Impact of the Xenopus system on the missions of the NIDDK
Oliver Wessely, PhD. - Louisiana State University Health Science Center
Xenopus has played a very important role in the mission of NIDDK for a long time.� Xenopus oocytes have been and still are an invaluable system to study the conductive properties of many channels and transporters expressed on renal epithelial cells. Many recent technological advances such as antisense morpholino oligomers for gene knockdowns, transgenic GFP lines for imaging and the genome information for X. tropicalis have promoted Xenopus as a valuable model not only to study early embryonic development, but also to investigate organogenesis. This has been realized by NIDDK and projects exploring the pronephric kidney, the pancreas and the liver are among the currently funded grants.
Electrophysiology using Xenopus oocytes: Xenopus oocytes express a low number of endogenous membrane transporters and channels because they are virtually independent from exogenous nutrients. As such they have been and are the preferred in vivo model to characterize channels, receptors and transporters present on renal epithelial cells that are crucially important for kidney function. Oocytes are used to study electrophysiological properties, stoichiometries and the role of post-translational modification. The system is also very amendable to high-throughput screening approaches. As such it has been a powerful tool to perform functional screens for genes encoding ion channels and transporters. In addition to their basic science component these studies have significant impact in respect to human diseases. For example, studies on hypertension have used Xenopus oocytes to demonstrate that defects in With no Lysine kinase 4 (WNK4) causes increased activity of the renal transporter molecules NKCC2 and NCC and thereby directly interferes with blood pressure control.
Kidney Development: Xenopus embryos due to their aquatic life develop a functional pronephric kidney within 31 hours post fertilization. Thus, Xenopus has been established as a valuable animal model to study kidney development. Over the years, it has become evident that the process of kidney development is evolutionary conserved and findings in Xenopus are directly applicable to studies in higher vertebrates such as humans and mouse. One of the most recent advances was the realization that Xenopus is a powerful model organism to study the patterning of the nephron along its proximal-distal axis. With the availability of the Xenopus tropicalis genome it was possible to identify many structural proteins that are specifically expressed in defined segments of the pronephros. This patterning was highly reminiscent to the one found in individual nephrons of the metanephric kidney. It provided a novel angle to understand how transcription factors actually pattern the kidney along its proximal distal axis as illustrated by the recent study on the Iroquois (Irx) gene family. Similarly, the synchronous development of the Xenopus pronephros has also provided many novel insights in how kidney progenitors differentiate into their mature counterparts (e.g. the blood-filtering podocyte) or how microRNAs regulate terminal differentiation of the renal epithelial cells.
In addition to understanding the processes that regulate normal kidney development, the pronephric kidney of Xenopus is also a valuable tool to study kidney diseases. Knockdown of genes mutated in human forms of Polycystic Kidney Disease result in a �PKD-like� phenotype in Xenopus that is used to better understand the molecular mechanisms leading to kidney cyst formation. In particular, the speed of analysis and the nearly unlimited availability of embryos provide an ideal in vivo test system to study aspect of Polycystic Kidney Disease that cannot be performed in mouse as easily.
Finally, the Xenopus kidney is a great system to study tissue engineering. Xenopus was the first organism, where it could be shown that the combined action of Retinoic Acid and Activin can convert primitive ectoderm into a functional kidney that can even be transplanted in nephrectomized Xenopus embryos. Ongoing work has extended these studies to several cell types in the kidney and has played an important role in identifying novel kidney-specific genes as well as ways to generate kidney epithelial cells in vitro.
