Bio


Peter is an Inpatient Urology Nurse Practitioner joining the Urology team in 2019. He graduated from The Ohio State University in 2017 with a Master’s of Science in Nursing in Adult-Gerontology Acute Care. He has also worked as a perioperative RN for 4 years at The James Comprehensive Cancer Center in Columbus, OH getting surgical oncology patients ready for surgery and recovering them afterward. Prior to his career as a nurse, Peter was a researcher studying cartilage development at the Cleveland Clinic that resulted in several publications.

Clinical Focus


  • Nurse Practitioner

Professional Education


  • Board Certification: American Nurses Credentialing Center, Nurse Practitioner (2017)
  • Professional Education: The Ohio State University Registrar (2017) OH

All Publications


  • Sox9 Directs Hypertrophic Maturation and Blocks Osteoblast Differentiation of Growth Plate Chondrocytes DEVELOPMENTAL CELL Dy, P., Wang, W., Bhattaram, P., Wang, Q., Wang, L., Ballock, R., Lefebvre, V. 2012; 22 (3): 597–609

    Abstract

    The transcription factor Sox9 is necessary for early chondrogenesis, but its subsequent roles in the cartilage growth plate, a highly specialized structure that drives skeletal growth and endochondral ossification, remain unclear. Using a doxycycline-inducible Cre transgene and Sox9 conditional null alleles in the mouse, we show that Sox9 is required to maintain chondrocyte columnar proliferation and generate cell hypertrophy, two key features of functional growth plates. Sox9 keeps Runx2 expression and β-catenin signaling in check and thereby inhibits not only progression from proliferation to prehypertrophy, but also subsequent acquisition of an osteoblastic phenotype. Sox9 protein outlives Sox9 RNA in upper hypertrophic chondrocytes, where it contributes with Mef2c to directly activate the major marker of these cells, Col10a1. These findings thus reveal that Sox9 remains a central determinant of the lineage fate and multistep differentiation program of growth plate chondrocytes and thereby illuminate our understanding of key molecular mechanisms underlying skeletogenesis.

    View details for DOI 10.1016/j.devcel.2011.12.024

    View details for Web of Science ID 000301701600014

    View details for PubMedID 22421045

    View details for PubMedCentralID PMC3306603

  • Sox6 Is Necessary for Efficient Erythropoiesis in Adult Mice under Physiological and Anemia-Induced Stress Conditions PLOS ONE Dumitriu, B., Bhattaram, P., Dy, P., Huang, Y., Quayum, N., Jensen, J., Lefebvre, V. 2010; 5 (8): e12088

    Abstract

    Definitive erythropoiesis is a vital process throughout life. Both its basal activity under physiological conditions and its increased activity under anemia-induced stress conditions are highly stimulated by the hormone erythropoietin. The transcription factor Sox6 was previously shown to enhance fetal erythropoiesis together and beyond erythropoietin signaling, but its importance in adulthood and mechanisms of action remain unknown. We used here Sox6 conditional null mice and molecular assays to address these questions.Sox6fl/flErGFPCre adult mice, which lacked Sox6 in erythroid cells, exhibited compensated anemia, erythroid cell developmental defects, and anisocytotic, short-lived red cells under physiological conditions, proving that Sox6 promotes basal erythropoiesis. Tamoxifen treatment of Sox6fl/flCaggCreER mice induced widespread inactivation of Sox6 in a timely controlled manner and resulted in erythroblast defects before reticulocytosis, demonstrating that impaired erythropoiesis is a primary cause rather than consequence of anemia in the absence of Sox6. Twenty five percent of Sox6fl/flErGFPCre mice died 4 or 5 days after induction of acute anemia with phenylhydrazine. The others recovered slowly. They promptly increased their erythropoietin level and amplified their erythroid progenitor pool, but then exhibited severe erythroblast and reticulocyte defects. Sox6 is thus essential in the maturation phase of stress erythropoiesis that follows the erythropoietin-dependent amplification phase. Sox6 inactivation resulted in upregulation of embryonic globin genes, but embryonic globin chains remained scarce and apparently inconsequential. Sox6 inactivation also resulted in downregulation of erythroid terminal markers, including the Bcl2l1 gene for the anti-apoptotic factor Bcl-xL, and in vitro assays indicated that Sox6 directly upregulates Bcl2l1 downstream of and beyond erythropoietin signaling.This study demonstrates that Sox6 is necessary for efficient erythropoiesis in adult mice under both basal and stress conditions. It is primarily involved in enhancing the survival rate and maturation process of erythroid cells and acts at least in part by upregulating Bcl2l1.

