Bradley Yoder Ph.D.

Bradley Yoder Ph.D.
Professor / Chairperson

Senior Scientist, Cancer Cell Biology , O'Neal Comprehensive Cancer Center

Overview

Dr. Bradley K. Yoder, Professor, completed his undergraduate studies in biochemistry and molecular biology at the University of Maryland Baltimore County (B.S. 1988) and received a Ph.D. in molecular and cellular biology from the University of Maryland in 1993. He completed his postdoctoral studies at Oak Ridge National Laboratory under the guidance of Dr. Rick Woychik, where Dr. Yoder was an Alexander Hollaender Distinguished Postdoctoral Fellow. His research over the past two decades has focused on the cellular and molecular mechanisms regulating assembly, maintenance, and function of the primary cilium utilizing complementary approaches in mice, C. elegans, and in cell culture models. Work from his laboratory has used genetic screens in C. elegans to identify proteins required for ciliogenesis and cilia mediated signaling activities and how these genes function in pathways (e.g., Daf-2 Insulin/IGF-like pathway) that regulate life span and energy homeostasis. His group has analyzed in mammalian systems how the cilium regulates critical developmental pathways and how the loss of the cilium causes abnormalities in left-right body axis specification, limb and tooth patterning, skin, and hair follicle morphogenesis, and impairs endochondral bone formation. His group is also providing critical fundamental insights into the connection between ciliary dysfunction and cystic kidney disorders, and novel roles for neuronal cilia in the regulation of satiation responses, disruption of which causes obesity and type II diabetes.

