# positions[].organizations[].parent[].label
School of Veterinary Medicine and Biomedical Sciences

# positions[].organizations[].parent[].label
School of Veterinary Medicine and Biomedical Sciences

# overview
My laboratory has been engaged in multiple areas of NIH-funded musculoskeletal research since 1996. We were the first to identify the non-steroidal gonadal inhibin hormones in regulating the hypothalamic-pituitary-gonadal-skeletal axis in mice, and the role of changes in inhibins that signal the onset of menopause (reproductive aging) to the onset of increasing bone turnover. We also demonstrated the anabolic effect of continual Inhibin exposure in normal mice and in bone repair.  Our cellular focus on Inhibins and the related factor, Activin A revealed that Activin A suppresses local bone resorption through suppression of osteoclast formation, motility and survival. Our ongoing work is in the area of specific inhibin/betaglycan receptor interactions that mediate the effects on bone cells. We are also greatly interested in improving the low bone mass that we were the first to identify in both humans with Down Syndrome (DS) and in mouse models of DS as a low bone turnover disease. Our current NIH-funded research is working to identify the mechanisms of reduced fracture healing and compromised bone regeneration in Down Syndrome. We have demonstrated the efficacy of both PTH and SclAb in DS, and are now actively testing nutriceuticals to increase bone mass in mouse models of Down Syndrome. The limitations of using mouse models to study bone disease led us to our most recent and exciting endeavors in collaboration with TAMU experts in reproduction and embryo transfer technologies to develop a large platform model of bone disease, using sheep. We have generated the first large animal model of hypophosphatasia (HPP) via high efficiency gene editing of a knock-in point mutation in the ALPL gene, whose musculoskeletal and dental phenotypes are consistent with human HPP. We are now using this model to determine the etiology of mineralization deficiencies, muscle weakness and premature tooth loss by analysis of longitudinal biopsies and analysis of muscle, bone and dental specimens using CT, microCT, mechanical testing, immunohistochemistry, histomorphometry and ex vivo bone marrow cultures.

# keywords[]
Diseases And Disorders Of/related To Bone

# keywords[]
Endosomal Sorting Complexes Required For Transport

# keywords[]
Receptor Activator Of Nuclear Factor-kappa B

# keywords[]
Receptor Activator Of Nuclear Factor-kappa B

# keywords[]
Reverse Transcriptase Polymerase Chain Reaction

# keywords[]
Diseases And Disorders Of/related To Bone

# keywords[]
Reverse Transcriptase Polymerase Chain Reaction

# keywords[]
Reverse Transcriptase Polymerase Chain Reaction

# keywords[]
Receptor Activator Of Nuclear Factor-kappa B

# educationAndTraining[].organization.label
University of Arkansas at Little Rock - (Little Rock, Arkansas, United States)

# educationAndTraining[].organization.label
Texas A&M University - (College Station, Texas, United States)

# educationAndTraining[].organization.label
Salk Institute for Biological Studies - (La Jolla, California, United States)

# educationAndTraining[].organization.label
Baylor College of Medicine - (Houston, Texas, United States)

# awardsAndHonors[].label
ASBMR John Haddad Young Investigator Award

# publications[].label
ANALYSIS OF ESTROGEN-INDUCED UTERINE MYOMETRIAL CELL GAP-JUNCTIONS

# publications[].label
Mouse digit bone regeneration: A new model to study cell-specific effects of aging on bone repair

# publications[].label
Breast cancer metastasis to bone: it is not all about PTHrP.

# publications[].label
PTHrP(12-48) Modulates the Bone Marrow Microenvironment and Suppresses Human Osteoclast Differentiation and Lifespan.

# publications[].label
FGF and Klotho Phosphate Regulatory Pathways Linking Placenta and Bone

# publications[].label
Gap junction modulation in rat uterus. III. Structure-activity relationships of estrogen receptor-binding ligands on myometrial and serosal cells.