    View details for DOI 10.1371/journal.pone.0012088

    View details for Web of Science ID 000280776800020

    View details for PubMedID 20711497

    View details for PubMedCentralID PMC2918505

  • Synovial joint morphogenesis requires the chondrogenic action of Sox5 and Sox6 in growth plate and articular cartilage DEVELOPMENTAL BIOLOGY Dy, P., Smits, P., Silvester, A., Penzo-Mendez, A., Dumitriu, B., Han, Y., de la Motte, C. A., Kingsley, D. M., Lefebvre, V. 2010; 341 (2): 346-359

    Abstract

    The mechanisms underlying synovial joint development remain poorly understood. Here we use complete and cell-specific gene inactivation to identify the roles of the redundant chondrogenic transcription factors Sox5 and Sox6 in this process. We show that joint development aborts early in complete mutants (Sox5(-/-)6(-/-)). Gdf5 and Wnt9a expression is punctual in articular progenitor cells, but Sox9 downregulation and cell condensation in joint interzones are late. Joint cell differentiation is unsuccessful, regardless of lineage, and cavitation fails. Sox5 and Sox6 restricted expression to chondrocytes in wild-type embryos and continued Erg expression and weak Ihh expression in Sox5(-/-)6(-/-) growth plates suggest that growth plate failure contribute to this Sox5(-/-)6(-/-) joint morphogenesis block. Sox5/6 inactivation in specified joint cells and chondrocytes (Sox5(fl/fl)6(fl/fl)Col2Cre) also results in a joint morphogenesis block, whereas Sox5/6 inactivation in specified joint cells only (Sox5(fl/fl)6(fl/fl)Gdf5Cre) results in milder joint defects and normal growth plates. Sox5(fl/fl)6(fl/fl)Gdf5Cre articular chondrocytes remain undifferentiated, as shown by continued Gdf5 expression and pancartilaginous gene downregulation. Along with Prg4 downregulation, these defects likely account for joint tissue overgrowth and incomplete cavitation in adult mice. Together, these data suggest that synovial joint morphogenesis relies on essential roles for Sox5/6 in promoting both growth plate and articular chondrocyte differentiation.

    View details for DOI 10.1016/j.ydbio.2010.02.024

    View details for Web of Science ID 000277404300002

    View details for PubMedID 20206616

    View details for PubMedCentralID PMC2862098

  • Generation of mice harboring a Sox5 conditional null allele GENESIS Dy, P., Huan, Y., Lefebvre, V. 2008; 46 (6): 294–99

    Abstract

    Sox5 belongs to the Sry-related HMG box gene family, which encodes transcription factors controlling cell fate and differentiation in many lineages. Sox5 produces a long L-Sox5 protein in neuronal, glial, neural crest, cartilage, and other cells, and a short Sox5 protein in spermatids. Sox5(-/-) mice have revealed essential roles for L-Sox5 in development but their neonatal death has prevented postnatal studies. We show here that we have generated mice harboring a conditional null allele for L-Sox5 (Sox5(fl+)) by flanking the fifth coding exon with loxP sites. Cre recombinase-mediated conversion of Sox5(fl+) into Sox5(fl-) abolishes L-Sox5 expression. Expectedly, Sox5(fl+/fl+) mice are indistinguishable from wildtype mice, and Sox5(fl-/fl-) mice from Sox5(-/-) mice. Moreover, the chondrodysplasia of Sox5(fl+/fl+)Sox6(fl+/fl+)Prx1Cre mice demonstrates that the two redundant chondrogenic Sox genes can be efficiently inactivated in a cell type-specific manner. This Sox5 conditional null allele will be valuable in further uncovering the in vivo roles of L-Sox5.

    View details for DOI 10.1002/dvg.20392

    View details for Web of Science ID 000257480900003

    View details for PubMedID 18543318

  • The three SoxC proteinsSox4, Sox11 and Sox12-exhibit overlapping expression patterns and molecular properties NUCLEIC ACIDS RESEARCH Dy, P., Penzo-Mendez, A., Wang, H., Pedraza, C. E., Macklin, W. B., Lefebvre, V. 2008; 36 (9): 3101–17

    Abstract

    The group C of Sry-related high-mobility group (HMG) box (Sox) transcription factors has three members in most vertebrates: Sox4, Sox11 and Sox12. Sox4 and Sox11 have key roles in cardiac, neuronal and other major developmental processes, but their molecular roles in many lineages and the roles of Sox12 remain largely unknown. We show here that the three genes are co-expressed at high levels in neuronal and mesenchymal tissues in the developing mouse, and at variable relative levels in many other tissues. The three proteins have conserved remarkable identity through evolution in the HMG box DNA-binding domain and in the C-terminal 33 residues, and we demonstrate that the latter residues constitute their transactivation domain (TAD). Sox11 activates transcription several times more efficiently than Sox4 and up to one order of magnitude more efficiently than Sox12, owing to a more stable alpha-helical structure of its TAD. This domain and acidic domains interfere with DNA binding, Sox11 being most affected and Sox4 least affected. The proteins are nevertheless capable of competing with one another in reporter gene transactivation. We conclude that the three SoxC proteins have conserved overlapping expression patterns and molecular properties, and might therefore act in concert to fulfill essential roles in vivo.