Selected Publications

Academic Article

Year	Title	Altmetric
2021	Early infiltrating macrophage subtype correlates with late-stage phenotypic outcome in a mouse model of hepatorenal fibrocystic disease. Laboratory Investigation. 101:1382-1393. 2021
2021	A ciliopathy complex builds distal appendages to initiate ciliogenesis 2021
2021	Kidney resident macrophages in the rat have minimal turnover and replacement by blood monocytes 2021
2021	Ly6chi Infiltrating Macrophages Promote Cyst Progression in Injured Conditional Ift88 Mice. 2021
2021	A mouse model of BBS identifies developmental and homeostatic effects of BBS5 mutation and identifies novel pituitary abnormalities. Human Molecular Genetics. 30:234-246. 2021
2021	Resident Macrophages in Cystic Kidney Disease. 2021
2021	A transgenic Alx4-CreER mouse to analyze anterior limb and nephric duct development. Developmental Dynamics. 2021
2020	Human transcription factors responsive to initial reprogramming predominantly undergo legitimate reprogramming during fibroblast conversion to iPSCs. Scientific Reports. 10. 2020
2020	BBSome component BBS5 is required for cone photoreceptor protein trafficking and outer segment maintenance. Investigative Ophthalmology and Visual Science. 61. 2020
2020	Interferon Regulatory Factor-5 in Resident Macrophage Promotes Polycystic Kidney Disease. 2020
2019	Increased flux through the mevalonate pathway mediates fibrotic repair without injury. Journal of Clinical Investigation. 129:4962-4978. 2019
2019	Single-cell RNA sequencing identifies candidate renal resident macrophage gene expression signatures across species. Journal of the American Society of Nephrology. 30:767-781. 2019
2019	Heterozygous Pkhd1^C642* mice develop cystic liver disease and proximal tubule ectasia that mimics radiographic signs of medullary sponge kidney 2019
2019	Truncating PKHD1 and PKD2 mutations alter energy metabolism 2019
2019	Resident macrophages reprogram toward a developmental state after acute kidney injury. JCI insight. 4. 2019
2019	Mks6 mutations reveal tissue-and cell type-specific roles for the cilia transition zone. The FASEB Journal. 33:1440-1455. 2019
2019	Tissue-resident macrophages promote renal cystic disease. Journal of the American Society of Nephrology. 30:1841-1856. 2019
2019	Urinary T cells correlate with rate of renal function loss in autosomal dominant polycystic kidney disease. Physiological Reports. 7. 2019
2018	Role for intraflagellar transport in building a functional transition zone. EMBO Reports. 19. 2018
2018	Primary cilia disruption differentially affects the infiltrating and resident macrophage compartment in the liver 2018
2018	Ectopic Phosphorylated Creb Marks Dedifferentiated Proximal Tubules in Cystic Kidney Disease. American Journal of Pathology. 188:84-94. 2018
2016	Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease. PLoS Genetics. 12. 2016
2016	The tumor-associated glycosyltransferase ST6Gal-I regulates stem cell transcription factors and confers a cancer stem cell phenotype. Cancer Research. 76:3978-3988. 2016
2016	Coiled-coil domain containing 42 (Ccdc42) is necessary for proper sperm development and male fertility in the mouse. Developmental Biology. 412:208-218. 2016
2016	A Screen for Modifiers of Cilia Phenotypes Reveals Novel MKS Alleles and Uncovers a Specific Genetic Interaction between osm-3 and nphp-4. PLoS Genetics. 12. 2016
2016	Non-essential role for cilia in coordinating precise alignment of lens fibres. Mechanisms of Development. 139:10-17. 2016
2015	KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome. Genome Biology. 16. 2015
2015	Genetic and informatic analyses implicate Kif12 as a candidate gene within the Mpkd2 locus that modulates renal cystic disease severity in the Cys1^cpk mouse. PLoS ONE. 10. 2015
2015	Heterotrimeric Kinesin-2 (KIF3) mediates transition zone and axoneme formation of mouse photoreceptors. Journal of Biological Chemistry. 290:12765-12778. 2015
2015	Snap Shot: Sensing and signaling by cilia. Cell. 161:692-692.e1. 2015
2014	High-throughput genome editing and phenotyping facilitated by high resolution melting curve analysis. PLoS ONE. 9. 2014
2014	Complement C3 activation in cyst fluid and urine from autosomal dominant polycystic kidney disease patients. Journal of Internal Medicine. 276:539-540. 2014
2014	Hippocampal and cortical primary cilia are required for aversive memory in mice. PLoS ONE. 9. 2014
2014	Primary cilia enhance kisspeptin receptor signaling on gonadotropin- releasing hormone neurons 2014
2014	Aberrant expression of laminin-332 promotes cell proliferation and cyst growth in ARPKD 2014
2014	Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways 2014
2014	Monitoring endosomal trafficking of the g protein-coupled receptor somatostatin receptor 3. Methods in Enzymology. 534:261-280. 2014
2013	An inducible CiliaGFP mouse model for in vivo visualization and analysis of cilia in live tissue. Cilia. 2. 2013
2013	Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice 2013
2013	Quantitative Peptidomics of Purkinje Cell Degeneration Mice. PLoS ONE. 8. 2013
2013	Proximal tubule proliferation is insufficient to induce rapid cyst formation after cilia disruption. Journal of the American Society of Nephrology. 24:456-464. 2013
2013	Microtubule modifications and stability are altered by cilia perturbation and in cystic kidney disease. Cytoskeleton. 70:24-31. 2013