Pancreas Development: The formation of the pancreas and the control of islet cell differentiation is one of the most coveted models of lineage specification. It is of high clinical importance due to its disturbance during diabetes. While mouse and chick have been the traditional models to study pancreas formation, the Xenopus pancreas has been developed as a viable alternative. Even though there are differences at later stages of pancreas development and its reorganization during metamorphosis, the early pancreas development in Xenopus is very similar to that of mice and humans. Many results are directly applicable to mammalian systems. In fact, one of the most important genes in pancreatic development, Pdx1, was initially discovered in Xenopus. The current research in Xenopus pancreas development follows similar avenues as outlined for the kidney. However, one particular interest is directed towards developing a transcriptional network of pancreas development in an effort to understand how early endodermal progenitors are specified first to a pancreatic fate, then to an endocrine fate and finally to a beta cell fate. For this approach Xenopus is uniquely suited since combinatorial knockdown studies using antisense morpholino oligomers allow analyses that are much more time-effective than compound mouse mutants.
Liver Development: Another organ system that has recently found more attention in Xenopus is the liver. The liver is an essential organ, yet the molecular basis of liver development is still poorly understood. Therefore, liver transplantation is often the only option for life threatening liver malfunctions. In an effort to develop alternative treatment options such as tissue replacement therapies from stem cells, the processes involved in hepatic tissue specification and the initial patterning of the foregut domain that will give rise to the liver are of high interest. Using the advantages of Xenopus it was recently shown that liver development relies on canonical and noncanonical Wnt signaling. Both pathways are necessary, but their activities have to be coordinated correctly to promote proper outgrowth of the liver bud.
Selected References:
Asashima, M., Ito, Y., Chan, T., Michiue, T., Nakanishi, M., Suzuki, K., Hitachi, K., Okabayashi, K., Kondow, A., and Ariizumi, T. (2009). In vitro organogenesis from undifferentiated cells in Xenopus. Dev. Dyn. 238, 1309-1320.
Chan, T.C., Ariizumi, T., and Asashima, M. (1999). A model system for organ engineering: transplantation of in vitro induced embryonic kidney. Naturwissenschaften 86, 224-227.
Gerth, V.E., Zhou, X., and Vize, P.D. (2005). Nephrin expression and three-dimensional morphogenesis of the Xenopus pronephric glomus. Dev. Dyn. 233, 1131-1139.
Hayata, T., Blitz, I.L., Iwata, N., and Cho, K.W. (2009). Identification of embryonic pancreatic genes using Xenopus DNA microarrays. Dev. Dyn. 238, 1455-1466.
Jarikji, Z., Horb, L.D., Shariff, F., Mandato, C.A., Cho, K.W., and Horb, M.E. (2009). The tetraspanin Tm4sf3 is localized to the ventral pancreas and regulates fusion of the dorsal and ventral pancreatic buds. Development 136, 1791-1800.
Li, Y., Rankin, S.A., Sinner, D., Kenny, A.P., Krieg, P.A., and Zorn, A.M. (2008). Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling. Genes Dev. 22, 3050-3063.
Mukhi, S., Horb, M.E., and Brown, D.D. (2009). Remodeling of insulin producing beta-cells during Xenopus laevis metamorphosis. Dev. Biol. 328, 384-391.
Papke, R.L., and Smith-Maxwell, C. (2009). High throughput electrophysiology with Xenopus oocytes. Comb. Chem. High Throughput Screen. 12, 38-50.
Pearl, E.J., Bilogan, C.K., Mukhi, S., Brown, D.D., and Horb, M.E. (2009). Xenopus pancreas development. Dev. Dyn. 238, 1271-1286.
Raciti, D., Reggiani, L., Geffers, L., Jiang, Q., Bacchion, F., Subrizi, A.E., Clements, D., Tindal, C., Davidson, D.R., Kaissling, B., et al. (2008). Organization of the pronephric kidney revealed by large-scale gene expression mapping. Genome Biol. 9, R84.
Reggiani L, Raciti D, Airik R, Kispert A, Br�ndli AW. 2007 The prepattern transcription factor Irx3 directs nephron segment identity. Genes Dev 21: 2358-2370.
Spagnoli, F.M., and Brivanlou, A.H. (2008). The Gata5 target, TGIF2, defines the pancreatic region by modulating BMP signals within the endoderm. Development 135, 451-461.