# publications[].label
Bisphosphonates in veterinary medicine: The new horizon for use.

# publications[].label
Muscle Weakness and Fiber Type Redistribution May Explain the Diminished Mobility and Compromised Kinematics in Hypophosphatasia

# publications[].label
Activin inhibits binding of transcription factor Pit-1 to the growth hormone promoter.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Effects of exogenous progesterone on the expression of mineral regulatory molecules by ovine endometrium and placentomes.

# publications[].label
Digit specific denervation does not inhibit mouse digit tip regeneration.

# publications[].label
Inhibin and the regulation of bone mass.

# publications[].label
Hormonal regulation, tissue distribution, and content of aromatase cytochrome P450 messenger ribonucleic acid and enzyme in rat ovarian follicles and corpora lutea: relationship to estradiol biosynthesis.

# publications[].label
Circulating interleukin-8 levels explain breast cancer osteolysis in mice and humans.

# publications[].label
Hyaline cartilage differentiation of fibroblasts in regeneration and regenerative medicine.

# publications[].label
Sex and Diet Specific Differences In Bone Mass of 4 Mouse Strains: Can Mice Tell Us What to Eat for Bone Health?

# publications[].label
Inhibin A enhances bone formation during distraction osteogenesis.

# publications[].label
Differential muscle fiber typing and energetics defines a muscle weakness phenotype in HPP sheep

# publications[].label
The somatotrope as a metabolic sensor: deletion of leptin receptors causes obesity.

# publications[].label
Degenerative Tissue Responses to Space-like Radiation Doses in a Rodent Model of Simulated Microgravity.

# publications[].label
Hormonal regulation and tissue-specific localization of alpha 2-macroglobulin in rat ovarian follicles and corpora lutea.

# publications[].label
Inhibin A is an endocrine stimulator of bone mass and strength.

# publications[].label
Pressure hyperalgesia in hind limb suspended rats.

# publications[].label
Differential skeletal responses of hindlimb unloaded rats on a vitamin D-deficient diet to 1,25-dihydroxyvitamin D3 and its analog, seocalcitol (EB1089).

# publications[].label
Rapid loss of bone mass and strength in mice after abdominal irradiation.

# publications[].label
Epimorphic regeneration of the mouse digit tip is finite.

# publications[].label
Interaction of Brucella abortus with Osteoclasts: a Step toward Understanding Osteoarticular Brucellosis and Vaccine Safety.

# publications[].label
Sclerostin Antibody Treatment Stimulates Bone Formation to Normalize Bone Mass in Male Down Syndrome Mice.

# publications[].label
Expression characterization and functional implication of the collagen-modifying Leprecan proteins in mouse gonadal tissue and mature sperm.

# publications[].label
Gestational exposure to nicotine administered by e-cig juice accelerates osteogenesis and bone formation in dams, but suppresses bone growth and development in the pups

# publications[].label
Physiological role of mGSTA4-4, a glutathione S-transferase metabolizing 4-hydroxynonenal: generation and analysis of mGsta4 null mouse.

# publications[].label
Genetic engineering a sheep model of Hypophosphatasia.

# publications[].label
Activin A inhibits RANKL-mediated osteoclast formation, movement and function in murine bone marrow macrophage cultures.

# publications[].label
Modeling Hypophosphatasia in Ovies aries (sheep) using CRISPR/Cas9: Development of large animal models that phenocopy rare human bone diseases

# publications[].label
Aging alters the skeletal response to disuse in the rat.

# publications[].label
Insulin facilitation of muscle protein synthesis following resistance exercise in hindlimb-suspended rats is independent of a rapamycin-sensitive pathway.

# publications[].label
Male mice with elevated C-type natriuretic peptide-dependent guanylyl cyclase-B activity have increased osteoblasts, bone mass and bone strength.

# publications[].label
Hormonal regulation of estradiol biosynthesis, aromatase activity, and aromatase mRNA in rat ovarian follicles and corpora lutea.

