Ralph Marcucio, PhD

Professor
Department of Orthopaedic Surgery

First, using cutting-edge genomic technology, Dr. Marcucio is examining how the entire genome responds to orthopaedic trauma. This genome-mining approach is aimed at determining the global genome response during fracture repair and allows the possibility to generate improved, highly innovative therapies for people undergoing fracture repair. Second, Ralph is examining the role that the brain plays during normal development of the facial skeleton. Many facial birth defects have an underlying brain malformation, and the goal of the research is to generate novel therapeutic approaches that will allow correcting facial malformations prior to birth.

Research Summary: 
Craniofacial development, evolutionary biology, trauma, bone repair, angiogenesis
Publications: 

Non-linear gene expression-phenotype relationships contribute to variation and clefting in the A/WySn mouse.

Developmental dynamics : an official publication of the American Association of Anatomists

Green RM, Leach CL, Diewert VM, Aponte JD, Schmidt EJ, Cheverud JM, Roseman CC, Young NM, Marcucio RS, Hallgrimsson B

Differential fracture response to traumatic brain injury suggests dominance of neuroinflammatory response in polytrauma.

Scientific reports

Morioka K, Marmor Y, Sacramento JA, Lin A, Shao T, Miclau KR, Clark DR, Beattie MS, Marcucio RS, Miclau T, Ferguson AR, Bresnahan JC, Bahney CS

Integration and the Developmental Genetics of Allometry.

Integrative and comparative biology

Hallgrímsson B, Katz D, Aponte JD, Larson JE, Devine J, Gonzalez P, Young NM, Roseman CC, Marcucio RS

Fracture repair in the elderly: Clinical and experimental considerations.

Injury

Meinberg EG, Clark D, Miclau KR, Marcucio R, Miclau T

Chronic psychosocial stress compromises the immune response and endochondral ossification during bone fracture healing via ß-AR signaling.

Proceedings of the National Academy of Sciences of the United States of America

Haffner-Luntzer M, Foertsch S, Fischer V, Prystaz K, Tschaffon M, Mödinger Y, Bahney CS, Marcucio RS, Miclau T, Ignatius A, Reber SO

The Society for Craniofacial Genetics and Developmental Biology 41st Annual Meeting.

American journal of medical genetics. Part A

Taneyhill LA, Moody SA, Cox T, Klein OD, Marcucio R, Schneider RA, Trainor PA

The Cellular Biology of Fracture Healing.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Bahney CS, Zondervan RL, Allison P, Theologis A, Ashley J, Ahn J, Miclau T, Marcucio R, Hankenson KD

The Developmental-Genetics of Canalization.

Seminars in cell & developmental biology

Hallgrimsson B, Green RM, Katz D, Fish JL, Bernier FPJ, Roseman CC, Young NM, Cheverud JM, Marcucio RS

Microenvironmental Regulation of Chondrocyte Plasticity in Endochondral Repair-A New Frontier for Developmental Engineering.

Frontiers in bioengineering and biotechnology

Wong SA, Rivera KO, Miclau T, Alsberg E, Marcucio RS, Bahney CS

The Society for Craniofacial Genetics and Developmental Biology 40th annual meeting.

American journal of medical genetics. Part A

Gammill L, Cox T, Moody S, Taneyhill L, Trainor P, Marcucio R

Simulation enabled search for explanatory mechanisms of the fracture healing process.

PLoS computational biology

Kennedy RC, Marmor M, Marcucio R, Hunt CA

Living tissues are more than cell clusters: The extracellular matrix as a driving force in morphogenesis.

Progress in biophysics and molecular biology

Linde-Medina M, Marcucio R

Developmental constraint through negative pleiotropy in the zygomatic arch.

EvoDevo

Percival CJ, Green R, Roseman CC, Gatti DM, Morgan JL, Murray SA, Donahue LR, Mayeux JM, Pollard KM, Hua K, Pomp D, Marcucio R, Hallgrímsson B

Developmental nonlinearity drives phenotypic robustness.

