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Faculty Detail    
Name BRADLEY K YODER
Director Cell, Molecular, and Developmental Biology Graduate Theme
Director T32 Training Program in Cell and Molecular Biology
Director, P30 Hepatorenal Fibrocystic Disease Core Center
 
Campus Address MCLM 688 Zip 0006
Phone  205-934-0994
E-mail  byoder@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor
Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor
Center  Pathology   Cell Adhesion & Matrix Research Center Professor
Center  Center for Metabolic Bone Disease  Center for Metabolic Bone Disease Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Comprehensive Ctr for Healthy Aging  Comprehensive Ctr for Healthy Aging Professor
Center  Medicine  Comprehensive Diabetes Ctr (Org Ret) Professor
Center  Cystic Fibrosis Research Center  Cystic Fibrosis Research Center Professor
Center  General Clinical Research Center  Nephrology Research & Training Center Professor
Center  Nutrition Sciences   Nutrition Obesity Res Ctr (NORC) Professor
Center  Vision Sciences  Vision Science Research Center Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Genetics, Genomics and Bioinformatics 
Hughes Med-Grad Fellowship Program 
Integrative Genetics Graduate Program 
Medical Scientist Training Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Dr. Bradley K. Yoder (b. 1966), 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. His postdoctoral studies were performed 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 utilized 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 important developmental pathways and how loss of the cilium causes abnormalities in left-right body axis specification, limb and tooth patterning, skin and hair follicle morphogenesis, and impairs endochondrial bone formation. His group is also providing important 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.

Society Memberships
Organization Name Position Held Org Link
American Society of Cell Biology    http://www.ascb.org/ 
American Society of Nephrology    http://www.asn-online.org/ 
National Kidney Foundation    http://www.kidney.org/ 
Society for Developmental Biology    http://www.sdbonline.org/ 

Research/Clinical Interest
Title
Cilia Signaling and Dysfunction in Development and Disease
Description
Cilia come in both motile and immotile forms. While motile cilia were known to have important roles in the lung and respiratory system, primary cilia were largely considered vestigial structures. A major 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 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 enter or are retained in the cilium. We have provided seminal 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 formation 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 cause morbid 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 determined 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 important and innovative insights into how cilia are constructed and how they are established 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.

Selected Publications 
Publication PUBMEDID
Iri D. Louro, Evans E. Bailey, Lindsey S. South, Peggy R. McKie-Bell, Bradley K. Yoder, Conway C. Huang, Ronald L. Johnson, and J. Michael Ruppert. Analysis of GLI function in an epithelial model of malignant transformation. Oncogene In press (2002)   
Bradley K. Yoder*, Noel S. Murcia*, William G. Richards*, Michael L. Mucenski, John R. Dunlap and Richard P. Woychik. The Oak Ridge Polycystic Kidney (orpk) disease gene is required for left-right axis determination. * These authors contributed equally to this manuscript. Development 127: 2347-2355 (2000).   
William G. Richards, William E. Sweeney, Bradley K. Yoder, J. Erby Wilkinson, Richard P. Woychik, and Ellis D. Avner. Epidermal growth factor receptor activity mediates renal cyst formation in polycystic kidney disease. Journal of Clinical Investigation 101: 935-939 (1998)   
BK Yoder. Role of primary cilia in the pathogenesis of polycystic kidney disease.
J Am Soc Nephrol. May;18(5):1381-8. [Epub ahead of print ] (2007).  
 
