Mark Geraci, M.D.
Associate Professor
Microarray expression analysis to study disease pathogenesis. Eicosanoid
biology in pulmonary vascular disease and lung cancer
Research Interests
My laboratory has two principal research foci. The first is the role of eicosanoids in pulmonary hypertension and lung cancer: We previously cloned full-length rat prostacyclin synthase (PGIS) cDNA, demonstrated decreased PGIS in primary pulmonary hypertension, and developed transgenic mice with pulmonary specific overexpression of PGIS, which are completely protected from developing pulmonary hypertension. We then developed a variety of transgenic, bi-transgenic, and knockout animals in the eicosanoids pathway including transgenic animals with lung-specific overexpression of cPLA2, COX-2, PGIS (Prostacyclin Synthase), PGIS with tetracycline-on inducible expression in both CC10 and SPC “activator” mice, and membrane PGES (Prostaglandin E2 Synthase). We are currently using all of these murine models to study the effects of various eicosanoids members, and their metabolites, in murine models of pulmonary vascular disease and lung tumorigenesis.
Our second area of interest is the use of gene expression analysis to
study disease pathogenesis. The revolution in genomics has made possible
the large-scale analysis of multiple genes by gene array technology and
the real time quantification of RNA. I direct the UCD Gene Expression
Core Facility, with particular focus on diseases of the heart, lung and
blood.
Publications
Geraci, M. W., Gao, B., Shepherd, D. C., Moore, M. D., Westcott,
J. Y., Fagan, K. A., Alger, L. A., Tuder, R. M., and Voelkel, N. F. Pulmonary
prostacyclin synthase overexpression in transgenic mice protects against
development of hypoxic pulmonary hypertension. J.Clin.Invest, 103: 1509-1515,
1999.
Tuder, R. M., Cool, C. D., Geraci, M. W., Wang, J., Abman, S. H., Wright,
L., Badesch, D., and Voelkel, N. F. Prostacyclin synthase expression is
decreased in lungs from patients with severe pulmonary hypertension. American
Journal of Respiratory & Critical Care Medicine, 159: 1925-1932, 1999.
Gupta, R. A., Tan, J., Krause, W. F., Geraci, M. W., Willson, T. M., Dey,
S. K., and DuBois, R. N. Prostacyclin-mediated activation of peroxisome
proliferator-activated receptor delta in colorectal cancer . Proc.Natl.Acad.Sci.U.S.A,
97: 13275-13280, 2000.
Golpon, H. A., Geraci, M. W., Moore, M. D., Miller, H. L., Miller, G.
J., Tuder, R. M., and Voelkel, N. F. HOX genes in human lung: altered
expression in primary pulmonary hypertension and emphysema. Am.J.Pathol.,
158: 955-966, 2001.
Geraci, M. W., Gao, B., Hoshikawa, Y., Yeager, M. E., Tuder, R. M., and
Voelkel, N. F. Genomic approaches to research in pulmonary hypertension.
Respir.Res., 2: 210-215, 2001.
Hoshikawa, Y., Voelkel, N. F., Gesell, T. L., Moore, M. D., Morris, K.
G., Alger, L. A., Narumiya, S., and Geraci, M. W. Prostacyclin receptor-dependent
modulation of pulmonary vascular remodeling. Am.J.Respir.Crit Care Med.,
164: 314-318, 2001.
Geraci, M. W., Moore, M., Gesell, T., Yeager, M. E., Alger, L., Golpon,
H., Gao, B., Loyd, J. E., Tuder, R. M., and Voelkel, N. F. Gene expression
patterns in the lungs of patients with primary pulmonary hypertension:
a gene microarray analysis. Circ.Res., 88: 555-562, 2001.
Tuder, R. M., Yeager, M. E., Geraci, M., Golpon, H. A., and Voelkel, N.
F. Severe pulmonary hypertension after the discovery of the familial primary
pulmonary hypertension gene. Eur.Respir.J., 17: 1065-1069, 2001.
Tuder, R. M., Chacon, M., Alger, L., Wang, J., Taraseviciene-Stewart,
L., Kasahara, Y., Cool, C. D., Bishop, A. E., Geraci, M., Semenza, G.
L., Yacoub, M., Polak, J. M., and Voelkel, N. F. Expression of angiogenesis-related
molecules in plexiform lesions in severe pulmonary hypertension: evidence
for a process of disordered angiogenesis. J.Pathol., 195: 367-374, 2001.
Parker, T. A., Afshar, S., Kinsella, J. P., Grover, T. R., Gebb, S., Geraci,
M., Shaul, P. W., Cryer, C. M., and Abman, S. H. Effects of chronic estrogen-receptor
blockade on ovine perinatal pulmonary circulation. Am.J.Physiol Heart
Circ.Physiol, 281: H1005-H1014, 2001.