Nature communications

Green RM, Fish JL, Young NM, Smith FJ, Roberts B, Dolan K, Choi I, Leach CL, Gordon P, Cheverud JM, Roseman CC, Williams TJ, Marcucio RS, Hallgrímsson B

Effects of Aging on Fracture Healing.

Current osteoporosis reports

Clark D, Nakamura M, Miclau T, Marcucio R

Reverse engineering development: Crosstalk opportunities between developmental biology and tissue engineering.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Marcucio RS, Qin L, Alsberg E, Boerckel JD

Stimulating Fracture Healing in Ischemic Environments: Does Oxygen Direct Stem Cell Fate during Fracture Healing?

Frontiers in cell and developmental biology

Miclau KR, Brazina SA, Bahney CS, Hankenson KD, Hunt TK, Marcucio RS, Miclau T

Shaping the sound of voice.

eLife

Marcucio R

Craniofacial diversification in the domestic pigeon and the evolution of the avian skull.

Nature ecology & evolution

Young NM, Linde-Medina M, Fondon JW, Hallgrímsson B, Marcucio RS

Quantifying three-dimensional morphology and RNA from individual embryos.

Developmental dynamics : an official publication of the American Association of Anatomists

Green RM, Leach CL, Hoehn N, Marcucio RS, Hallgrímsson B

The society for craniofacial genetics and developmental biology 39th annual meeting.

American journal of medical genetics. Part A

Fish JL, Albertson C, Harris MP, Lozanoff S, Marcucio RS, Richtsmeier JT, Trainor PA

Development Shapes a Consistent Inbreeding Effect in Mouse Crania of Different Line Crosses.

Journal of experimental zoology. Part B, Molecular and developmental evolution

Pavlicev M, Mitteroecker P, Gonzalez PM, Rolian C, Jamniczky H, Villena FP, Marcucio R, Spritz R, Hallgrimsson B

Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes.

Development (Cambridge, England)

Hu DP, Ferro F, Yang F, Taylor AJ, Chang W, Miclau T, Marcucio RS, Bahney CS

Future Treatment Strategies for Delayed Bone Healing: An Osteoimmunologic Approach.

The Journal of the American Academy of Orthopaedic Surgeons

Schmidt-Bleek K, Marcucio R, Duda G

FGFR-associated craniosynostosis syndromes and gastrointestinal defects.

American journal of medical genetics. Part A

Hibberd CE, Bowdin S, Arudchelvan Y, Forrest CR, Brakora KA, Marcucio RS, Gong SG

Genetic structure of phenotypic robustness in the collaborative cross mouse diallel panel.

Journal of evolutionary biology

Gonzalez PN, Pavlicev M, Mitteroecker P, Pardo-Manuel de Villena F, Spritz RA, Marcucio RS, Hallgrímsson B

The society for craniofacial genetics and developmental biology 38th annual meeting.

American journal of medical genetics. Part A

Taneyhill LA, Hoover-Fong J, Lozanoff S, Marcucio R, Richtsmeier JT, Trainor PA

Facial surface morphology predicts variation in internal skeletal shape.

American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics

Young NM, Sherathiya K, Gutierrez L, Nguyen E, Bekmezian S, Huang JC, Hallgrímsson B, Lee JS, Marcucio RS

Promoting Endochondral Bone Repair Using Human Osteoarthritic Articular Chondrocytes.

Tissue engineering. Part A

Bahney CS, Jacobs L, Tamai R, Hu D, Luan TF, Wang M, Reddy S, Park M, Limburg S, Kim HT, Marcucio R, Kuo AC

Beyond cell proliferation in avian facial morphogenesis.

Developmental dynamics : an official publication of the American Association of Anatomists

Linde-Medina M, Hallgrímsson B, Marcucio R

Stem Cell Therapies in Orthopaedic Trauma.

Journal of orthopaedic trauma

Marcucio RS, Nauth A, Giannoudis PV, Bahney C, Piuzzi NS, Muschler G, Miclau T

Tissue engineering strategies for promoting vascularized bone regeneration.