B Song, CJ Haycraft, HS Seo, BK Yoder, and R Serra. Development of the post-natal growth plate requires intraflagellar transport proteins. Dev Biol. May 1;305(1):202-16. [Epub ahead of print] (2007).   
G Ou, M Koga, OE Blacque, T Murayama, Y Ohshima, JC Schafer, C Li, BK Yoder, MR Leroux, and JM Scholey. Sensory Ciliogenesis in Caenorhabditis elegans: Assignment of IFT components into Distinct Modules Based on Transport and Phenotypic Profiles. Mol Biol Cell. Feb 21; [Epub ahead of print] (2007).   
Courtney J. Haycraft, Qihong Zhang, Buer Song, Walker S. Jackson, Peter J. Detloff, Rosa Serra, and Bradley K. Yoder. Intraflagellar Transport is Essential for Endochondral Bone Formation. Development, 134(2):307-16 (2007).   
SR McGlashan, CJ Haycraft, CG Jensen, BK Yoder, and CA Poole. Articular cartilage and growth plate defects are associated with chondrocyte cytoskeletal abnormalities in Tg737(orpk) mice lacking the primary cilia protein polaris. Matrix Biol. Dec 29; [Epub ahead of print] (2006)   
B Banizs, P Komlosi, MO Bevensee, EM Schwiebert, PD Bell, BK Yoder. Altered intracellular pH regulation and Na+/HCO3- transporter activity in choroid plexus of the cilia defective Tg737orpk mutant mouse. Am J Physiol Cell Physiol. 2006 Dec 20; [Epub ahead of print] (2006)   
JC Schafer, ME. Winkelbauer, CL. Williams, CJ. Haycraft, RA. Desmond, BK. Yoder. IFTA-2 is a conserved cilia protein involved in pathways regulating longevity and dauer formation in C. elegans Journal of Cell Science 119(19):4088 -4100 (2006).   
E Efimenko, OE Blacque, G Ou, CJ Haycraft, BK. Yoder, JM. Scholey , MR. Leroux and P Swoboda C. elegans DYF-2, an ortholog of human WDR19, is a component of the IFT machinery in sensory cilia Molecular Biology of the Cell 17(11):4801-4811 (2006).   
EJ. Michaud1 and BK. Yoder. The Primary Cilium in Cell Signaling and Cancer. Cancer Research 66:6463-6467 (2006)   
BK Yoder. More than just the postal service: novel roles for IFT proteins in signal transduction. Dev Cell. May;10 (5):541-542 (2006).   
BK. Yoder, S. Mulroy, H. Eustace, C Boucher and, R Sandford. Molecular pathogenesis of autosomal dominant polycystic kidney disease. Expert Reviews in Molecular Medicine 8:1-22 (2006)   
BK Yoder. Role of primary cilia in the pathogenesis of polycystic kidney disease.
J Am Soc Nephrol. May;18(5):1381-8. [Epub ahead of print ] (2007)
 
