma brucei rhodesiense and
T. b. gambiense causing East African and West African sleeping sickness respectively). In classical late stage
human sleeping sickness the parasites invade the central nervous system (CNS) and the infected individuals
suffer from progressive neurologic involvement with concomitant psychiatric disorders and, if untreated, death.
Once inside the brain the parasites are shielded from many of the most effective trypanocidal drugs. Indeed, the
brain is probably the source for many relapse infections.
When this work was started in 2002, there was a general appreciation that in late stage HAT, a major factor in
pathogenesis was the ability of the trypanosome to cross the blood-brain barrier (BBB) and enter the CNS. At that
time, very little was known about how trypanosomes achieve passage across the functional unit of the BBB
comprised of human brain. In this talk, a review of our progress to delineate the mechanism of African
trypanosome traversal across the human BBB at the molecular and cellular levels with the hope that this research
that will lead to better therapies against the disease caused by this deadly parasite.
Dennis Grab, Ph.D.
Associate Professor
Department of Pediatrics, Division of Infectious Diseases
Johns Hopkins University School of Medicine
Baltimore, Maryland
Wednesday, July 11, 2012 at 10:15 a.m.
John A. Burns School of Medicine, Kaka‘ako
Medical Education Building Auditorium (Room 315)
For further information, call 692-1654
The Center and its activities are supported by a grant (P20GM103516) from the
National Institute of General Medical Sciences, National Institutes of Health.