Cosgrove, G. P., Schwarz, M. I., Geraci, M. W., Brown, K. K., and Worthen,
G. S. Overexpression of matrix metalloproteinase-7 in pulmonary fibrosis.
Chest, 121: 25S-26S, 2002.
Geraci, M. W., Hoshikawa, Y., Yeager, M., Golpon, H., Gesell, T., Tuder,
R. M., and Voelkel, N. F. Gene expression profiles in pulmonary hypertension.
Chest, 121: 104S-105S, 2002.
Keith, R. L., Miller, Y. E., Hoshikawa, Y., Moore, M. D., Gesell, T. L.,
Gao, B., Malkinson, A. M., Golpon, H. A., Nemenoff, R. A., and Geraci,
M. W. Manipulation of pulmonary prostacyclin synthase expression prevents
murine lung cancer. Cancer Res., 62: 734-740, 2002.
Spalding, A. C., Jotte, R. M., Scheinman, R. I., Geraci, M. W., Clarke,
P., Tyler, K. L., and Johnson, G. L. TRAIL and inhibitors of apoptosis
are opposing determinants for NF- kappaB-dependent, genotoxin-induced
apoptosis of cancer cells. Oncogene, 21: 260-271, 2002.
Voelkel, N. F., Cool, C., Taraceviene-Stewart, L., Geraci, M. W., Yeager,
M., Bull, T., Kasper, M, and Tuder, R. M. Janus face of vascular endothelial
growth factor: The obligatory survival factor for lung vascular endothelium
controls precapillary artery remodeling in severe pulmonary hypertension.
Crit Care Med., 30 Suppl: S251-S256, 2002.
Sugita, M., Geraci, M., Gao, B., Powell, R. L., Hirsch, F. R., Johnson,
G., Lapadat, R., Gabrielson, E., Bremnes, R., Bunn, P. A., and Franklin,
W. A. Combined use of oligonucleotide and tissue microarrays identifies
cancer/testis antigens as biomarkers in lung carcinoma. Cancer Res., 62:
3971-3979, 2002.
Wick, M., Hurteau, G., Dessev, C., Chan, D., Geraci, M. W., Winn, R. A.,
Heasley, L. E., and Nemenoff, R. A. Peroxisome Proliferator-Activated
Receptor-gamma Is a Target of Nonsteroidal Anti-Inflammatory Drugs Mediating
Cyclooxygenase- Independent Inhibition of Lung Cancer Cell Growth. Mol.Pharmacol.,
62: 1207-1214, 2002.
Hoshikawa, Y., Nana-Sinkam, P., Moore, M. D., Sotto-Santiago, S., Phang,
T., Keith, R. L., Morris, K. G., Kondo, T., Tuder, R. M., Voelkel, N.
F., and Geraci, M. W. Hypoxia induces different genes in the lungs of
rats when compared with mice. Physiol Genomics, 12:209-219, 2003.
Ameshima S, Golpon H, Cool CD, Chan D, Nemenoff RA, Geraci MW, Voelkel
NF. Peroxisome proliferator-activated receptor gamma (PPAR?) expression
is decreased in pulmonary hypertension and affects endothelial cell growth.
Circ. Res. 92(10):1162-9, 2003.
Bull, T.M., Cool, C.D., Serls, A.E., Pradeep, R.R., Parr, J., Yeager,
M., Neid, J.M., Geraci, M.W., Campbell, T.B., Voelkel, N.F., and Badesch,
D.B. Primary pulmonary hypertension, Castleman’s disease and HHV-8
European Respiratory Journal, 22: 403-407, 2003.
Bull, T.M., Golpon, H., Hebbel, R.P., Solovey, A., Cool, C.D., Tuder,
R.M., Geraci, M.W., and Voelkel, N.F. Circulating endothelial cells in
pulmonary hypertension. Thrombosis and Haemostasis, 90:698-703, 2003 .
Barash, Y., Dehan, E., Krupsky, M., Franklin, W., Geraci, M., Friedman,
N., and Kaminski, N. Comparative analysis of algorithms for signal quantitation
from oligonucleotide microarrays. In Press, Bioinformatics, 2004.
Cool, C.D., Rai, P.R., Yeager, M.E., Hernandez-Saavedra, D., Serls, A.E.,
Bull, T.M., Geraci, M.W., Brown, K.K., Routes, J.M., Tuder, R.M., Voelkel,
N.F. Human Herpes Virus 8 (HHV-8) Expression in Primary Pulmonary Hypertension.
New England Journal of Medicine, 349 (12): 1113-1122, 2003.