 
Nicolas F. Berbari, Nicholas W. Kin, Neeraj Sharma, Edward J. Michaud, Robert A. Kesterson, and Bradley K. Yoder. Mutations in Traf3ip1 reveal defects in ciliogenesis, embryonic development, and altered cell size regulation. Developmental Biology (in press 2011).    
JR Davenport, AJ Watts, VC Roper, MJ Croyle, TV Groen, JM Wyss, TR. Nagy, RA Kesterson3, and BK Yoder. Conditional disruption of intraflagellar transport in adult mice leads to hyperphagia-induced obesity and slow onset cystic kidney disease. Current Biology Sep 18;17(18):1586-94. Epub 2007  2084209 
Ohazama A, Haycraft CJ, Seppala M, Blackburn J, Ghafoor S, Cobourne M, Martinelli DC, Fan CM, Peterkova R, Lesot H, Yoder BK, Sharpe PT. Primary cilia regulate Shh activity in the control of molar tooth number. Development. 2009 Mar;136(6):897-903. Epub 2009 Feb 11.  2727556 
Edward J Michaud and Bradley K Yoder. Soluble levels of cytosolic tubulin coordinate ciliary length control. Molecular Biol. of the Cell. 22(6):806-16, (2011).   3057705 
Corey L. Williams, Chunmei Li, Katarzyna Kida, Peter N. Inglis, Swetha Mohan, Lucie Semenec, Nathan J. Bialas, Rachel Stupay, Nansheng Chen, Oliver E. Blacque*, Bradley K. Yoder*, and Michel R. Leroux*. MKS and NPHP functional modules establish basal body/transition zone-membrane associations and ciliary gate function during ciliogenesis. *Co-corresponding authors. Journal of Cell Biol. 192(6):1023-41. (2011)  3063147 
Mandy J. Croyle, Jonathan M. Lehman, Amber K. O’Connor, Sunny Y Wong, Erik B. Malarkey, Daniela Iribarne, William E. Dowdle, Trenton R. Schoeb, Zoe M. Verney, Mohammad Athar Edward J. Michaud, Jeremy F. Reiter, and Bradley K. Yoder. Role of Epidermal Primary Cilia in the Homeostasis of Skin and Hair Follicles. Development. 138(9):1675-85 (2011).  3074444 
P. Darwin Bell, Wayne Fitzgibbon, Antine Stenbit, Sandra Gilley, Amber Houston, Kelli Sas, May Amria, Gene P. Siegal, John Bissler, Mehmet Bilgen, Peter Cheng-te Chou, Lisa Guay-Woodford, Bradley K. Yoder, Courtney J. Haycraft Ryan Reichert, and Brian Siroky. Interactions between Cilia, Hypertrophic Signaling, and Renal Cystogensis. Journal of American Society for Neprhology, (2011). PMCID: PMC3083306  3083306 
Anastasia D. Egorova, Padmini P.S.J. Khedoe, Marie-Jose T.H. Goumans, Bradley K Yoder, Surya M. Nauli, Peter ten Dijke, Robert E. Poelmann, and Beerend P. Hierck. Lack of primary cilia primes shear-induced Endothelial-to-Mesenchymal Transition. Circulation Research, 108(9):1093-101 (2011).  3094764 
Svetlana V. Masyukova, Marlene E. Winkelbauer, Corey L. Williams, Jay N. Pieczynski, and Bradley K. Yoder Assessing the pathogenic potential of human Nephronophthisis disease-associated NPHP-4 missense mutations in C. elegans. Human Molecular Genetics 20:2942-2954. (2011)   3131040 
Patrick D. Taulman, Courtney J. Haycraft, Daniel F. Balkovetz, and Bradley K Yoder. Polaris, a protein involved in left-right axis patterning, localizes to basal bodies and cilia. Molecular Biology of the Cell 12:589-599 (2001)  11251073 
Courtney J. Haycraft, Peter Swoboda, Patrick D. Taulman, James H. Thomas, Bradley K. Yoder. The C. elegans homologue of the murine cystic kidney disease gene Tg737 functions in a ciliogenic pathway and is disrupted in osm-5 mutant worms. Development 128:1493-1505 (2001)  11290289 
Bradley K. Yoder, Albert Tousson, Leigh Millican, John H. Wu, Charles E. Bugg, Jr., James A. Schafer, and Daniel F. Balkovetz. Polaris, a protein disrupted in Oak Ridge Polycystic Kidney mutant mice is required for assembly of renal cilium. American Journal of Physiol. Renal 282: F541-F552 (2002).  11832437 
Xiaoying Hou, Michal Mrug, Bradley K. Yoder, Elliot J. Lefkowitz, Gabriel Kremmidiotis, Peter DEustachio, David R. Beier, and Lisa M. Guay-Woodford. 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).  11854326 
Bradley K. Yoder and Susan M. Sell. Jets: a modification to speed flexible oligonucleotide array construction. The Pharmacogenomics Journal 1:163-165 (2001)  11908749 
Jin Billy Li, Jantje M. Gerdes, Courtney J. Haycraft, Yanli Fan, Tanya M. Teslovich, Helen May-Simera, Haitao Li, , Oliver Blacque, Linya Li, Carmen C. Leitch, Richard Allan Lewis, Jane S. Green, Patrick S. Parfrey, Michel R. Leroux, William S. Davidson, Philip L. Beales, Lisa M. Guay-Woodford, Bradley K. Yoder, Gary D. Stormo, Nicholas Katsanis, and Susan K. Dutcher. Comparative genomic identification of conserved flagellar and basal body proteins that includes a novel gene for Bardet- Biedl syndrome. Cell 117(4):541-52 (2004)  15137946  
Qihong Zhang, James. R Davenport., Mandy J. Croyle, C.J. Haycraft, and B.K Yoder. Disruption of IFT results in both exocrine and endocrine abnormalities in the pancreas of Tg737orpk mutant mice. Laboratory Investigation 85:45-64 (2005).  15580285  
