Mark S. Kuhlenschmidt
Professor and Assistant Department Head, Pathobiology
Professor, Center for Zoonoses Research
Professional Interests: Microbial
adhesion, infectious diseases and complex carbohydrate biochemistry.
The
long-term goals of our research are to identify pathogenic mechanisms
responsible for infectious disease and to develop therapeutically effective
intervention strategies. Our early studies
focused on the initial recognition and adhesion events between the microbial
agent and host cell in an effort to identify microbial adhesion receptors. We
developed in vivo -simulating in vitro binding assays
that allowed quantification of physiologically-relevant microbial adhesion
as well as in vivo intestinal xenograft systems with which we
could test the therapeutic efficacy of identified receptors or receptor
analogues. Using this approach we identified a specific intestinal
ganglioside that function as a rotavirus receptor and is capable of blocking
both virus binding and infectivity of host cells in vitro and rotavirus shedding
and diarrhea in vivo. Based on these data, we are now involved in
collaborative basic and translational research studies aimed at identifying
and delivering naturally occurring or synthetic inhibitors of rotavirus
infectivity to both animals and people using a nutritional intervention
strategy. The results of these studies should lead to the development
of proven therapeutic drugs aimed at blocking either or both, the initial adhesive
event or subsequent propagation of the virus within its host cell. Using
a similar approach, we have also identified and purified a natural lipid
component from bovine intestine that blocks Cryptosporidium parvum (a
protozoan parasite often seen as an opportunistic pathogen in AIDS patients)
sporozoite binding to host cells. We are currently deciphering the
chemical nature and mechanism of action of this lipids and whether
it is effective as a feed supplement in reducing or eliminating Cryptosporidiosis in
a dairy calf animal model. In other collaborative studies, we are
attempting to reduce the environmental load of waterborne Cryptosporidium oocysts
from agricultural runoff. We have determined that the use of properly
developed vegetative filter strips (VFS) represents an on-farm, best
management practice for control of Cryptosporidium parvum runoff
and watershed protection. In these studies, we also have identified
the critical soil components, in association with particular types of
surface vegetation that are responsible for retention of Cryptosporidium
parvum oocysts within VFS. The combination of these multiple
prophylactic and therapeutic approaches should help reduce the incidence
and disease associated with these gastrointestinal pathogens.
Selected Publications:
Bergner DW, Kuhlenschmidt TB, Firkins LD and Kuhlenschmidt MS. (2005) Receptor Therapy for Porcine Rotavirus Disease: Characterization of a Neoglycolipid Carbomimetic that Blocks Virus Infectivity (submitted).
Wetzel DM, Schmidt J, Kuhlenschmidt MS, Dubey JP and Sibley LD. (2005) Gliding motility by Cryptosporidium parvum sporozoites relies on a conserved actin-myosin motor. Infection and Immunity . 73(9): 5379�5387.
Johnson JK, Schmidt J, Gelberg HB and Kuhlenschmidt MS. (2004) Microbial Adhesion of Cryptosporidium parvum sporozoites: Purification of an Inhibitory Lipid from Bovine Mucosa. J Parasitology. 90:980-990.
Trask J, Kalita PK, Kuhlenschmidt MS,
Smith RD and Funk TL. (2004) Overland and Near-surface Transport of Cryptosporidium
parvum. J Environ Qual. 33:983-993.