Bone

Almubarak S, Nethercott H, Freeberg M, Beaudon C, Jha A, Jackson W, Marcucio R, Miclau T, Healy K, Bahney C

Morphometrics, 3D Imaging, and Craniofacial Development.

Current topics in developmental biology

Hallgrimsson B, Percival CJ, Green R, Young NM, Mio W, Marcucio R

Facial Morphogenesis: Physical and Molecular Interactions Between the Brain and the Face.

Current topics in developmental biology

Marcucio R, Hallgrimsson B, Young NM

Genetics of murine craniofacial morphology: diallel analysis of the eight founders of the Collaborative Cross.

Journal of anatomy

Percival CJ, Liberton DK, Pardo-Manuel de Villena F, Spritz R, Marcucio R, Hallgrímsson B

Correlations Between the Morphology of Sonic Hedgehog Expression Domains and Embryonic Craniofacial Shape.

Evolutionary biology

Xu Q, Jamniczky H, Hu D, Green RM, Marcucio RS, Hallgrimsson B, Mio W

Signals from the brain induce variation in avian facial shape.

Developmental dynamics : an official publication of the American Association of Anatomists

Hu D, Young NM, Xu Q, Jamniczky H, Green RM, Mio W, Marcucio RS, Hallgrimsson B

Divergence of craniofacial developmental trajectories among avian embryos.

Developmental dynamics : an official publication of the American Association of Anatomists

Smith FJ, Percival CJ, Young NM, Hu D, Schneider RA, Marcucio RS, Hallgrimsson B

Role of muscle stem cells during skeletal regeneration.

Stem cells (Dayton, Ohio)

Abou-Khalil R, Yang F, Lieu S, Julien A, Perry J, Pereira C, Relaix F, Miclau T, Marcucio R, Colnot C

A comparative examination of odontogenic gene expression in both toothed and toothless amniotes.

Journal of experimental zoology. Part B, Molecular and developmental evolution

Lainoff AJ, Moustakas-Verho JE, Hu D, Kallonen A, Marcucio RS, Hlusko LJ

The multifaceted role of the vasculature in endochondral fracture repair.

Frontiers in endocrinology

Bahney CS, Hu DP, Miclau T, Marcucio RS

A dynamic Shh expression pattern, regulated by SHH and BMP signaling, coordinates fusion of primordia in the amniote face.

Development (Cambridge, England)

Hu D, Young NM, Li X, Xu Y, Hallgrímsson B, Marcucio RS

Impact of retinoic acid exposure on midfacial shape variation and manifestation of holoprosencephaly in Twsg1 mutant mice.

Disease models & mechanisms

Billington CJ, Schmidt B, Marcucio RS, Hallgrimsson B, Gopalakrishnan R, Petryk A

Tfap2a-dependent changes in mouse facial morphology result in clefting that can be ameliorated by a reduction in Fgf8 gene dosage.

Disease models & mechanisms

Green RM, Feng W, Phang T, Fish JL, Li H, Spritz RA, Marcucio RS, Hooper J, Jamniczky H, Hallgrímsson B, Williams T

Let's face it--complex traits are just not that simple.

PLoS genetics

Hallgrimsson B, Mio W, Marcucio RS, Spritz R

Surface landmark quantification of embryonic mouse craniofacial morphogenesis.

BMC developmental biology

Percival CJ, Green R, Marcucio R, Hallgrímsson B

Biological perspectives of delayed fracture healing.

Injury

Hankenson KD, Zimmerman G, Marcucio R

Embryonic bauplans and the developmental origins of facial diversity and constraint.

Development (Cambridge, England)

Young NM, Hu D, Lainoff AJ, Smith FJ, Diaz R, Tucker AS, Trainor PA, Schneider RA, Hallgrímsson B, Marcucio RS

Delayed bone regeneration is linked to chronic inflammation in murine muscular dystrophy.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

Abou-Khalil R, Yang F, Mortreux M, Lieu S, Yu YY, Wurmser M, Pereira C, Relaix F, Miclau T, Marcucio RS, Colnot C

Modulation of macrophage activity during fracture repair has differential effects in young adult and elderly mice.

