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Stephen Harris, Ph.D.
Dental School
Periodontics
210-567-3723
harris@uthscsa.edu
Dr. Stephen Harris' lab is interested in various aspects of gene regulation since 1965. Working in Dr. Bert O’Malley lab, he proved that estrogen induced the ovalbumin gene at the mRNA level in 1974. He has worked on various aspects of gene regulation by growth factors and androgens since that time.
In 1990, he began his studies of bone and teeth with Dr. Greg Mundy in San Antonio TX, and a focus on the Bmp2 and Bmp4 genes. During that time, he also worked with Stuart Kauffman on computational and theoretical models of gene regulation at the transcription level. In 1999, he began various systems biology approaches in the lab to study large sets of gene expression pattern with microarrays and regulation by Bmp2 in osteoblast models.
With his interest in system biology and gene network approaches, he has spent the past two years relearning Unix commands and simple programming with the help of several computer experts here at the UTHSCSA. Our university has made a major investment in expanding our next generation sequencing hardware and bioinformatics tools and he is directly helping in that effort. With Dr. Bo Demeler, we now have a supercomputer with over 500 nodes that he routinely uses to analyze any of the NGS sequence files, with the software packages and our own scripts we have installed on this supercomputer. The bioinformatics tools and databases at GEO and elsewhere now make this one of the most exciting areas in medicine and biology.
Bone and Periodontal stem cells, epigenomica, lineage tracing, and conditional KO studies in mice with the Bmp2 and Sost genes Research
Sub-Field of Study: Bioinformatics with specialty in epigenomics and transcriptomics
Techniques Used: conditional ko studies, with uct, sem, high resolution x-rays, histology, rna-seq analysis with the Alamo supercomputer, confocal and image analysis
Education
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| Year | Degree | Discipline | Institution |
| 1969 | PhD | Biochemical Embryology | University of Texas Austin , TX |
| 1969 | PhD | Biochemical Embryology | University of Texas Austin , TX |
| 1966 | MA | Biochemical Genetics | University of Texas Austin , TX |
| 1966 | MA | Biochemical Genetics | University of Texas Austin , TX |
| 1965 | BA | Zoology | University of Texas Austin , TX |
| 1965 | BA | Zoology | University of Texas Austin , TX |
| Postdoctoral Fellowship | California Institute of Technology Pasadena , CA | ||
| Postdoctoral Fellowship | California Institute of Technology Pasadena , CA | ||
| Residency | Vanderbilt University School of Medicine Nashville , TN | ||
| Residency | Vanderbilt University School of Medicine Nashville , TN |
Appointments
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| 1/2004 - Present | Professor and Director of Research | University of Texas Health Science Center at San Antonio, Periodontics, San Antonio, TX |
| 1/2004 - Present | Professor | University of Texas Health Science Center at San Antonio, Cellular & Structural Biology, San Antonio, TX |
| 1/2004 - Present | Professor | University of Texas Health Science Center at San Antonio, Cellular & Structural Biology, San Antonio, TX |
| 1/2004 - Present | Professor and Director of Research | University of Texas Health Science Center at San Antonio, Periodontics, San Antonio, TX |
Expertise
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BMP2 Mechanisms - Mechanisms of how BMP2 instructs cells to new differentiated functions during development and during bone and teeth formation. |
