Cell Biology and Biochemistry
Gail A. Cornwall, Ph.D.
Ph.D. Reproductive Biology
Johns Hopkins Bloomberg School of Public Health
Department of Cell Biology and Biochemistry
Texas Tech University Health Sciences Center
3601 4th Street, Mail Stop 6540
Lubbock, TX 79430
Phone: (806) 743-2687
Fax: (806) 743-2990
Reproductive biology; sperm maturation and epididymal function. Amyloidogenesis; pathological
and functional amyloid in the male reproductive tract.
Functional role of the cystatin CRES in sperm maturation and fertilization.
The cystatin-related epididymal spermatogenic (CRES) protein defines a new subgroup
within the family 2 of the cystatin superfamily of cysteine protease inhibitors. CRES
and the seven other subgroup members exhibit reproductive-specific expression and
lack consensus sites for cysteine protease inhibition suggesting functions distinct
from that of typical family 2 cystatins. CRES is synthesized and secreted by the proximal
caput epididymal epithelium and is present within the lumen surrounding the maturing
spermatozoa suggesting roles in sperm maturation. CRES also localizes to the sperm
acrosome suggesting a functional role during fertilization. In this project we are
using a CRES gene knockout mouse model to determine CRES function within the epididymis
and spermatozoa to ultimately gain a better understanding of the mechanisms of sperm
maturation and fertilization.
Protein amyloidogenesis in the epididymis: mechanisms and biological signicance.
Proteins that misfold and form self-aggregates with a specific cross beta sheet fibrillar
structure are known as amyloids. Although generally associated with neurodegenerative
diseases such as Alzheimer’s and Huntington’s disease, amyloid structures have also
recently been found to carry out biological roles in some mammalian tissues and thus
are called functional amyloid. We have determined that CRES forms amyloid structures
in vitro similar to that present in pathological conditions raising the possibility
that CRES also forms amyloid in vivo within the epididymis. In this project we are
studying CRES amyloid within the epididymal lumen to determine whether it may represent
a functional amyloid. Alternatively, CRES amyloid may form a cytotoxic structure but
mechanisms are in place to protect against cytotoxicity and prevent damage to spermatozoa
- Egge, N., Muthusubramanian A, and Cornwall, G.A. (2015). Amyloid properties of the mouse egg zona pellucida. PLoS One. 2015 Jun 4;10(6):e0129907.
doi: 10.1371/journal.pone.0129907. eCollection 2015. PubMed
- Cornwall, G.A. (2014). Role of posttranslational protein modifications in epididymal sperm maturation
and extracellular quality control. Adv Exp Med Biol. 759:159-80. doi: 10.1007/978-1-4939-0817-2_8.
- Guyonnet B., Egge N., and Cornwall, G.A. (2014). Functional amyloids in the mouse sperm acrosome. Mol Cell Biol. 34:2624-34.
- Whelly, S., Serobian G., Borchardt C., Powell, J., Johnson, S., Hakansson, K., Lindstrom,
V., Abrahamson, M., Grubb, A., and Cornwall, G.A. (2014). Fertility defects in mice expressing the L68Q variant of human cystatin
C:a role for amyloid in male infertility. J Biol Chem 14;289:7718-29. PubMed
- Ferrer, M., Cornwall, G.A., Oko, R. (2013). A population of CRES resides in the outer dense fibers of spermatozoa.
Biol Reprod 88:1-9. PubMed
- Guyonnet, B., Zabet-Moghaddam, M., SanFrancisco, S., and Cornwall, G.A. (2012). Isolation and proteomic characterization of the mouse sperm acrosomal matrix.