Taelman, V., Van Campenhout, C., Solter, M., Pieler, T., and Bellefroid, E.J. (2006). The Notch-effector HRT1 gene plays a role in glomerular development and patterning of the Xenopus pronephros anlagen. Development 133, 2961-2971.
Tran, U., Pickney, L.M., Ozpolat, B.D., and Wessely, O. (2007). Xenopus Bicaudal-C is required for the differentiation of the amphibian pronephros. Dev. Biol. 307, 152-164.
Urban, A.E., Zhou, X., Ungos, J.M., Raible, D.W., Altmann, C.R., and Vize, P.D. (2006). FGF is essential for both condensation and mesenchymal-epithelial transition stages of pronephric kidney tubule development. Dev. Biol. 297, 103-117.
Yang, C.L., Zhu, X., and Ellison, D.H. (2007). The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex. J. Clin. Invest. 117, 3403-3411.
Zhou, X., and Vize, P.D. (2004). Proximo-distal specialization of epithelial transport processes within the Xenopus pronephric kidney tubules. Dev. Biol. 271, 322-338.
Xenopus Grants funding by the NIDDK
According to NIH RePORTER Search Tool, in the fiscal year of 2009, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) funded 53 grants for projects involving Xenopus. These grants total $11,307,900.� See appendix for complete list.
2009 Xenopus White Paper � Community Needs
Executive Summary
Xenopus - a crucial model organism for biomedical research:
Experiments in model animals are a cornerstone of biomedical research and have a massive impact on our understanding of human health and disease.� The frog, Xenopus, is a widely used and crucial vertebrate model organism that offers a unique combination of three powerful advantages:� strong conservation of essential biological mechanisms, a remarkable experimental repertoire, and unparalleled cost-effectiveness when compared to murine or other mammalian models.�
In fact, for many experimental applications, Xenopus is the only viable model system.� For example, in cell and molecular biology, Xenopus extracts allow for individual components of the cell cycle or DNA replication/repair machinery to be analyzed in a manner that cannot be recapitulated in vivo or in cell culture.� For developmental biology, no other model system allows for high-throughput genomic/proteomic screening and at the same time allows for transplant/explant analysis (i.e. �experimental embryology�).� The Xenopus oocyte is unique as a system for studying channel physiology using the patch-clamp and as a system for protein expression.� Finally, Xenopus is the only vertebrate model that readily produces enough biological material for biochemical purification from eggs, intact embryos, or isolated embryonic tissues.� The combination of these characteristics offers a wide range of experimental opportunities for studies using the Xenopus system in contrast to other vertebrates such as the mouse or zebrafish.
NIH Investment in Xenopus:
����������� The NIH has made a substantial and continuing investment in Xenopus research.� Indeed, a search of the NIH rePORT database for R01�s or equivalent grants using the search term �Xenopus� returned 427 grants for a total cost of $127,583,776 for FY08 and FY09.� Despite this investment in individuals� research, the Xenopus community lacks many resources that are considered entirely essential for other model systems, including a complete genome sequence, stock and training centers, and a comprehensive model organism database.
Xenopus as a Model System and Human Disease:
Given the tremendous advantages of the Xenopus system, the pace of new biological discovery by the Xenopus Community is brisk.� Using Xenopus, we have significantly improved our understanding of human disease genes and their mechanisms, justifying the NIH�s investment in Xenopus.� Below we provide examples of just a few of the human health discoveries made in the last two years:
Xenopus embryos are used for in vivo analysis of gene expression and function:
Nephronophthisis - Hum Mol Genet. 2008. 17, 3655-62; Nat Genet. 2005. 37, 537-43.
Cutis laxa - Nat Genet. 2009. 41, 1016-21.
Meckel-Gruber syndrome - Am J Hum Genet. 2008. 82, 959-70.
Colorectal cancer - Genome Res. 2009.� 19, 987-93.