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BMP2 Mechanisms - Mechanisms of how BMP2 instructs cells to new differentiated functions during development and during bone and teeth formation. |
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Bone Morphogenetic Protein (BMP) Genes - Structure and functional analysis of bone morphogenetic protein (BMP) genes with focus on BMP2 and BMP4 genes. Develop condition knock-out of both BMP2 and BMP4 in osteoblasts using the Cre-loxP system and Tamoxifen temporal control of Cre activity. |
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Bone Morphogenetic Protein (BMP) Genes - Structure and functional analysis of bone morphogenetic protein (BMP) genes with focus on BMP2 and BMP4 genes. Develop condition knock-out of both BMP2 and BMP4 in osteoblasts using the Cre-loxP system and Tamoxifen temporal control of Cre activity. |
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Gene regulation and epigenomics - We study in skeletal stem cells and periodontal stem/stromal cells the mechanism of differentiation to various state, pdl, alveolar bone, cementums, osteocyte, and cementocytes using primary and clonal cell models and epigenomic states and enhancers that control gene expression. |
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Gene regulation and epigenomics - We study in skeletal stem cells and periodontal stem/stromal cells the mechanism of differentiation to various state, pdl, alveolar bone, cementums, osteocyte, and cementocytes using primary and clonal cell models and epigenomic states and enhancers that control gene expression. |
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Osteocyte Function - Analysis of osteocyte function in vitro and in vivo after mechanical loading. Genomic analysis of osteocyte gene expression signatures and gene regulatory networks. Cis regulatory analysis of osteocyte and mechanically responsive genes using BAC recombineering. |
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Osteocyte Function - Analysis of osteocyte function in vitro and in vivo after mechanical loading. Genomic analysis of osteocyte gene expression signatures and gene regulatory networks. Cis regulatory analysis of osteocyte and mechanically responsive genes using BAC recombineering. |
Publications
Abstract |
| Harris SE1, Rakian A1, Rediske M1, Neitske R1, Lee S1 , Kalajazic I 2 , Harris MA1, Gluhak ?Heinrich J1, and Yong C1. Periodontal Stem Cell Epigenomic and Gene Regulatory Network Analysis During Differentiation; 2019 Mar. (Keystone Symposium in Banff_Epigenetics and Human Disease). |
| Harris SE1, Rakian A1, Rediske M1, Neitske R1, Lee S1 , Kalajazic I 2 , Harris MA1, Gluhak ?Heinrich J1, and Yong C1. Periodontal Stem Cell Epigenomic and Gene Regulatory Network Analysis During Differentiation; 2019 Mar. (Keystone Symposium in Banff_Epigenetics and Human Disease). |
| Harris SE1, Rakian A1, Rediske M1, Neitske R1, Lee S1 , Bonewald LB2, Foster BL3, Harris MA1, Gluhak ?Heinrich J1, and Yong C1. Periodontal Stem Cell Differentiation: Transcriptome and Epigenetic Regulation at the Single Cell Level; 2018 Apr. (Keystone Symposium of Molecular and Cellular Biology_Gene Control in Development and Disease). |
| Harris SE1, Rakian A1, Rediske M1, Neitske R1, Lee S1 , Bonewald LB2, Foster BL3, Harris MA1, Gluhak ?Heinrich J1, and Yong C1. Periodontal Stem Cell Differentiation: Transcriptome and Epigenetic Regulation at the Single Cell Level; 2018 Apr. (Keystone Symposium of Molecular and Cellular Biology_Gene Control in Development and Disease). |
