Merkel's Home Page
Glenn J. Merkel, Ph.D.
Department of Microbiology & Immunology
Indiana University School of Medicine
Fort Wayne, IN 46805
The
view from our lab (We wish!)
Our research focuses on studies with pathogenic fungi and bacteria.
We are
currently investigating the interactions of Cryptococcus neoformans
with mammalian target cells. C. neoformans is an encapsulated
yeast that causes life
threatening infections in immunocompromised patients. Click HERE for
photomicrographs.
Our previous work has demonstrated that C.
neoformans specifically adheres to and is internalized by potential
target cells such as the mouse lung epithelial cell below. What is
shown is an electron micrograph of a section of a lung cell containing
a number of internalized yeasts.
(Merkel & Cunningham, 1992, J. Vet. Med. Mycol. 30, 115-121)
We have recently demonstrated that C. neoformans adheres to and
is internalized by a human lung epithelial cell line.
(Merkel, G.J. & B. Scofield. 1997. The in vitro interaction of Cryptococcus
neoformans with human lung epithelial cells. FEMS Immunol. Med.
Microbiol. 19: 203-213.)
Click to view the abstract.
Using this same human lung epithelial cell line we have recently
demonstrated that antigens secreted by C. neoformans inhibit
tumor necrosis factor-induced intercellular adhesion molecule-1
expression on these epithelial cells.
(Merkel, Glenn J. and Barbara A. Scofield. 2000. The effects of Cryptococcus
neoformans secreted antigens on tumor necrosis factor induced
intercellular adhesion molecule-1 expression on human lung epithelial
cells. FEMS Immunol. Med. Microbiol. 29: 329-332.) Click to view the abstract.
Another recent paper characterizes a monoclonal antibody to those
secreted antigens above that inhibit TNF-induced ICAM-1 expression.
(Merkel, G.J. & B.A. Scofield. 1999. An opsonizing monoclonal
antibody recognizing a
non-capsular epitope expressed on Cryptococcus neoformans.
Infection & Immunity 67: 4994-5000.) Click here to view the abstract.
This monoclonal antibody (mAb) is interesting because it is the first
one described that reacts with a secreted, non-capsular epitope and
also opsonizes the yeasts making them more readily phagocytized. The
attached micrographs show mouse phagocytes
(click to view) and yeasts in the absence and presence of the mAb. Note
few
yeasts (highly refractile) are bound/phagocytized without the mAb. With
the
mAb, however, there is a substantial increase in the extent of
phagocytosis. Immune electron microscopy (below) shows that the epitope
that this mAb
binds can be seen in the cell wall and in clusters at the membrane-wall
interface (black gold particles show where the mAb has bound).
Click HERE to
see a complete image.
We're also doing some interesting work with a monoclonal antibody that
recognizes an epitope in bacterial peptidoglycan. (Merkel, G.J. and
B.A.
Scofield.2001. Characterization of a monoclonal antibody that binds to
an
epitope on soluble bacterial peptidoglycan fragments. Clin. Diag. Lab.
Immunol.
8: 647-651.) Click here to view the abstract. We are
currently engaged in animal studies to determine if anti-peptidoglycan
antibodies
can be used in an ELISA to diagnose bacteremia.
Most recently we've begun to study the interaction of Staphylococcus
epidermidis and S. aureus with human umbilical vein
endothelial cells, microvascular endothelial cells, and lung epithelial
cells in culture. Our most recent publication (Merkel & Scofield.
2001. Interaction of Staphylococcus epidermidis with
endothelial cells in vitro. Med. Microbiol. Immunol. 189:217-223) is
the first demonstration of heat-induced adherence and internalization
of S. epidermidis by human endothelial cells. Click HERE to see electron micrographs of S.
epidermidis
adhering to and invading endothelial cells. Most of our investigations
now
involve studies with Staphylococcus and microvascular
endothelial
cells since the microvasculature is probably the route that
staphylococci
use to disseminate from the blood into various tissues.
Click here for an old picture of me at work.
Merkel's Curriculum
Vitae
“Ode to Candida"(the yeast)
by Glenn Merkel
(written around 1983)
First Year Medical
Students:
Click HERE
for
information about Medical Microbiology and Immunology (Spring 2006).
Click to view the statewide Immunology
and Microbiology
cores (PDF
files).
Second Year Medical Students:
Click HERE
for
information about General Pathology (Fall 2005). All handouts are
available at the Angel Website:
https://daly.medicine.iu.edu/Med/frameIndex.htm
e-mail: merkel@ipfw.edu
Links:
(Last modified November 9, 2005)