Mol Cell Proteomics 11:758-774. PubMed
- Whelly, S., Johnson, S.S., Powell, J., Borchardt C., Hastert, M-C, and Cornwall, G.A. (2012). Nonpathological extracellular amyloid is present during normal epididymal
sperm maturation. Plos One, 10.1371/journal.pone.0036394. PubMed
- Tardif S., Guyonnet, B., Cormier, N., and Cornwall, G.A. (2012). Alteration in the processing of the ACRBP/sp32 protein and sperm head/acrosome
malformations in proprotein convertase 4 (PCSK4) null mice. Mol Human Reprod. 18:298-307.
Cover photo PubMed
- Cornwall, G.A., von Horsten, H.H., and Whelly, S. (2011). Cystatin-related epididymal spermatogenic
aggregates in the epididymis. J. Androl.32:679-85. PubMed
- Chau, K. and Cornwall, G.A. (2011). Impaired fertility in vitro in mice lacking the cystatin CRES (cystatin-related
epididymal spermatogenic): rescue by exposure of spermatozoa to dibutyryl cAMP/IBMX
Biol Reprod. 84:140-52. PubMed
- Parent, A.D., Cornwall, G.A., Liu, L.Y., Smith, C.E., and Hermo, L. (2011). Alterations in the testis and epididymis
associated with loss of function of the cystatin related epididymal spermatogenic
(CRES) protein. J Androl 32; 444-63. PubMed
- Cornwall, G.A. (2009). New insights into epididymal biology and function. Human Reproduction Update
- von Horsten, H.H., Johnson. S.S., SanFrancisco S.K., Hastert, M.C., Whelly, S., and
Cornwall, G.A. (2007). Oligomerization and transglutaminase crosslinking of the cystatin CRES in
the mouse epididymal lumen: Potential mechanism of extracellular quality control.
J. Biol. Chem. 282:32912-32923. PubMed
- Cornwall, G.A., von Horsten HH, Swartz D, Johnson S, Chau K, Whelly S. Extracellular quality control
in the epididymis. Asian J Androl (2007) 9:500-507. PubMed
- Sutton-Walsh, H.G., Whelly S, and Cornwall, G.A. (2006). Differential effects of GnRH and androgens on Cres (cystatin-related epididymal
spermatogenic) mRNA and protein expression in male mouse anterior pituitary gonadotroph
cells. J. Andrology 27:802-815. PubMed
- Hsia, N., Brousal, J., Hann, S.R., and Cornwall, G.A., (2005). Recapitulation of germ cell and pituitary-specific expression with 1.6 kb
of the cystatin-related epididymal spermatogenic (Cres) gene promoter in transgenic
mice. J. Andrology 26:249-257. PubMed
- Kirby, J.L., Yang, L., Labusm J.C., Lye, R.J., Hsia, N. Day, R., Cornwall, G.A., and Hinton, B.T. (2004). Characterization of epididymal epithelial cell-specific
gene promoters by in vivo electroporation. Biol. Reprod. 71: 613-619.PubMed
- Hsia , N. and Cornwall, G.A. (2004) Microarray analysis of region-specific gene expression in the mouse epididymis.
Biol. Reprod.70: 448-457.PubMed
- Cornwall, G.A., Cameron, A., Lindberg, I., Hardy, D., Cormier, N., and Hsia, N. (2003). CRES protein
inhibits the serine protease prohormone convertase PC2. Endocrinology 144:901-908.
- Cornwall, G.A. and Hsia, N. (2003). A new subgroup of the family 2 cystatins. Cutting Edge Reviews;
Molecular and Cellular Endocrinology. 200:1-8. PubMed
- Cooper TG, Wagenfeld A, Cornwall, G.A., Hsia N, Chu ST, Orgebin-Crist MC, Drevet J, Vernet P, Avram C, Nieschlag E, Yeung
CH. (2003). Gene and protein expression in the epididymis of infertile c-ros receptor
tyrosine kinase-deficient mice. Biol. Reprod. 69:1750-62. PubMed
- Hsia, N and Cornwall, G.A. (2003). Cres2 and Cres3: New members of the CRES subgroup of family 2 cystatins.
Endocrinology 144:909-915. PubMed