2012	Mammalian Clusterin associated protein 1 is an evolutionarily conserved protein required for ciliogenesis. Cilia. 1. 2012
2012	Gene therapy rescues cilia defects and restores olfactory function in a mammalian ciliopathy model. Nature Medicine. 18:1423-1428. 2012
2012	Kidney injury accelerates cystogenesis via pathways modulated by heme oxygenase and complement. Journal of the American Society of Nephrology. 23:1161-1171. 2012
2012	Increased Na⁺/H⁺ exchanger activity on the apical surface of a cilium-deficient cortical collecting duct principal cell model of polycystic kidney disease 2012
2011	Assessing the pathogenic potential of human nephronophthisis disease-associated NPHP-4 missense mutations in C. elegans. Human Molecular Genetics. 20:2942-2954. 2011
2011	Loss of primary cilia upregulates renal hypertrophic signaling and promotes cystogenesis. Journal of the American Society of Nephrology. 22:839-848. 2011
2011	Role of epidermal primary cilia in the homeostasis of skin and hair follicles 2011
2011	Lack of primary cilia primes shear-induced endothelial-to-mesenchymal transition. Circulation Research. 108:1093-1101. 2011
2011	MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis 2011
2011	Soluble levels of cytosolic tubulin regulate ciliary length control 2011
2011	GMAP210 and IFT88 are present in the spermatid golgi apparatus and participate in the development of the acrosome-acroplaxome complex, head-tail coupling apparatus and tail. Developmental Dynamics. 240:723-736. 2011
2011	Erratum: In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells (Cell Stem Cell (2010) 7 (744-758)). Cell Stem Cell. 8:119. 2011
2011	Mutations in Traf3ip1 reveal defects in ciliogenesis, embryonic development, and altered cell size regulation. Developmental Biology. 360:66-76. 2011
2010	In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells. Cell Stem Cell. 7:744-758. 2010
2010	The zebrafish foxj1a transcription factor regulates cilia function in response to injury and epithelial stretch 2010
2010	Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts. Cellular Physiology and Biochemistry. 25:279-292. 2010
2010	Normal ciliogenesis requires synergy between the cystic kidney disease genes MKS-3 and NPHP-4. Journal of the American Society of Nephrology. 21:782-793. 2010
2009	The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation. Journal of Cell Science. 122:3070-3082. 2009
2009	The Primary Cilium as a Complex Signaling Center. Current Biology. 19. 2009
2009	Primary cilia regulate Shh activity in the control of molar tooth number 2009
2009	Primary cilia and signaling pathways in mammalian development, health and disease 2009
2009	An essential role for dermal primary cilia in hair follicle morphogenesis. Journal of Investigative Dermatology. 129:438-448. 2009
2009	Generating conditional mutants to analyze ciliary functions: the use of Cre-lox technology to disrupt cilia in specific organs.. Methods in Cell Biology. 93:305-330. 2009
2009	Utilization of conditional alleles to study the role of the primary cilium in obesity.. Methods in Cell Biology. 94:162-179. 2009
2008	Chapter 13 Ciliary Dysfunction in Developmental Abnormalities and Diseases. Current Topics in Developmental Biology. 85:371-427. 2008
2008	Preface. Current Topics in Developmental Biology. 85. 2008
2008	Characterization of primary cilia and hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines. Developmental Dynamics. 237:2039-2052. 2008
2008	Role for primary cilia in the regulation of mouse ovarian function. Developmental Dynamics. 237:2053-2060. 2008
2008	The Oak Ridge Polycystic Kidney mouse: Modeling ciliopathies of mice and men. Developmental Dynamics. 237:1960-1971. 2008
2008	Loss of apical monocilia on collecting duct principal cells impairs ATP secretion across the apical cell surface and ATP-dependent and flow-induced calcium signals. Purinergic Signalling. 4:155-170. 2008
2008	Functional redundancy of the B9 proteins and nephrocystins in Caenorhabditis elegans ciliogenesis 2008
2008	THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nature Genetics. 40:403-410. 2008
2008	Ciliary proteins link basal body polarization to planar cell polarity regulation. Nature Genetics. 40:69-77. 2008
2007	Disruption of Intraflagellar Transport in Adult Mice Leads to Obesity and Slow-Onset Cystic Kidney Disease. Current Biology. 17:1586-1594. 2007
2007	Cilia proteins control cerebellar morphogenesis by promoting expansion of the granule progenitor pool 2007
2007	Articular cartilage and growth plate defects are associated with chondrocyte cytoskeletal abnormalities in Tg737^orpk mice lacking the primary cilia protein polaris 2007
2007	Development of the post-natal growth plate requires intraflagellar transport proteins. Developmental Biology. 305:202-216. 2007
2007	Role of primary cilia in the pathogenesis of polycystic kidney disease. Journal of the American Society of Nephrology. 18:1381-1388. 2007
2007	Sensory ciliogenesis in Caenorhabditis elegans: Assignment of IFT components into distinct modules based on transport and phenotypic profiles 2007
2007	Altered pHi regulation and Na⁺/HCO^-3 transporter activity in choroid plexus of cilia-defective Tg737^orpk mutant mouse 2007
2007	Intraflagellar transport is essential for endochondral bone formation 2007
2006	Caenorhabditis elegans DYF-2, an orthologue of human WDR19, is a component of the intraflagellar transport machinery in sensory cilia 2006