Xenopus egg extracts are used for in vitro biochemical studies:
Fanconi Anemia - Mol. Cell. 2009. 35, 704-15;� J Biol Chem. 2009, 284, 25560-8.
C-myc oncogene - Nature. 2007. 448, 445-51.
BRCA1 - Cell. 2006. 127, 539-552
Xenopus oocytes are used to study gene expression and channel activity:
Trypanosome transmission - Nature 2009. 459, 213-217.
Epilepsy, ataxia, sensorineural deafness - N Engl J Med. 360, 1960-70.
Catastrophic cardiac arrhythmia (Long-QT syndrome) - PNAS �2009. 106,13082-7.
Megalencephalic leukoencephalopathy - Hum Mol Genet. 2008. 17, 3728-39.
Xenopus as a Model System and Basic Biological Processes:
Xenopus also plays a crucial role in elucidating the basic cellular and biochemical mechanisms underlying the entire spectrum of human pathologies.� Again only a few of the many discoveries in the last two years are highlighted here:
Xenopus embryos were used for studies of TGF-� signal transduction.
(Cell. 2009. 136,123-35; Science. 2007. 315, 840-3).
Xenopus egg extracts revealed fundamental aspects of cell division.
(Nature. 2008. 453, 1132-6; Science. 2008. 319, 469-72).
Xenopus embryos were used for studying mucociliary epithelia.
(Nat Genet. 2008. 40, 871-9; Nature. 2007. 447, 97-101).
Xenopus embryos were used for studying development of the vasculature.
(Cell. 2008.135, 1053-64).
Xenopus egg extracts provided key insight into DNA damage responses. �
(Mol Cell.� 2009. 35,704-15; Cell. 2008. 134, 969-80).
Xenopus embryos linked telomerase to Wnt signaling.
(Nature. 2009. 460, 66-72).
Xenopus was used for small molecule screens to develop therapeutics.
(Nat Chem Biol. 2008. 4, 119-25; Blood. 2009. 114, 1110-22).
Immediate Needs of the Xenopus Community:
����������� It is the consensus of the Xenopus community that their biomedical research could be greatly accelerated by the development of key resources that are currently lacking.� These resources would be of use to the entire Xenopus research community.� In this White Paper, the community identifies seven resources in two categories: Three Immediate Needs and four Essential Resources:
The Immediate Needs are a common set of key resources that were identified as the most pressing by three committees established to identify needed resources across the broad and diverse Xenopus community.� There is a broad, community-wide consensus that these resources would have an immediate impact on all Xenopus users and should be assigned the highest priority in order to accelerate the pace of biomedical research using Xenopus as a model system.�
����������� These Immediate Needs and the resulting improvements in biomedical research are as follows:
1.� Establishment of the Xenopus Resource and Training Center at the MBL in Woods Hole.
-Will allow rapid distribution of transgenic Xenopus laevis lines expressing fluorescent reporters and tagged proteins (for example histone-RFP for visualizing the mitotic spindle or organ specific GFP in embryos)
-Will allow centralized generation, housing, and distribution of genetically modified X. tropicalis lines, including both mutants and transgenics.
-Will allow both current investigators and the next generation of researchers to get hands-on training in� Xenopus-based biomedical research methods (including cell, molecular, and developmental methods).
2.� Expansion and improvement of Xenbase, a Xenopus model organism database.
-Maintain and curate data for the essential primary database for Xenopus researchers.
-Enhance the functionality of Xenbase by introducing a phenotypes feature.
-Support new content on Xenbase, including proteomics support, a new genome browser, and Wiki for Xenopus methods.
-Continue and expand collaborative and service efforts (e.g. provide Xenopus data to other databases including NCBI, UniProtK, Mascot and Tornado).
3.� Complete sequencing of the Xenopus laevis genome.
-Will allow the deconvolution of data in mass-spectrometry-based proteomic studies.
-Will facilitate identification of conserved gene regulatory regions to build gene-regulatory networks.