| Stephen E Harris1 ,Marie A. Harris1, J. Heinrich-Gluhak1, and Yong Cui1 . Bmp2 Regulation of Enhancer RNAs during Mesenchymal Stem Cell to Osteoblast-Osteocytes And Comparison to Limb In Vivo Enhancer Regions and IDGSW3 In Vitro Enhancer Regions During Differentiation; 2017 Apr. (Keystone Symposium of Molecular and Cellular Biology_Chromatin and Epigenetics). |
| Stephen E Harris1 ,Marie A. Harris1, J. Heinrich-Gluhak1, and Yong Cui1 . Bmp2 Regulation of Enhancer RNAs during Mesenchymal Stem Cell to Osteoblast-Osteocytes And Comparison to Limb In Vivo Enhancer Regions and IDGSW3 In Vitro Enhancer Regions During Differentiation; 2017 Apr. (Keystone Symposium of Molecular and Cellular Biology_Chromatin and Epigenetics). |
| SE Harris1, MA Harris, Coralee Tye, Ivo Kalajzic, J Gordon, J Lian, and G Stein. Candidate Enhancer RNA Expression During αSMA Progenitor to Mineralizing Osteoblasts-Osteocytes: Exploration of the `Dark Matter? of the Genome; 2015 Sep. (journal bone and mineral metabolism). |
| SE Harris1, MA Harris, Coralee Tye, Ivo Kalajzic, J Gordon, J Lian, and G Stein. Candidate Enhancer RNA Expression During αSMA Progenitor to Mineralizing Osteoblasts-Osteocytes: Exploration of the `Dark Matter? of the Genome; 2015 Sep. (journal bone and mineral metabolism). |
| Sharma R, Vanegas D, Victor D, Zhang Y, Lopez-Cruzan M, Woodruff K, Horn D, Fajardo RJ, Harris SE, Werner SL, Herman BA. A critical role for Caspase-2 in regulating osteoclast numbers in male age-related osteoporosis Minneapolis, MN; 2012 Oct. (J Bone Miner Res; vol. 27, no. Supp1). |
| Sharma R, Vanegas D, Victor D, Zhang Y, Lopez-Cruzan M, Woodruff K, Horn D, Fajardo RJ, Harris SE, Werner SL, Herman BA. A critical role for Caspase-2 in regulating osteoclast numbers in male age-related osteoporosis Minneapolis, MN; 2012 Oct. (J Bone Miner Res; vol. 27, no. Supp1). |
Book Chapter |
| Harris S. The Periodontium. In: Harris SE, Rakian A, Foster BL, Chun YP, and Rakian R. Principles of Bone Biology, 4th Edition. 2020. |
| Harris S. The Periodontium. In: Harris SE, Rakian A, Foster BL, Chun YP, and Rakian R. Principles of Bone Biology, 4th Edition. 2020. |
Journal Article |
| Maurel DB1,2, Matsumoto T3, Vallejo JA1, Johnson ML1, Dallas SL1, Kitase Y3, Brotto M4, Wacker MJ5, Harris MA6, Harris SE6, Bonewald LF1,3,7. Characterization of a novel murine Sost ERT2 Cre model targeting osteocytes Bone Research 2019 Feb;. |
| Maurel DB1,2, Matsumoto T3, Vallejo JA1, Johnson ML1, Dallas SL1, Kitase Y3, Brotto M4, Wacker MJ5, Harris MA6, Harris SE6, Bonewald LF1,3,7. Characterization of a novel murine Sost ERT2 Cre model targeting osteocytes Bone Research 2019 Feb;. |
| Davis HM1, Aref MW1, Aguilar-Perez A1, Pacheco-Costa R1, Allen K1, Valdez S1, Herrera C1, Atkinson EG1, Mohammad A1, Lopez D1, Harris MA2, Harris SE2, Allen M1, Bellido T1,3,4, Plotkin LI. Cx43 overexpression in osteocytes prevents osteocyte apoptosis and preserves cortical bone quality in aging mice JBMR Plus 2018 May;2(4). |
| Davis HM1, Aref MW1, Aguilar-Perez A1, Pacheco-Costa R1, Allen K1, Valdez S1, Herrera C1, Atkinson EG1, Mohammad A1, Lopez D1, Harris MA2, Harris SE2, Allen M1, Bellido T1,3,4, Plotkin LI. Cx43 overexpression in osteocytes prevents osteocyte apoptosis and preserves cortical bone quality in aging mice JBMR Plus 2018 May;2(4). |
| Jing Y1, Jing J2, Wang K3, Chan K3, Harris SE4, Hinton RJ3, Feng JQ3. Vital Roles of β-catenin in Trans-differentiation of Chondrocytes to Bone Cells int j Biol Sci 2018 Jan;. |