Journal of orthopaedic trauma

Slade Shantz JA, Yu YY, Andres W, Miclau T, Marcucio R

Stem cell-derived endochondral cartilage stimulates bone healing by tissue transformation.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

Bahney CS, Hu DP, Taylor AJ, Ferro F, Britz HM, Hallgrimsson B, Johnstone B, Miclau T, Marcucio RS

Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model.

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society

Demirkiran G, Dede O, Yalcin N, Akel I, Marcucio R, Acaroglu E

The effect of hypoxia on facial shape variation and disease phenotypes in chicken embryos.

Disease models & mechanisms

Smith F, Hu D, Young NM, Lainoff AJ, Jamniczky HA, Maltepe E, Hallgrimsson B, Marcucio RS

Disruption of thrombospondin-2 accelerates ischemic fracture healing.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Miedel E, Dishowitz MI, Myers MH, Dopkin D, Yu YY, Miclau TS, Marcucio R, Ahn J, Hankenson KD

Fgf8 dosage determines midfacial integration and polarity within the nasal and optic capsules.

Developmental biology

Griffin JN, Compagnucci C, Hu D, Fish J, Klein O, Marcucio R, Depew MJ

The role of oxygen during fracture healing.

Bone

Lu C, Saless N, Wang X, Sinha A, Decker S, Kazakia G, Hou H, Williams B, Swartz HM, Hunt TK, Miclau T, Marcucio RS

MMP9 regulates the cellular response to inflammation after skeletal injury.

Bone

Wang X, Yu YY, Lieu S, Yang F, Lang J, Lu C, Werb Z, Hu D, Miclau T, Marcucio R, Colnot C

The generation of variation and the developmental basis for evolutionary novelty.

Journal of experimental zoology. Part B, Molecular and developmental evolution

Hallgrímsson B, Jamniczky HA, Young NM, Rolian C, Schmidt-Ott U, Marcucio RS

Anti-inflammatory treatment increases angiogenesis during early fracture healing.

Archives of orthopaedic and trauma surgery

Lu C, Xing Z, Wang X, Mao J, Marcucio RS, Miclau T

Neural crest cells pattern the surface cephalic ectoderm during FEZ formation.

Developmental dynamics : an official publication of the American Association of Anatomists

Hu D, Marcucio RS

The metabolic basis of adolescent idiopathic scoliosis: 2011 report of the "metabolic" workgroup of the Fondation Yves Cotrel.

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society

Acaroglu E, Bobe R, Enouf J, Marcucio R, Moldovan F, Moreau A

Signaling by SHH rescues facial defects following blockade in the brain.

Developmental dynamics : an official publication of the American Association of Anatomists

Chong HJ, Young NM, Hu D, Jeong J, McMahon AP, Hallgrimsson B, Marcucio RS

Vascular endothelial growth factor improves bone repair in a murine nonunion model.

The Iowa orthopaedic journal

Ogilvie CM, Lu C, Marcucio R, Lee M, Thompson Z, Hu D, Helms JA, Miclau T

Is decreased bone mineral density associated with development of scoliosis? A bipedal osteopenic rat model.

Scoliosis

Dede O, Akel I, Demirkiran G, Yalcin N, Marcucio R, Acaroglu E

Epigenetic integration of the developing brain and face.

Developmental dynamics : an official publication of the American Association of Anatomists

Parsons TE, Schmidt EJ, Boughner JC, Jamniczky HA, Marcucio RS, Hallgrímsson B

Mechanical stability affects angiogenesis during early fracture healing.

Journal of orthopaedic trauma

Lu C, Saless N, Hu D, Wang X, Xing Z, Hou H, Williams B, Swartz HM, Colnot C, Miclau T, Marcucio RS

Structured three-dimensional co-culture of mesenchymal stem cells with chondrocytes promotes chondrogenic differentiation without hypertrophy.

