Cell Biology and Biochemistry
Daniel M. Hardy, Ph.D.
Ph.D. Medical Sciences/Biochemistry
University of New Mexico School of Medicine, 1986
Department of Cell Biology and Biochemistry
Texas Tech University Health Sciences Center
3601 4th Street, Mail Stop 6540
Lubbock, TX 79430
Phone: (806) 743-2053
Fax: (806) 743-2990
Reproductive biology; biochemistry of animal fertilization. Musculoskeletal biology;
biochemistry of connective tissue growth, maintenance, and repair.
Characterization of sperm protein function in egg recognition.
In this project we are studying the function of egg adhesion molecules in the sperm
acrosome with an emphasis on understanding how a rapidly evolving protein, zonadhesin,
mediates species-specific recognition of the egg’s zona pellucida. The ultimate goal
of this research is to define the biochemical basis of sperm-egg recognition, and
thereby understand how this interaction contributes to reproductive isolation and
the evolution of new species.
Defining the sperm-specific proteome.
In this project we are identifying novel sperm-specific proteins immunochemically
with anti-sperm allo- and auto-antibodies, and characterizing the functions of these
proteins in fertilization. The ultimate goal of this research is to produce a complete
inventory of sperm-specific proteins and determine how their activities collectively
account for the sperm cell’s unique ability to fertilize the egg. A practical outcome
of this work will be identification of targets for immunocontraceptives that block
Sex differences in ligament remodeling and repair.
In this project we are characterizing sex differences in the production and degradation
of structural proteins of the human anterior cruciate ligament (ACL). The research
uses a microarray-based, comparative transcriptomics approach to identify sex differences
in the expression of genes encoding collagen and other extracellular matrix proteins,
as well as matrix metalloproteases. The molecular results are correlated with ultrastructural
and biomechanical data to build a comprehensive molecular to physical understanding
of ligament function. One practical goal of this research is to understand why female
athletes are more prone to ACL injuries than their male counterparts, and then to
use the information to prevent injury.
Pathogenesis of intervertebral disc degeneration
In this project we are studying the causes and consequences of age-associated degeneration
of human intervertebral discs, the cushions between vertebrae of the spine. This research
also uses comparative transcriptomics to identify genes encoding extracellular matrix
components whose expression levels correlate with disc biomechanical properties and
extent of degeneration. A goal of this research is to understand why intervertebral
discs are prone to herniation and rupture as people age.
- Hashemi J, Mansouri H, Chandrashekar N, Slauterbeck JR, Hardy DM, Beynnon BD (2011) Age, sex, body anthropometry, and ACL size predict the structural
properties of the human anterior cruciate ligament. J Orthop Res 29, 993-1001. PubMed
- Wheeler K, Tardif S, Rival C, Luu B, Bui E, Del Rio R, Sparwasser T, Teuscher C, Hardy DM, Tung KSK (2011) Regulatory T cells control tolerogenic versus autoimmune response
to sperm in vasectomized mice. Proc Natl Acad Sci USA 108, 7511-7516. PubMed
- Hashemi J, Breighner R, Chandrashekar N, Hardy DM, Chaudhari AM, Shultz SJ, Slauterbeck JR, Beynnon BD (2011) Hip-extension, knee-flexion
paradox: A new mechanism for non-contact ACL injury. J Biomechanics 44, 577-585. PubMed
- Tardif S, Akrofi A, Dass B, Hardy DM, MacDonald CC (2010) Infertility with impaired zona pellucida adhesion of spermatozoa
from mice lacking tCstf-64. Biol Reprod 83, 464-472. PubMed
- Tardif S, Wilson MD, Wagner R, Hunt P, Gertsenstein M, Nagy A, Lobe C, Koop BF, Hardy DM (2010) Zonadhesin is essential for species specificity of sperm adhesion to the egg
zona pellucida. J Biol Chem 285, 24863-24870. PubMed
- Peteiro-Gonzalez D, Lee J, Rodriguez-Fontan J, Castro-Piedras I, Cameselle-Teijeiro
J, Beiras A, Bravo SB, Alvarez CV, Hardy DM, Targovnik HM, Arvan P, Lado-Abeal J (2010) New insights into thyroglobulin pathophysiology
revealed by the study of a family with congenital goiter. J Clin Endocrinol Metab
95, 3522-3526. PubMed
- Tardif S, Brady HA, Braezeale KR, Bi M, Thompson LD, Bruemmer JE, Bailey LB, Hardy DM (2010) Zonadhesin D3-polypeptides vary among species but are similar in Equus species
capable of interbreeding. Biol Reprod 82, 413-421. PubMed
- Hashemi J, Chandrashekar N, Mansouri H, Slauterbeck JR, Hardy DM (2008) The human anterior cruciate ligament: sex differences in ultrastructure and
correlation with biomechanical properties. J Orthop Res 26, 945-950.
- Bi M, Winfrey VP, Olson GE, Hardy DM (2003) Processing, localization, and binding activity of zonadhesin suggest a function
in sperm adhesion to the zona pellucida during exocytosis of the acrosome. Biochem
J 375, 477-488.
- Slauterbeck JR, Fuzie S, Smith MP, Clark RJ, Xu KT, Hardy DM (2002) The menstrual cycle, sex hormones, and anterior cruciate ligament injury.
J Athletic Training 37, 275-280. PubMed
- Hickox JR, Bi M, Hardy DM (2001). Heterogeneous processing and zona pellucida binding activity of pig zonadhesin.
J Biol Chem 276, 41502-41509. PubMed
- Wilson MD, Riemer C, Martindale DW, Schnupf P, Boright AP, Cheung TL, Hardy DM, Schwartz S, Scherer SW, Tsui L-C, Miller W, Koop BF (2001). Comparative analysis
of the gene dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region
on mouse chromosome 5. Nucleic Acids Res 29, 1352-1365. PubMed
- Foos MJ, Hickox JR, Mansour PG, Slauterbeck JR, Hardy DM (2001). Expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase
genes in human anterior cruciate ligament. J Orthop Res 19, 642-649. PubMed
- Haden NP, Hickox JR, Whisnant CS, Hardy DM (2000) Systematic characterization of sperm-specific membrane proteins in swine.
Biol Reprod 63, 1839-1847. PubMed
- Hardy DM, Garbers DL (1995) A sperm membrane protein that binds in a species specific manner
to the egg extracellular matrix is homologous to von Willebrand factor. J Biol Chem
270, 26025-26028. PubMed
- Hardy DM, Garbers DL (1994) Species-specific binding of sperm proteins to the extracellular
matrix (zona pellucida) of the egg. J Biol Chem 269, 19000-19004. PubMed
- Hardy DM, Oda MN, Friend DS, Huang TTF Jr (1991) A mechanism for differential release of acrosomal
enzymes during the acrosome reaction. Biochem J 275, 759-766. PubMed