    View details for DOI 10.1093/nar/gkn162

    View details for Web of Science ID 000256173200035

    View details for PubMedID 18403418

    View details for PubMedCentralID PMC2396431

  • Generation of mice harboring a Sox4 conditional null allele GENESIS Penzo-Mendez, A., Dy, P., Pallavi, B., Lefebvre, V. 2007; 45 (12): 776–80

    Abstract

    Sox4 belongs to the family of Sry-related HMG box transcription factors, which specify cell fate and differentiation in many lineages. Sox4 is widely expressed in the embryo and controls such processes as neuronal tissue, lymphocyte, heart, and bone development. Sox4-null mice die at embryonic day 14 from heart malformation. This early lethality has therefore limited studies on Sox4 functions. We show here that we have generated mice harboring a Sox4 conditional null allele (Sox4fl+) by flanking the entire coding region with loxP sites. Sox4fl+/fl+ mice are indistinguishable from wildtype mice and produce the wildtype Sox4 protein at a normal level. Sox4fl+ is efficiently converted into a null allele (Sox4fl-) by Cre recombinase in somatic and germ-line cells, and Sox4fl-/fl- embryos die from the same heart defects as Sox4-/- mice. This Sox4 conditional null allele will thus be a valuable tool to further uncovering Sox4 functions in various processes in vivo.

    View details for DOI 10.1002/dvg.20358

    View details for Web of Science ID 000252307200007

    View details for PubMedID 18064674

  • Generation of mice harboring a Sox6 conditional null allele GENESIS Dumitriu, B., Dy, P., Smits, P., Lefebvre, V. 2006; 44 (5): 219–24

    Abstract

    Sox6 belongs to the family of Sry-related HMG box transcription factors, which determine cell fate and differentiation in various lineages. Sox6 is expressed in several tissues, including cartilage, testis, neuronal, and erythropoietic tissues. Mice lacking Sox6 have revealed critical roles for Sox6 in several of these tissues, but their multiple defects and early lethality has limited studies in specific cell types and in postnatal mice. We show here that we have generated mice harboring a Sox6 conditional null allele (Sox6(fl+)) by flanking the second coding exon with loxP sites. This allele encodes wildtype Sox6 protein, is expressed normally, and is efficiently converted into a null allele (Sox6(fl-)) by Cre-mediated recombination in somatic and germ cells. Sox6(fl+/fl+) mice are indistinguishable from wildtype mice, and Sox6(fl-/fl-) mice from Sox6(-/-) mice. These Sox6 conditional null mice will thus be valuable for further uncovering the roles of Sox6 in various processes in vivo.

    View details for DOI 10.1002/dvg.20210

    View details for Web of Science ID 000238034300001

    View details for PubMedID 16652367

  • Sox5 and Sox6 are needed to develop and maintain source, columnar, and hypertrophic chondrocytes in the cartilage growth plate JOURNAL OF CELL BIOLOGY Smits, P., Dy, P., Mitra, S., Lefebvre 2004; 164 (5): 747–58

    Abstract

    Sox5 and Sox6 encode Sry-related transcription factors that redundantly promote early chondroblast differentiation. Using mouse embryos with three or four null alleles of Sox5 and Sox6, we show that they are also essential and redundant in major steps of growth plate chondrocyte differentiation. Sox5 and Sox6 promote the development of a highly proliferating pool of chondroblasts between the epiphyses and metaphyses of future long bones. This pool is the likely cellular source of growth plates. Sox5 and Sox6 permit formation of growth plate columnar zones by keeping chondroblasts proliferating and by delaying chondrocyte prehypertrophy. They allow induction of chondrocyte hypertrophy and permit formation of prehypertrophic and hypertrophic zones by delaying chondrocyte terminal differentiation induced by ossification fronts. They act, at least in part, by down-regulating Ihh signaling, Fgfr3, and Runx2 and by up-regulating Bmp6. In conclusion, Sox5 and Sox6 are needed for the establishment of multilayered growth plates, and thereby for proper and timely development of endochondral bones.

    View details for DOI 10.1083/jcb.200312045

    View details for Web of Science ID 000220050800013

    View details for PubMedID 14993235

    View details for PubMedCentralID PMC2172159