Host-Pathogen  Interaction Laboratory
© 2015 - 2016 Uzonna (Created by F. Khadem)
Parasitic Disease Research Parasitic   diseases   continue   to   be   one   of   the   major   causes   of mortality    and    morbidity    around    the    world    (particularly    in developing   countries)   and   afflict   more   people   than   any   other infectious    disease.    Sadly,    despite    the    high    mortality    and morbidity   and   enormous   socio-economic   impact   of   parasitic diseases,   not   much   interest   is   shown   in   this   area   of   research and   parasitic   diseases   remain   relatively   neglected   in   terms   of research   investment.   At   Dr.   Uzonna’s   laboratory,   we   study two     diseases     caused     by     protozoan     parasites     namely: Leishmaniasis  and African trypanosomiasis . We   utilize   cellular   and   molecular   immunologic   approaches   to study   host-pathogen   interactions   that   result   in   susceptibility or   resistance   to   these   diseases.      We   have   taken   this   two- prong   (host   and   pathogen)   approach   because   we   believe   "it takes    two    to    tango"    and    that    the    outcome    of    infection    is influenced   by   the   intricate   interactions   between   the   host   and the    pathogen.        The    overarching    question    that    we    seek answer to is: “what      host      and      parasite      factors      contribute      to susceptibility     or     resistance     following     infection     with Leishmania or African Trypanosome?” Two     major     host     factors     of     particular     interest     to     our laboratory   are   regulatory   T   cells   and   memory   T   cells.   Some   of the questions we ask are: Do      memory      cells      develop      after      infection      with protozoan     parasites?          If     they     do,     how     are     they generated     and     are     they     important     in     resistance following secondary exposure? What   causes   the   loss   of   acquired   immunity   in   animals that     effectively     controlled     their     primary     parasitic infection? How    can    regulatory    T    cells    be    activated    to    prevent immune    cell    hyper-activation    and    the    subsequent pathology associated with such activation? From    the    parasite's    side,    we    are    interested    in    parasite- derived factors that: Enhance      the      invasion      process            resulting      in establishment of infection Contribute to the take-over of host immune defenses Alter   the   host   immune   system   to   make   it   permissible for parasite proliferation (immunomodulation). We   utilize   a   variety   of   animal   models,   including   targeted   gene knockout   and   transgenic   mice,   genetically   modified   parasites, and    more    recently,    proteomics    to    dissect    cellular    immune responses    following    protozoan    infections.        Although    we primarily   use   mouse   models   in   our   studies,   we   are   working towards   finding   vaccines   for   humans   and   livestock.   Some   of our   vaccine   candidates   are   in   the   early/planning   stages   of conducting protection studies in non-human primates. If   you   are   interested   in   finding   a   cure   and/or   vaccines   against poverty-associated   and   neglected   diseases   of   the   developing world,   come   and   join   the   dynamic   and   enthusiastic   team   of trainees and researchers in Dr. Uzonna’s Lab.
Sepsis/Septic shock Research Another     important     research     activity     going     on     in     our laboratory    (Host-Pathogen    Interaction    Laboratory)    involves understanding the pathogenesis of Sepsis/Septic Shock   Sepsis    syndrome    (also    known    as    systemic    inflammatory response   associated   with   infection,   sepsis,   severe   sepsis,   and septic   shock)   is   a   condition   characterized   by   a   whole-body inflammatory     state     and     the     presence     of     a     known     or suspected bacteria, usually gram-negative organisms.  Sepsis     syndrome     and     septic     shock     are     common     and frequently   fatal   clinical   conditions   in   all   age   groups   and   are leading   causes   of   mortality   in   intensive   care   units,   particularly in   children   and   older   adults.   Therefore,   understanding   the pathogenesis    of    the    disease    is    an    important    step    towards designing      appropriate      clinical      interventions      both      for preventive and treatment purposes. We    have    successfully    developed    a    laboratory    model    of lipopolysaccharide-induced    acute    inflammation    leading    to septic   shock   in   mice.   We   have   also   developed   an   Escherichia coli-induced   model   of   inflammation   in   mice.   We   are   using both   models   to   interrogate   the   role   of   regulatory   T   cells,   a subset    of    T    cells    that    act    to    restrain    and/or    suppress excessive   immune   activation,   and   phosphoinositide   3-kinase (PI3K),   a   key   intracellular   signalling   enzyme,   in   ameliorating sepsis   and   acute   inflammatory   responses.   There   are   ongoing clinical     studies     aimed     at     expanding     autologous     human regulatory    T    cells    in    vitro ,    for    in    vivo     infusion    to    treat autoimmune    disorders.    We    envisage    situations    where    this could   also   be   done   for   the   management   of   sepsis   and   septic shock in patients.
R G