AG Kramer-Zucker, F Olale, CJ Haycraft, BK. Yoder, AF Schier, and IA Drummond. Cilia-driving fluid flow is the zebrafish pronephros, brain and Kupffers vesicle is required for normal organogenesis. Development 132: 1907-1921(2005)  15790966  
Liu W, Murcia NS, Duan Y, Weinbaum S, Yoder BK, Schwiebert E, Satlin LM. Mechanoregulation of intracellular Ca2+ concentration is attenuated in collecting duct of monocilium-impaired orpk mice. Am J Physiol Renal Physiol. 289(5):F978-88. (2005)  15972389  
Olteanu D, Yoder BK, Liu W, Croyle MJ, Welty EA, Rosborough K, Wyss JM, Bell PD, Guay-Woodford LM, Bevensee MO, Satlin LM, Schwiebert EM. Heightened ENaC-mediated Sodium Absorption in a Murine Polycystic Kidney Disease Model Epithelium Lacking Apical Monocilia. American Journal of Physiology 290: C952-63 (2005).  16207792  
Courtney J. Haycraft, Boglarka Banizs, Yesim Aydin-Son, Edward J. Michaud, Bradley K. Yoder. Gli2 and Gli3 localize to cilia and require intraflagellar transport for function. PLOS Genetics PLoS Genet 2005 Oct;1(4):e53. Epub 2005 Oct 28. (2005.  16254602  
James R. Davenport and Bradley K. Yoder An incredible decade for the cilium: A look at a once forgotten organelle. American Journal of Physiology 289(6):F1159-69 (2005).  16275743  
Banizs B, Pike MM, Millican CL, Ferguson WB, Komlosi P, Sheetz J, Bell PD, Schwiebert EM, Yoder BK. Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. Development 132(23):5329-39. (2005)  16284123  
Marlene E. Winkelbauer, Jenny C. Schafer, Courtney J. Haycraft, Peter Swoboda, and Bradley K. Yoder. The C. elegans homologs of Nephrocystin-1 and Nephrocystin-4 are cilia transition zone proteins involved in chemosensory perception. Journal of Cell Science 118(Pt 23):5575-87 (2005)  16291722  
Siroky BJ, Ferguson WB, Fuson AL, Xie Y, Fintha A, Komlosi P, Yoder BK, Schwiebert EM, Guay-Woodford LM, Bell PD. Loss of Primary Cilia Results in Deregulated and Unabated Apical Calcium Entry in ARPKD Collecting Duct Cells. Am J Physiol Renal Physiol. 290:F1320-8 (2006)  16396941  
Courtney J. Haycraft, Qihong Zhang, Buer Song, Walker S. Jackson, Peter J. Detloff, Rosa Serra, and Bradley K. Yoder. Intraflagellar Transport is Essential for Endochondral Bone Formation. Development, 134(2):307-16 (2007).   17166921  
B Banizs, P Komlosi, MO Bevensee, EM Schwiebert, PD Bell, BK Yoder. Altered intracellular pH regulation and Na+/HCO3- transporter activity in choroid plexus of the cilia defective Tg737orpk mutant mouse. Am J Physiol Cell Physiol. 2006 Dec 20; [Epub ahead of print] (2006)  17182727 
SR McGlashan, CJ Haycraft, CG Jensen, BK Yoder, and CA Poole. Articular cartilage and growth plate defects are associated with chondrocyte cytoskeletal abnormalities in Tg737(orpk) mice lacking the primary cilia protein polaris. Matrix Biology, 26(4):234-46 (2006).  17289363  
G Ou, M Koga, OE Blacque, T Murayama, Y Ohshima, JC Schafer, C Li, BK Yoder, MR Leroux, and JM Scholey. Sensory Ciliogenesis in Caenorhabditis elegans: Assignment of IFT components into Distinct Modules Based on Transport and Phenotypic Profiles. Mol Biol Cell. Feb 21; [Epub ahead of print] (2007).  17314406 
B Song, CJ Haycraft, HS Seo, BK Yoder, and R Serra. Development of the post-natal growth plate requires intraflagellar transport proteins. Dev Biol. May 1;305(1):202-16. [Epub ahead of print] (2007).  17359961  
VV Chizhikov,, JR Davenport, Q Zhang, EK Shih, OA Cabello, J Fuchs, BK Yoder and KJ Millen. Cilia proteins control cerebellar morphogenesis by promoting granule progenitor pool expansion. Journal of Neuroscience Sep 5;27(36):9780-9.(2007)  17804638  
JR Davenport, AJ Watts, VC Roper, MJ Croyle, TV Groen, JM Wyss, TR. Nagy, RA Kesterson3, and BK Yoder. Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease. Current Biology Sep 18;17(18):1586-94. Epub 2007 Sep 6. (2007)  17825558  
C Jones, VC Roper, I Foucher, D Qian, B Banizs, C Petit, BK Yoder, and P Chen. Ciliary proteins link basal body polarization to planar cell polarity regulation. Nat Genet. 40(1):69-77. Epub 2007 Dec 9. (2008)  18066062  
PV Tran, CJ Haycraft, TY Besschetnova, A Turbe-Doan, RW Stottmann, BJ Herron, AL Chesebro, H Qiu, PJ Scherz, JV Shah, BK Yoder, and DR Beier. THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet. 2008  18327258  
CL Williams, ME Winkelbauer, JC Schafer, EJ Michaud, and BK Yoder. Functional Redundancy of the B9 Proteins and Nephrocystins in C. elegans Ciliogenesis. Mol Biol Cell. 2008  18337471  
JM Lehman, EJ Michaud, TR Schoeb, Y Aydin-Son, M Miller, BK Yoder. The Oak Ridge Polycystic Kidney mouse: Modeling ciliopathies of mice and men. Developmental Dynamics 237(8):1960-71. 2008  18366137  

Keywords
Cilia, cystic kidney diseases, obesity, signal transduction, cell fate determination and embryonic patterning, birth defects, mouse and C. elegans models.