Daniel M. Hardy, Ph.D. | Texas Tech University Health Sciences Center

Daniel M. Hardy, Ph.D.

Professor

Daniel M. Hardy, Ph.D.
 

Ph.D. Medical Sciences/Biochemistry
University of New Mexico School of Medicine
Curriculum Vitae
Department of Cell Biology and Biochemistry
Texas Tech University Health Sciences Center
3601 4th Street, Lubbock, TX 79430-6540
Office Phone: (806) 743-2053
daniel.hardy@ttuhsc.edu

Research Interests

Reproductive biology: species diversity in animal fertilization
Evolutionary biology: protein molecular evolution, genomics, speciation
Zoonotic disease: prion diseases and viruses; inter-species transmission
Musculoskeletal biology: connective tissue growth, maintenance, and repair

Current Projects

Protein molecular evolution in animal fertilization and species divergence
In this project we study the rapid evolution of reproductive proteins with an emphasis on molecules that function in fertilization. We combine biochemical, cell and molecular, genomic and phylogenetic approaches to characterize proteins that promote reproductive isolation, including zonadhesin, the product of the speciation gene Zan that mediates taxon-specific recognition of the egg. The ongoing goal of this research is to identify speciation genes that act prezygotically, define the functions of their products in the gametes, and determine how species-differences in their activities drive species divergence. 

Protein molecular evolution in transmission of zoonotic disease
In this relatively new research direction we study molecular evolutionary processes underlying the transmissibility of diseases within and between species. The project applies our expertise in protein biochemistry, molecular biology, and phylogenetic analysis toward developing biomarker-based tests for infectious diseases, including Chronic Wasting Disease in deer transmitted by prions, and toward identifying potential zoonotic diseases in wild and domestic animals. The goal of this research is to establish an integrated, One Health-affiliated capability to identify potential zoonotic diseases, assess threat of cross-species transmission, conduct surveillance to monitor spread of disease, and conceive a pro-active plan for minimizing harm from future outbreaks.

Connective tissue remodeling and repair
In this project we characterize the production and degradation of structural proteins in connective tissues, with an emphasis on sex differences in maintenance and repair of the human anterior cruciate ligament (ACL) and on the age-associated causes and consequences of intervertebral disc degeneration. The research uses a comparative transcriptomics approach to identify 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 and disc function. The practical goal of this research is to prevent injury by understanding why female athletes are more prone to ACL injuries than their male counterparts, and why intervertebral discs are prone to herniation and rupture as people age. 

Selected Publications

Full publications list: Google Scholar

        • Cormier N, Worsham AE, Rich KA, Hardy DM (2024) SMA20/PMIS2 is a rapidly evolving sperm membrane alloantigen with possible species–divergent function in fertilization. Int J Mol Sci 25, 3652. PubMed
        • Roberts EK, Wright EA, Worsham AE, Hardy DM, Bradley RD (2023). Gamete recognition gene divergence yields a robust Eutherian phylogeny across taxonomic levels. Diversity 15, 1145. Selected as Editor’s Choice paper with graphical abstract. Publication
        • Ashton MN, Worsham AE, Strawn MD, Fisher GD, Perry CJ, Ferguson MP, Zumwalt M, Brindley G, Hashemi J, Mansouri H, Slauterbeck JR, Hardy DM (2023) Degraded RNA from human anterior cruciate ligaments yields valid gene expression profiles. Int J Mol Sci 24, 1895. Selected as Top View Paper of IJMS in 2023. PubMed
        • Bradley RD, Roberts EK, Worsham AE, Ashton MN, Wright EA, Saleh N, Hardy DM (2022). A non–invasive, biomarker assay for detecting chronic wasting disease pathology in white–tailed deer. BioRxiv (preprint). Preprint
        • Roberts EK, Tardif S, Wright EA, Platt II RN, Bradley RD, Hardy DM (2022). Rapid divergence of a gamete recognition gene promoted macroevolution of Eutheria. Genome Biol 23, 155. PubMed
        • Harakal J, Qiao H, Wheeler K, Rival C, Paul AGA, Hardy DM, Cheng CY, Goldberg E, Tung KSK (2022). Exposed and sequestered antigens in testes and their protection by regulatory T cell–dependent systemic tolerance. Frontiers Immunol 13, 809247. PubMed
        • 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
        • 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
        • 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, 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
        • 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
        • 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