2006	IFTA-2 is a conserved cilia protein involved in pathways regulating longevity dauer formation in Caenorhabditis elegans. Journal of Cell Science. 119:4088-4100. 2006
2006	The primary cilium in cell signaling and cancer. Cancer Research. 66:6463-6467. 2006
2006	Loss of primary cilia results in deregulated and unabated apical calcium entry in ARPKD collecting duct cells 2006
2006	More Than Just the Postal Service: Novel Roles for IFT Proteins in Signal Transduction. Developmental Cell. 10:541-542. 2006
2006	Heightened epithelial Na⁺ channel-mediated Na⁺ absorption in a murine polycystic kidney disease model epithelium lacking apical monocilia 2006
2006	Molecular pathogenesis of autosomal dominant polycystic kidney disease. Expert Reviews in Molecular Medicine. 8:1-22. 2006
2005	An incredible decade for the primary cilium: A look at a once-forgotten organelle 2005
2005	Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus 2005
2005	The C. elegans homologs of nephrocystin-1 and nephrocystin-4 are cilia transition zone proteins involved in chemosensory perception. Journal of Cell Science. 118:5575-5587. 2005
2005	Mechanoregulation of intracellular Ca²⁺ concentration is attenuated in collecting duct of monocilium-impaired orpk mice 2005
2005	Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function.. PLoS Genetics. 1. 2005
2005	Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis 2005
2005	Disruption of IFT results in both exocrine and endocrine abnormalities in the pancreas of Tg737^orpk mutant mice. Laboratory Investigation. 85:45-64. 2005
2005	Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genetics. 1:0480-0488. 2005
2004	Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell. 117:541-552. 2004
2004	Cystic kidney diseases: All roads lead to the cilium 2004
2003	A novel dynein light intermediate chain colocalizes with the retrograde motor for intraflagellar transport at sites of axoneme assembly in Chlamydomonas and mammalian cells 2003
2003	Loss of the Tg737 protein results in skeletal patterning defects. Developmental Dynamics. 227:78-90. 2003
2003	XBX-1 encodes a dynein light intermediate chain required for retrograde intraflagellar transport and cilia assembly in Caenorhabditis elegans 2003
2003	Identification of CHE-13, a novel intraflagellar transport protein required for cilia formation. Experimental Cell Research. 284:249-261. 2003
2002	Comparative gene expression profile analysis of GLI and c-MYC in an epithelial model of malignant transformation. Cancer Research. 62:5867-5873. 2002
2002	The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. Journal of the American Society of Nephrology. 13:2508-2516. 2002
2002	Polaris, a protein disrupted in orpk mutant mice, is required for assembly of renal cilium. 2002
2002	Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease.. Journal of Clinical Investigation. 109:533-540. 2002
2002	Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease. Journal of Clinical Investigation. 109:533-540. 2002
2002	Polaris, a protein disrupted in orpk mutant mice, is required for assembly of renal cilium 2002
2001	The C. elegans homolog of the murine cystic kidney disease gene Tg737 functions in a ciliogenic pathway and is disrupted in osm-5 mutant worms 2001
2001	Jets: A modification to speed flexible oligonucleotide array construction 2001
2001	Polaris, a protein involved in left-right axis patterning, localizes to basal bodies and cilia 2001
2000	The Oak Ridge Polycystic Kidney (orpk) disease gene is required for left-right axis determination 2000
1998	Epidermal growth factor receptor activity mediates renal cyst formation in polycystic kidney disease. Journal of Clinical Investigation. 101:935-939. 1998
1998	Characterization of growth factor responsiveness and alterations in growth factor homeostasis involved in the tumorigenic conversion of mouse oval cells. Growth Factors. 15:81-94. 1998
1997	The combination of epidermal growth factor and transforming growth factor-β induces novel phenotypic changes in mouse liver stem cell lines. Journal of Cell Science. 110:3117-3129. 1997
1997	Differential rescue of the renal and hepatic disease in an autosomal recessive polycystic kidney disease mouse mutant: A new model to study the liver lesion. American Journal of Pathology. 150:2231-2241. 1997
1997	Isolation and characterization of liver epithelial cell lines from wild- type and mutant TgN737Rpw mice. American Journal of Pathology. 150:1189-1197. 1997
1997	The tetratricopeptide repeat containing Tg737 gene is a liver neoplasia tumor suppressor gene. Oncogene. 15:1797-1803. 1997
1996	Oval cell proliferation associated with the murine insertional mutation TgN737Rpw. American Journal of Pathology. 149:1919-1930. 1996
1996	Functional correction of renal defects in a mouse model for ARPKD through expression of the cloned wild-type Tg737 cDNA. Kidney International. 50:1240-1248. 1996
1995	Insertional mutagenesis and molecular analysis of a new gene associated with polycystic kidney disease.. Proceedings of the Association of American Physicians. 107:314-323. 1995
1994	Identification of a new spore coat protein gene in the cellular slime mold Dictyostelium discoideum. Developmental Biology. 163:49-65. 1994
1994	The promoter of a gene encoding a novel Dictyostelium spore coat protein. Developmental Biology. 163:38-48. 1994
1991	Gene expression and chromatin structure in the cellular slime mold, Dictyostelium discoideum 1991

