Samuel J. Black

Molecular basis for Control of African Trypanosomiasis and Equine Laminitis

Molecular Basis of Immunity against African trypanosomes (Collaboration with Stefan Magez, Free University of Brussels, Belgium, Terry Pearson , University of Victoria, Canada, and Jan Naessens, ILRI, Kenya) –

Our goal is to identify molecular interactions between mammal hosts and African trypanosomes that affect the development of protective immune responses as well as pathophysiologic processes. African trypanosomes are flagellated protozoa that cause sleeping sickness in people and Nagana in domestic animals. These diseases are fatal if left untreated. The diseases are endemic in the humid and semi-humid zones of Africa affecting a landmass of 10 million km 2 and 36 countries. Trypanosomiasis precludes cattle-based agriculture from much of this area and threatens up to 60 million people, of whom about a half million are presently infected. We are taking three approaches: (i) elucidating the protective responses that develop in Cape buffalo. These trypanosomiasis-resistant bovids co-evolved with African trypanosomes and efficiently suppress trypanosome parasitemia to a cryptic level upon infection. (ii) Elucidating the CD1d-restricted protective immune response that arises in mice that are vaccinated against the GPI anchor of the trypanosome variant surface glycoprotein, or infected with phospholipase C knock-out trypanosomes. (iii) Elucidating the contribution of TNF " , ADAM 17 (TACE) and TIMP3 to regulation of trypanosome-induced pathology

Control of inflammation in equine laminitis (collaboration with Jim Belknap, Ohio State University School of Veterinary Medicine) –

Our goal is to develop prophylactic therapies against equine laminitis. The digital laminae are composed of extracellular matrix and link the coffin bone of the foot to the hoof wall, thus suspending the horse’s weight within the hoof. Failure of the laminae results in severe lameness and affected horses are often euthanized. Our studies show that failure of the laminae is preceded by local elevated expression of the neutrophil chemoattractant IL-8, followed by recruitment of blood neutrophils which release matrix metalloproteinase 9 and oxygen radicals possibly causing laminar pathology. Current research is directed at further resolving pathophysiologic processes that lead to laminitis including, i) neutrophil and vascular endothelium interactions that result in extravasation of the inflammatory leukocytes, ii) the involvement of elastase, metalloproteinases of the ADAM and ADAM-TS families and their inhibitors (TIMPs) in breakdown of the laminar matrix, iii) the involvement of reactive oxygen and nitrogen species in loss of laminar integrity including fibroblast and basal epithelial cell hemidesmosome number and molecular constituents.