Osteoarthritis and cartilage

Cooke ME, Allon AA, Cheng T, Kuo AC, Kim HT, Vail TP, Marcucio RS, Schneider RA, Lotz JC, Alliston T

Assessing signaling properties of ectodermal epithelia during craniofacial development.

Journal of visualized experiments : JoVE

Hu D, Marcucio RS

Mechanisms that underlie co-variation of the brain and face.

Genesis (New York, N.Y. : 2000)

Marcucio RS, Young NM, Hu D, Hallgrimsson B

Impaired remodeling phase of fracture repair in the absence of matrix metalloproteinase-2.

Disease models & mechanisms

Lieu S, Hansen E, Dedini R, Behonick D, Werb Z, Miclau T, Marcucio R, Colnot C

Quantitative analyses link modulation of sonic hedgehog signaling to continuous variation in facial growth and shape.

Development (Cambridge, England)

Young NM, Chong HJ, Hu D, Hallgrímsson B, Marcucio RS

Trauma-induced inflammation and fracture healing.

Journal of orthopaedic trauma

Pape HC, Marcucio R, Humphrey C, Colnot C, Knobe M, Harvey EJ

Rejuvenation of the inflammatory system stimulates fracture repair in aged mice.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Xing Z, Lu C, Hu D, Miclau T, Marcucio RS

Action of IL-1beta during fracture healing.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Lange J, Sapozhnikova A, Lu C, Hu D, Li X, Miclau T, Marcucio RS

Recombinant human bone morphogenetic protein-7 enhances fracture healing in an ischemic environment.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Lu C, Xing Z, Yu YY, Colnot C, Miclau T, Marcucio RS

Multiple roles for CCR2 during fracture healing.

Disease models & mechanisms

Xing Z, Lu C, Hu D, Yu YY, Wang X, Colnot C, Nakamura M, Wu Y, Miclau T, Marcucio RS

Absence of beta3 integrin accelerates early skeletal repair.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Hu D, Lu C, Sapozhnikova A, Barnett M, Sparrey C, Miclau T, Marcucio RS

Deciphering the Palimpsest: Studying the Relationship Between Morphological Integration and Phenotypic Covariation.

Evolutionary biology

Hallgrímsson B, Jamniczky H, Young NM, Rolian C, Parsons TE, Boughner JC, Marcucio RS

Basic research in orthopedic surgery: Current trends and future directions.

Indian journal of orthopaedics

Lu C, Buckley JM, Colnot C, Marcucio R, Miclau T

The effect of calmodulin antagonists on experimental scoliosis: a pinealectomized chicken model.

Spine

Akel I, Kocak O, Bozkurt G, Alanay A, Marcucio R, Acaroglu E

The effect of calmodulin antagonists on scoliosis: bipedal C57BL/6 mice model.

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society

Akel I, Demirkiran G, Alanay A, Karahan S, Marcucio R, Acaroglu E

Effect of bone morphogenetic protein signaling on development of the jaw skeleton.

Developmental dynamics : an official publication of the American Association of Anatomists

Hu D, Colnot C, Marcucio RS

Effect of age on vascularization during fracture repair.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Lu C, Hansen E, Sapozhnikova A, Hu D, Miclau T, Marcucio RS

Tibial fracture decreases oxygen levels at the site of injury.

The Iowa orthopaedic journal

Lu C, Rollins M, Hou H, Swartz HM, Hopf H, Miclau T, Marcucio RS

Effects of delayed stabilization on fracture healing.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Miclau T, Lu C, Thompson Z, Choi P, Puttlitz C, Marcucio R, Helms JA

Role of matrix metalloproteinase 13 in both endochondral and intramembranous ossification during skeletal regeneration.

PloS one

Behonick DJ, Xing Z, Lieu S, Buckley JM, Lotz JC, Marcucio RS, Werb Z, Miclau T, Colnot C

Ischemia leads to delayed union during fracture healing: a mouse model.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Lu C, Miclau T, Hu D, Marcucio RS

Patterns of infantile hemangiomas: new clues to hemangioma pathogenesis and embryonic facial development.

