Daniel M. Hardy, Ph.D.
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 sperm-egg interaction.
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.
Full publications list: Google Scholar
- Cormier N, McGlone J, Leszyk J, Hardy DM (2018) Immunocontraceptive repertoire defined by systematic identification of major sperm membrane and lipid raft alloantigens in a single species.PLoS One13, e0190891. PubMed
- Tung KSK, Harakal J, Qiao H, Rival C, Li J, Paul AG, Wheeler K, Pramoonjago P, Grafer CM, Sun W, Sampson RD, Wong EW, Reddi PP, Deshmukh US, Hardy DM, Tang H, Cheng CY, Goldberg E (2017) Egress of sperm autoantigen from seminiferous tubules maintains systemic tolerance. J Clin Invest 127, 1046-1060. PubMed
- Tourville TW, Shultz SJ, Vacek PM, Knudsen EJ, Bernstein IM, Tourville KJ, Hardy DM, Slauterbeck JR, Johnson RJ, Beynnon BD (2016) Evaluation of an algorithm to predict menstrual cycle phase at the time of injury. J Athletic Training 51, 47-56. PubMed
- Tanphaichitr N, Kongmanas K, Kruevaisayawan H, Saewu A, Sugeng C, Fernandes J, Souda P, Angel JB, Faull KF, Aitken RJ, Whitlegge J, Hardy D, Berger T, Baker M (2015) Remodeling of the plasma membrane in preparation for sperm-egg recognition: roles of acrosomal proteins. Asian J Androl 17, 1-9. PubMed
- Kongmanas K, Kruevaisayawan H, Saewu A, Sugeng C, Fernandes J, Souda P, Angel JB, Kitajima K, Faull KF, Aitken RJ, Whitelegge J, Hardy D, Berger T, Baker MA, Tanphaichitr N (2015) Proteomic characterization of sperm anterior head plasma membrane vesicles reveals the roles of acrosomal proteins in ZP3 binding. J Cell Physiol 230, 449-463. PubMed
- Rival C, Wheeler K, Jeffrey S, Qiao H, Lu, Tewalt E, Engelhard V, Tardif S, Hardy D, del Rio R, Teuscher C, Tung K (2013) Regulatory T cells in vasectomy. J Reprod Immunol 100, 66-75. PubMed
- 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
- 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. PubMed
- 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. PubMed
- 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