# publications[].label
Novel mineral regulatory pathways in ovine pregnancy: I. phosphate, klotho signaling, and sodium-dependent phosphate transporters.

# publications[].label
Development and characterization of a hypophosphatasia (HPP) tooth and muscle phenotype in sheep to model disease in an index HPP patient

# publications[].label
Differential muscle fiber typing and energetics defines a muscle weakness phenotype in HPP sheep

# publications[].label
Bone turnover across the menopause transition : The role of gonadal inhibins.

# publications[].label
Impact of sarA and Phenol-Soluble Modulins on the Pathogenesis of Osteomyelitis in Diverse Clinical Isolates of Staphylococcus aureus.

# publications[].label
Dental defects in the primary dentition associated with hypophosphatasia from biallelic ALPL mutations.

# publications[].label
Genetic engineering a large animal model of human hypophosphatasia in sheep.

# publications[].label
Matrix metalloproteinases in multiple myeloma.

# publications[].label
Low bone mass and impaired fracture healing in mouse models of Trisomy21 (Down syndrome).

# publications[].label
Imaging bone blood perfusion: not just going with the flow.

# publications[].label
Low bone turnover and low BMD in Down syndrome: effect of intermittent PTH treatment.

# publications[].label
The Skeletal Phenotype of Mice Deficient in Liver Fatty Acid Binding Protein-1 (L-FABP-1) is Increased Bone Marrow Fat and Bone Mass.

# publications[].label
Gap junction modulation in rat uterus. I. Effects of estrogens on myometrial and serosal cells.

# publications[].label
PANCREATIC HISTOLOGY AND ASSOCIATED BIOCHEMICAL CHANGES IN RATS ON HINDLIMB SUSPENSION

# publications[].label
Novel mineral regulatory pathways in ovine pregnancy: II. Calcium-binding proteins, calcium transporters, and vitamin D signaling.

# publications[].label
Regulation of alpha 2-macroglobulin by luteinizing hormone and prolactin during cell differentiation in the rat ovary.

# publications[].label
Dentoalveolar Defects of Hypophosphatasia are Recapitulated in a Sheep Knock-In Model.

# publications[].label
Predictive estimation of ovine hip joint centers: A regression approach.

# publications[].label
Towards mechanisms of bone regeneration and repair. Lessons learned from African spiny mice (Acomys)

# publications[].publisher
American Association for Cancer Research (AACR)

# publications[].label
Development of a longitudinal injury prevention curriculum for undergraduate medical students.

# publications[].label
Back to the Future: Evaluation of the Role of Glutamate in Bone Cells.

# publications[].label
A rat resistance exercise regimen attenuates losses of musculoskeletal mass during hindlimb suspension.

# publications[].label
Effect of flywheel-based resistance exercise on processes contributing to muscle atrophy during unloading in adult rats.

# publications[].label
Hormonal causes of menopausal bone resorption.

# publications[].label
Expression of interleukin 8 and not parathyroid hormone-related protein by human breast cancer cells correlates with bone metastasis in vivo.

# publications[].label
Regulation of bone mass by mechanical loading: microarchitecture and genetics.

# publications[].label
Impaired Fracture Healing in Dp16 Down Syndrome Mice

# publications[].label
Consistent Dental Defects Associated with ALPL Mutations in Humans and Sheep with Hypophosphatasia

# publications[].label
Exogenous Progesterone in Early Pregnancy has Programming Effects on Phosphate, Calcium, and Vitamin D Signaling in the Ovine Endometrium and Placenta in Late Pregnancy

# publications[].label
Protooncogene junB as a target for activin actions.

# publications[].label
Tumor-derived interleukin-8 stimulates osteolysis independent of the receptor activator of nuclear factor-kappaB ligand pathway.

# publications[].publisher
American Association for Cancer Research (AACR)

# publications[].label
Sc65 is a novel endoplasmic reticulum protein that regulates bone mass homeostasis.

# publications[].label
Osteopenia in a Mouse Model of Spinal Cord Injury: Effects of Age, Sex and Motor Function.

# publications[].label
Identification of PTHrP(12-48) as a plasma biomarker associated with breast cancer bone metastasis.