| Jing Y1, Jing J2, Wang K3, Chan K3, Harris SE4, Hinton RJ3, Feng JQ3. Vital Roles of β-catenin in Trans-differentiation of Chondrocytes to Bone Cells int j Biol Sci 2018 Jan;. |
| Jing Y, Jing J, Ye L, Liu X, Harris SE, Hinton RJ, Feng JQ. Chondrogenesis and osteogenesis are one continuous developmental and lineage defined biological process Scientific Reports 2017 Aug;7(1). |
| Jing Y, Jing J, Ye L, Liu X, Harris SE, Hinton RJ, Feng JQ. Chondrogenesis and osteogenesis are one continuous developmental and lineage defined biological process Scientific Reports 2017 Aug;7(1). |
| Wang J1,2, Massoudi D3, Ren Y1, Muir AM3, Harris SE4, Greenspan DS3, Feng JQ. BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis JDR 2017 May;96(5). |
| Wang J1,2, Massoudi D3, Ren Y1, Muir AM3, Harris SE4, Greenspan DS3, Feng JQ. BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis JDR 2017 May;96(5). |
| Zhang Q1, Lin S2, Liu Y3, Yuan B4, Harris SE5, Feng JQ. Dmp1 Null Mice Develop a Unique Osteoarthritis-like Phenotype Inr J Biol Sci 2016 Sep;12(10). |
| Zhang Q1, Lin S2, Liu Y3, Yuan B4, Harris SE5, Feng JQ. Dmp1 Null Mice Develop a Unique Osteoarthritis-like Phenotype Inr J Biol Sci 2016 Sep;12(10). |
| Ren Y1, Han X1, Ho SP2, Harris SE1, Cao Z1, Economides AN1, Qin C1, Ke H1, Liu M1, Feng JQ. Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model faseb j 2015 Jul;29(7). |
| Ren Y1, Han X1, Ho SP2, Harris SE1, Cao Z1, Economides AN1, Qin C1, Ke H1, Liu M1, Feng JQ. Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model faseb j 2015 Jul;29(7). |
| Prideaux M, Dallas SL, Zhao N, Johnsrud ED, Veno PA, Guo D, Mishina Y, Harris SE, Bonewald LF. Parathyroid Hormone Induces Bone Cell Motility and Loss of Mature Osteocyte Phenotype through L-Calcium Channel Dependent and Independent Mechanisms PLoS One 2015 May;10(5):0125731-0125731. |
| Prideaux M, Dallas SL, Zhao N, Johnsrud ED, Veno PA, Guo D, Mishina Y, Harris SE, Bonewald LF. Parathyroid Hormone Induces Bone Cell Motility and Loss of Mature Osteocyte Phenotype through L-Calcium Channel Dependent and Independent Mechanisms PLoS One 2015 May;10(5):0125731-0125731. |
| Guo F, Feng J, Wang F, Li W, Gao Q, Chen Z, Shoff L, Donly KJ, Gluhak-Heinrich J, Chun YH, Harris SE, MacDougall, M, Chen S. Bmp2 deletion causes an amelogenesis imperfecta phenotype via regulating enamel gene expression J Cell Physiol 2015 Jan;230:1871-1882. |
| Guo F, Feng J, Wang F, Li W, Gao Q, Chen Z, Shoff L, Donly KJ, Gluhak-Heinrich J, Chun YH, Harris SE, MacDougall, M, Chen S. Bmp2 deletion causes an amelogenesis imperfecta phenotype via regulating enamel gene expression J Cell Physiol 2015 Jan;230:1871-1882. |
| Stout BM, Alent BJ, Pedalino P, Holbrook R, Gluhak-Heinrich J, Cui Y, Harris MA, Gemperli AC, Cochran DL, Deas DE, Harris SE. Enamel matrix derivative: protein components and osteoinductive properties J Periodontol 2014 Feb;85(2):9-17. |
| Stout BM, Alent BJ, Pedalino P, Holbrook R, Gluhak-Heinrich J, Cui Y, Harris MA, Gemperli AC, Cochran DL, Deas DE, Harris SE. Enamel matrix derivative: protein components and osteoinductive properties J Periodontol 2014 Feb;85(2):9-17. |
| Paic F, Igwe JC, Nori R, Kronenberg MS, Franceschetti T, Harrington P, Kuo L, Shin DG, Rowe DW, Harris SE, Kalajzic I. Identification of differentially expressed genes between osteoblasts and osteocytes Bone 2009 Oct;45(4):682-692. |
| Paic F, Igwe JC, Nori R, Kronenberg MS, Franceschetti T, Harrington P, Kuo L, Shin DG, Rowe DW, Harris SE, Kalajzic I. Identification of differentially expressed genes between osteoblasts and osteocytes Bone 2009 Oct;45(4):682-692. |
Review Article |