Chapter

Year	Title	Altmetric
2019	Intravital visualization of the primary cilium, tubule flow, and innate immune cells in the kidney utilizing an abdominal window imaging approach. 67-83. 2019
2018	Cilia and polycystic kidney disease. 87-110. 2018
2017	Inflammation and fibrosis in polycystic kidney disease. 323-344. 2017
2013	Renal Cilia Structure, Function, and Physiology. 319-346. 2013
2013	Neuronal cilia and obesity. 165-191. 2013

Research Overview

Cilia come in both motile and immotile forms. While motile cilia were known to have essential roles in the lung and respiratory system, primary cilia were widely considered vestigial structures. A significant paradigm shift in the field occurred with the generation of mouse mutants (such as the orpk mouse) that disrupt cilia formation. These new mouse mutants revealed important and novel roles for motile and immotile cilia and demonstrated that they are essential for mammalian development and tissue function. Defects in cilia have been implicated as the cause of a large and rapidly expanding group of human syndromes (Ciliopathies) with a wide range of developmental and disease phenotypes.

The objectives of my research program are to uncover mechanisms regulating assembly, maintenance, and functions of both motile and primary forms of cilia and to determine how defects in these processes contribute to developmental abnormalities and disease pathogenesis. To accomplish these goals, my group utilizes complementary cell, genetic, and biochemical approaches in mice, C. elegans, and cell culture to identify new proteins involved in ciliogenesis and cilia mediated signaling. Work from my group has identified novel components of the ciliary transition zone, an important domain controlling what protein enters or is retained in the cilium. We have provided critical insights into how the cilium regulates developmental pathways, such as hedgehog, and how alterations in cilia-mediated regulation of this pathway cause polydactyly, defects in endochondral bone formation, and abnormal skin and hair follicle morphogenesis. My group made fundamental contributions that connected ciliary dysfunction to the creation of cysts in the kidney, liver, and pancreas, and uncovered a new role for cilia on hypothalamic neurons in regulating satiation responses. We have shown that disruption of cilia on these neurons causes obesity and type II diabetes. We also identified genes important in regulating ciliary motility and waveform and determined that their loss in mice leads to hydrocephalus, bronchiectasis, and randomization of the left-right body axis. Importantly, as part of this work, we discovered that a mutation of one of these genes we identified in our mouse model is responsible for a form of primary ciliary dyskinesia (PCD) in humans. As in the mouse model, these human PCD patients frequently have left-right body situs defects.

In summary, the research conducted by my group is providing essential and innovative insights into how cilia are constructed and how they establish themselves as a unique signaling and sensory organelle with a distinct protein composition the rest of the cell membrane. We have uncovered many diverse and unexpected roles for cilia during development and in maintaining mammalian health.