# publications[].publisher
American Association for Cancer Research (AACR)

# publications[].label
Bone is a target for the antidiabetic compound rosiglitazone.

# publications[].label
Bone healing in response to S. aureus infection is associated with rapid initiation of neutrophil and osteoclast invasion, and bone resorption prior to aberrant bone healing

# publications[].label
Microcomputed tomography staging of bone histolysis in the regenerating mouse digit.

# publications[].label
Activin increases phosphorylation and decreases stability of the transcription factor Pit-1 in MtTW15 somatotrope cells.

# publications[].label
Effects of progesterone and interferon tau on ovine endometrial phosphate, calcium, and vitamin D signaling.

# publications[].label
The effect of host tissue irradiation on large-segment allograft incorporation.

# publications[].label
Male specific low bone mass phenotype in Down Syndrome humans and mouse models

# publications[].label
Mouse digit bone regeneration: A new model to study cell-specific effects of aging on bone repair

# publications[].label
Insulin-facilitated increase of muscle protein synthesis after resistance exercise involves a MAP kinase pathway.

# publications[].label
Impaired Mitochondrial Respiration and Altered Fiber Type in Hlypophosphatasia Sheep Skeletal Muscle

# publications[].label
Inhibitor of DASH proteases affects expression of adhesion molecules in osteoclasts and reduces myeloma growth and bone disease.

# publications[].label
Sex Differences in the Skeletal Phenotype of the African Spiny Mouse (Acomys cahirinus)

# publications[].label
Inhibin suppresses and activin stimulates osteoblastogenesis and osteoclastogenesis in murine bone marrow cultures.

# publications[].label
Low bone turnover and low bone density in a cohort of adults with Down syndrome.

# publications[].label
Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1.

# publications[].label
Bone turnover across the menopause transition: correlations with inhibins and follicle-stimulating hormone.

# publications[].label
Engineering bone phenotypes in domestic animals: Unique resources for enhancing musculoskeletal research.

# publications[].label
Activins and the receptor serine kinase superfamily.

# publications[].label
Nuclear translocation of EndoG at the initiation of disuse muscle atrophy and apoptosis is specific to myonuclei.

# publications[].label
Clodronate improves lameness in horses without changing bone turnover markers.

# publications[].label
Delayed Bone Regeneration in Down Syndrome Mice following P3 Digit Amputation

# publications[].label
Regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones, Activin and Inhibin.

# publications[].label
Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease.

# publications[].label
Activation of guanylyl cyclase-B increases long bone mass, density and strength

# publications[].label
Towards mechanisms of bone regeneration and repair. Lessons learned from African spiny mice (Acomys)

# publications[].label
Mouse Digit Tip Regeneration Is Mechanical Load Dependent.

# publications[].label
Induction of adenosine 3',5'-monophosphate-dependent protein kinase subunits during adipogenesis in vitro.

# publications[].label
Modeling Hypophosphatasia in Ovies aries (sheep) using CRISPR/Cas9: Development of large animal models that phenocopy rare human bone diseases

# publications[].label
The best of both worlds - managing the cancer, saving the bone.

# publications[].label
Guanylyl Cyclase-B Dependent Bone Formation in Mice is Associated with Youth, Increased Osteoblasts, and Decreased Osteoclasts.

# publications[].label
Prostaglandin endoperoxide synthase in rat ovarian follicles: content, cellular distribution, and evidence for hormonal induction preceding ovulation.

# researcherOn[].label
Veterinary Medical Student Research Training

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].label
Understanding the skeleton in Down Syndrome

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].label
Modeling Odontohypophosphatasia in the Sheep

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of Dental and Craniofacial Research

# streetAddress
Texas A&M University; Veterinary Integrative Biosciences; 4458 TAMU

# schools[]
School of Veterinary Medicine and Biomedical Sciences