| Harris SE, Rediske M, Neitzke R, Rakian A. Periodontal Biology: Stem Cells, Bmp2 Gene, Transcriptional Enhancers, and Use of Sclerostin Antibody and Pth for Treatment of Periodontal Disease and Bone Loss Cell Stem cells and Regen Med 2017 Jan;3(1). |
| Harris SE, Rediske M, Neitzke R, Rakian A. Periodontal Biology: Stem Cells, Bmp2 Gene, Transcriptional Enhancers, and Use of Sclerostin Antibody and Pth for Treatment of Periodontal Disease and Bone Loss Cell Stem cells and Regen Med 2017 Jan;3(1). |
Teaching
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| Date | Description | Institution | # Students |
| 10/2018 - Present | Hematopoietic/Lymphoid and Musculoskeletal Systems; Orofacial Pain | The University of Texas Health Science Center | |
| I give 1 lecture a year in this course on bone and teeth biology with emphasis on mechanism of action of various genes in craniofacial biology. | |||
| 10/2018 - Present | Hematopoietic/Lymphoid and Musculoskeletal Systems; Orofacial Pain | The University of Texas Health Science Center | |
| I give 1 lecture a year in this course on bone and teeth biology with emphasis on mechanism of action of various genes in craniofacial biology. | |||
| 1/2007 - Present | Bone & Connective Tissue Biology | The University of Texas Health Science Center | 12 students |
| Course Director | |||
| 1/2007 - Present | Bone & Connective Tissue Biology | The University of Texas Health Science Center | 12 students |
| Course Director | |||
Grants
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Federal |
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| Funding Agency | NIH -NIDCR |
| Title | Trigeminal Afferents Regulation of Apical Periodontitis Development |
| Status | Active |
| Period | 8/2018 - 7/2023 |
| Role | Co-Investigator |
| Grant Detail | Determine the role of sensory nerve input to regulation of cells that drive root development, using osteoblast, scap, and osteoclast cell models, and mouse models with selective removal of various classes of sensory nerves that emanated from the trigeminal ganglion. My role is to help with co-culture of osteoclast, osteoblast, and stem cells of the apical papilla with various sensory nerve cells from the TG, and analysis of the transcriptome changes that are a result of these cells with the TG sensory nerves using a variety of bioinformatic tools. |
| Funding Agency | NIH -NIDCR |
| Title | Trigeminal Afferents Regulation of Apical Periodontitis Development |
| Status | Active |
| Period | 8/2018 - 7/2023 |
| Role | Co-Investigator |
| Grant Detail | Determine the role of sensory nerve input to regulation of cells that drive root development, using osteoblast, scap, and osteoclast cell models, and mouse models with selective removal of various classes of sensory nerves that emanated from the trigeminal ganglion. My role is to help with co-culture of osteoclast, osteoblast, and stem cells of the apical papilla with various sensory nerve cells from the TG, and analysis of the transcriptome changes that are a result of these cells with the TG sensory nerves using a variety of bioinformatic tools. |
| Funding Agency | NIH |
| Title | Enamel with overexpressed ameloblastin |
| Status | Active |
| Period | 4/2017 - 3/2022 |
| Role | Co-Investigator |
| Grant Detail | |
| Funding Agency | NIH |
| Title | Enamel with overexpressed ameloblastin |
| Status | Active |
| Period | 4/2017 - 3/2022 |
| Role | Co-Investigator |
| Grant Detail | |
| Funding Agency | NIH -NIDCR |
| Title | Biphasic Roles of Osx-Wnt-B-catenin Signaling Pathways in Tooth Root Formation |
| Status | Active |
| Period | 7/2015 - 6/2020 |
| Role | Co-Investigator |