Pediatrics

Haggstrom AN, Lammer EJ, Schneider RA, Marcucio R, Frieden IJ

Assessing angiogenesis during fracture healing.

The Iowa orthopaedic journal

Lu C, Marcucio R, Miclau T

Molecular interactions coordinating the development of the forebrain and face.

Developmental biology

Marcucio RS, Cordero DR, Hu D, Helms JA

Cellular basis for age-related changes in fracture repair.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

Lu C, Miclau T, Hu D, Hansen E, Tsui K, Puttlitz C, Marcucio RS

The Collaborative Cross, a community resource for the genetic analysis of complex traits.

Nature genetics

Churchill GA, Airey DC, Allayee H, Angel JM, Attie AD, Beatty J, Beavis WD, Belknap JK, Bennett B, Berrettini W, Bleich A, Bogue M, Broman KW, Buck KJ, Buckler E, Burmeister M, Chesler EJ, Cheverud JM, Clapcote S, Cook MN, Cox RD, Crabbe JC, Crusio WE, Darvasi A, Deschepper CF, Doerge RW, Farber CR, Forejt J, Gaile D, Garlow SJ, Geiger H, Gershenfeld H, Gordon T, Gu J, Gu W, de Haan G, Hayes NL, Heller C, Himmelbauer H, Hitzemann R, Hunter K, Hsu HC, Iraqi FA, Ivandic B, Jacob HJ, Jansen RC, Jepsen KJ, Johnson DK, Johnson TE, Kempermann G, Kendziorski C, Kotb M, Kooy RF, Llamas B, Lammert F, Lassalle JM, Lowenstein PR, Lu L, Lusis A, Manly KF, Marcucio R, Matthews D, Medrano JF, Miller DR, Mittleman G, Mock BA, Mogil JS, Montagutelli X, Morahan G, Morris DG, Mott R, Nadeau JH, Nagase H, Nowakowski RS, O'Hara BF, Osadchuk AV, Page GP, Paigen B, Paigen K, Palmer AA, Pan HJ, Peltonen-Palotie L, Peirce J, Pomp D, Pravenec M, Prows DR, Qi Z, Reeves RH, Roder J, Rosen GD, Schadt EE, Schalkwyk LC, Seltzer Z, Shimomura K, Shou S, Sillanpää MJ, Siracusa LD, Snoeck HW, Spearow JL, Svenson K, Tarantino LM, Threadgill D, Toth LA, Valdar W, de Villena FP, Warden C, Whatley S, Williams RW, Wiltshire T, Yi N, Zhang D, Zhang M, Zou F

Temporal perturbations in sonic hedgehog signaling elicit the spectrum of holoprosencephaly phenotypes.

The Journal of clinical investigation

Cordero D, Marcucio R, Hu D, Gaffield W, Tapadia M, Helms JA

Morphogenesis of blood vessels in the head muscles of avian embryo: spatial, temporal, and VEGF expression analyses.

Developmental dynamics : an official publication of the American Association of Anatomists

Ruberte J, Carretero A, Navarro M, Marcucio RS, Noden D

A zone of frontonasal ectoderm regulates patterning and growth in the face.

Development (Cambridge, England)

Hu D, Marcucio RS, Helms JA

Prenatal morphogenesis of the human mental foramen.

European journal of oral sciences

Radlanski RJ, Renz H, Müller U, Schneider RS, Marcucio RS, Helms JA

Differentiation of avian craniofacial muscles: I. Patterns of early regulatory gene expression and myosin heavy chain synthesis.

Developmental dynamics : an official publication of the American Association of Anatomists

Noden DM, Marcucio R, Borycki AG, Emerson CP

Myotube heterogeneity in developing chick craniofacial skeletal muscles.

Developmental dynamics : an official publication of the American Association of Anatomists

Marcucio RS, Noden DM

In vitro interaction between oviduct epithelial and equine sperm.

Archives of andrology

Ellington JE, Ignotz GG, Varner DD, Marcucio RS, Mathison P, Ball BA