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CURRENT CLINICAL
INTERESTS
General hematology/oncology, thrombosis, hypercoagulability
CURRENT RESEARCH
INTERESTS
Endothelial cell and leukocyte biology
RESEARCH DESCRIPTION
Inflammation and Vascular Biology.
. Leukocyte adherence to endothelium is a
critical event in host defense and repair, but may also contribute to
the pathogenesis of vascular and tissue injury in inflammatory and
immune disorders. Adhesive interactions between circulating leukocytes
and the vessel wall involve a cascade of events beginning with
low-affinity adhesion manifested by rolling under conditions of flow,
subsequent firm adhesion, and finally diapedesis between endothelial
cells (EC) and migration to the extravascular site of inflammation or
immune reaction. Using cell and molecular biology techniques and
gene-targeted mice, our current studies examine: 1) the regulation of
leukocyte integrin receptor avidity by high-density ligand and
cyclin-dependent kinases; and 2) the role of leukocyte VLA-4 integrin
in the progression of advanced atherosclerosis in murine models.
Recent studies also examine the mechanisms and
consequences of EC or leukocyte apoptosis during inflammatory
‘stress’. These studies involve in vitro investigation of the role
of apoptotic signaling pathways in EC and leukocyte activation.
Transgenic and gene-targeted mice are used to elucidate the
contribution of apoptosis in disease models of atherosclerosis,
ischemia-reperfusion injury, and sepsis.
SELECTED
PUBLICATIONS
Iwata A, Nishio K, Winn RK, Chi EY, Henderson WR Jr.,
Harlan JM. A broad-spectrum caspase inhibitor attenuates allergic airway inflammation in murine asthma model.
J. Immunol. 170: 3386-91, 2003.
Li X, Tupper J, Bannerman D, Rhodes C, Winn R, Harlan J.
Phosphoinositide 3 kinase mediates Toll-like receptor 4-induced activation of NF-kB in endothelial cells.
Infection and Immunity 71:4414-4420, 2003.
Iwata A, Morgan-Stevenson V, Minard A, Tasch M,
Tupper J, Lagasse E, Weissman, Harlan J, Winn
R. Over-expression of Bcl-2 provides protection in septic mice
by a ‘trans’ effect. J. Immunol. 171(6):3136-41, 2003.
Bannerman
DD, Eiting KT, Winn RK, Harlan JM. FLICE-like inhibitory protein
(FLIP) protects against apoptosis and suppresses NF-kappaB activation
induced by bacterial lipopolysaccharide. Am. J. Pathol.
165:1423-31, 2004.
Vanasse
GJ, Winn RK, Rodov S, Zieske AW, Li JT, Tupper JC, Tang J, Raines EW,
Peters MA, Yeung KY, Harlan JM.
Bcl-2 overexpression leads to increases in suppressor of
cytokine signaling-3 expression in B cells and de novo follicular
lymphoma. Mol. Cancer Res. 2:620-31, 2005.
Altemeier, W, Zhu X, Berrington W, Harlan J, Liles WC.
Fas (CD95) induces macrophage pro-Inflammatory chemokine
expression via a MyD88-dependent, Caspase-independent pathway. J.
Leuk. Biol. 82(3):721-8, 2007.
Taylor EL, Li JT, Tupper JC, Rossi AG, Winn RK,
Harlan JM. Peroxynitrite induces Bcl-2-sensitive, p53-independent
apoptosis in murine bone marrow cells. Biochem.
Pharmacol. 74(7):1039-49, 2007.
L
Liu, Schwartz B,
Tsubota Y, Raines E, Yonekawa K, Harlan
J (co-senior author), Schnapp L. Cyclin-dependent
kinase inhibitors block leukocyte adhesion and migration. J.
Immunol. 180(3):1808-17, 2008.
Helmers
AJ, Lovegrove FE, Harlan JM, Kain KC, Liles WC.
Failure of two distinct anti-apoptotic approaches to reduce
mortality in experimental cerebral malaria. Am .J. Trop. Med. Hyg.
79(6):823-5, 2008.
Becker
PS, Kopecky KJ, Wilks AN, Chien S, Harlan JM, Willman CL,
Petersdorf SH, Stirewalt DL, Papayannopoulou T, Appelbaum FR. Very
late antigen-4 function of myeloblasts correlates with improved
overall survival for patients with acute myeloid leukemia. Blood
113(4):866-74, 2009.
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