| Grant Detail | Subcontract Define mechanism by which postnatal root formation via the Oxs-Wnt-b-catenin pathway. My role is to carry out mechanistic studies using RNA-seq and NGS analysis in WT and mutant root teeth tissue. |
| Funding Agency | NIH -NIDCR |
| Title | Biphasic Roles of Osx-Wnt-B-catenin Signaling Pathways in Tooth Root Formation |
| Status | Active |
| Period | 7/2015 - 6/2020 |
| Role | Co-Investigator |
| Grant Detail | Subcontract Define mechanism by which postnatal root formation via the Oxs-Wnt-b-catenin pathway. My role is to carry out mechanistic studies using RNA-seq and NGS analysis in WT and mutant root teeth tissue. |
| Funding Agency | NIH -NIDCR |
| Title | Bmp2 and Sost Genes and Their Interactions in Stem Cells of the Periodontium |
| Status | Active |
| Period | 6/2015 - 3/2020 |
| Role | Principal Investigator |
| Grant Detail | This grant is to carry out lineage tracing studies of stem cells of the periodontium to alveolar bone osteoblast, cementoblast-cytes, and periodontal ligament cells in vivo in presence and absence of Bmp2 gene, role of Sost gene in Bmp2 action, and genomic and epigenomic network analysis of Bmp2 action in periodontal stem cells. |
| Funding Agency | NIH -NIDCR |
| Title | Bmp2 and Sost Genes and Their Interactions in Stem Cells of the Periodontium |
| Status | Active |
| Period | 6/2015 - 3/2020 |
| Role | Principal Investigator |
| Grant Detail | This grant is to carry out lineage tracing studies of stem cells of the periodontium to alveolar bone osteoblast, cementoblast-cytes, and periodontal ligament cells in vivo in presence and absence of Bmp2 gene, role of Sost gene in Bmp2 action, and genomic and epigenomic network analysis of Bmp2 action in periodontal stem cells. |
| Funding Agency | NIH |
| Title | Ameloblastin concentration on enamel formation |
| Status | Active |
| Period | 9/2016 - 8/2018 |
| Role | Co-Investigator |
| Grant Detail | |
| Funding Agency | NIH |
| Title | Ameloblastin concentration on enamel formation |
| Status | Active |
| Period | 9/2016 - 8/2018 |
| Role | Co-Investigator |
| Grant Detail | |
| Funding Agency | NIH/NIDCR |
| Title | Role of ameloblastin for ameloblasts and enamel formation |
| Status | Active |
| Period | 8/2012 - 7/2017 |
| Role | Consultant |
| Grant Detail | The enamel matrix secreted by ameloblasts provides an environment that requires tight regulation by ameloblasts for mineralization to occur. This proposal seeks to elucidate the role of ameloblastin`s structure for the enamel matrix, ameloblast differentiation and subsequent enamel formation. The importance of ameloblastin concentration, cleavage and internalization are explored to better understand the function of non-amelogenin enamel proteins. Ultimately, results from this research will yield novel therapeutic approaches for oral health care. |
| Funding Agency | NIH/NIDCR |
| Title | Role of ameloblastin for ameloblasts and enamel formation |
| Status | Active |
| Period | 8/2012 - 7/2017 |
| Role | Consultant |
| Grant Detail | The enamel matrix secreted by ameloblasts provides an environment that requires tight regulation by ameloblasts for mineralization to occur. This proposal seeks to elucidate the role of ameloblastin`s structure for the enamel matrix, ameloblast differentiation and subsequent enamel formation. The importance of ameloblastin concentration, cleavage and internalization are explored to better understand the function of non-amelogenin enamel proteins. Ultimately, results from this research will yield novel therapeutic approaches for oral health care. |