-Will facilitate site-specifc studies of DNA transaction (repair and replication)
-Will facilitate identification of all ORFs to build an ORFeome for rapid functional characterization of genes
-Will facilitate the design of morpholino oligonucleotides for gene depletion studies
-Will faciliate the analysis of chromatin-immunoprecipitations to identify DNA-bound to transcription factors and DNA modifications.
Essential Resources Needed by the Xenopus Community:
����������� In addition to these immediate, community-wide needs, the committees identified four Essential Resources that should be developed as soon as possible, so that Xenopus biologists can more effectively fulfill the missions of the NIH.� The Xenopus community considers all four of these additional resources to be essential, but understands that priorities must be set, and ranks these behind the Immediate Needs. These Essential Resources are as follows:
4.� Xenopus ORFeome in recombineering vectors.��
5.� Improvement of the X. tropicalis genome sequence and annotation
6.� Development of methods for disrupting gene function in Xenopus.
7. �Generation and Distribution of antibodies for Xenopus research.
Anticipated Gains for Biomedical Research:
����������� Xenopus is a crucial model organism for biomedical research.� With the development of large-scale community-wide resources, Xenopus is poised to be become the premier vertebrate model for systems-level approaches to understanding biological mechanisms in cell, molecular, and developmental biology.
The National Research Council and the National Academy of Sciences have recently called on the Unites States �to launch a new multiagency, multiyear, and multidisciplinary initiative to capitalize on the extraordinary advances recently made in biology�.� This report (http://www.nap.edu/catalog.php?record_id=12764) recommends the term "new biology" to describe an approach to research where �physicists, chemists, computer scientists, engineers, mathematicians, and other scientists are integrated into the field of biology.�� The promise of systems-level analysis in Xenopus, combined with its already proven strengths, make Xenopus the ideal model organism for pursuing this �new biology.�
Genome improvements will provide Xenopus researchers with the ability to perform genome-wide screens for biological activities that will in turn allow the rapid assembly and analysis of gene regulatory networks.� The ORFeome will greatly facilitate such genome-wide screening by allowing all ORFs to be rapidly analyzed or large numbers of proteins to be tagged for analysis of protein-protein interaction or for in vivo visualization.� Using extracts and biochemical purification coupled with mass-spectrometry and genomic sequence, protein interactomes can be rapidly identified and validated.� Because Xenopus can be so easily manipulated and because vast amounts of biological material can be generated, cell-type specific interactomes can also be identified.� Large-scale genetic screens will identify important novel genes in developmental pathways, especially given the relatively simple genome of X. tropicalis compared to zebrafish.� Finally, the flexibility of both Xenopus extracts and embryos make this system ideal for chemical biology screens.� Identifying these gene-regulatory networks, interactomes, and novel genes will be only the first steps, of course.� The well-established power of Xenopus for rapid analysis of gene function will then allow deeply mechanistic analyses to complement the systems-level approaches described above.�
It is the combination of these characteristics that distinguishes Xenopus from other vertebrate model systems such as mouse and zebrafish and allows for a systems-level approach to understanding biological mechanisms.� The tremendous promise of the Xenopus model cannot be realized, however, without the immediate development of community-wide research resources.� This White Paper presents the needed resources, and we look to the NIH for guidance in how to best achieve these goals.�
For complete details of the 2009 Xenopus White Paper, please visit
Appendix
Xenopus Grants funded by the NIDDK
|
Project Number |
Activity |
Project Title |
Principal Investigator |
Organization |
FY Total Cost by IC |
|
|
5R01DK062348-07 |
R01 |
CNS ACTION OF APPETITE SUPPRESSANT AMINOSTEROL |
AHIMA, REXFORD S |
UNIVERSITY OF PENNSYLVANIA |
$307,242 |
|
|
3R01DK062348-06S1 |
R01 |
CNS ACTION OF APPETITE SUPPRESSANT AMINOSTEROL |
AHIMA, REXFORD S |
UNIVERSITY OF PENNSYLVANIA |
$18,270 |
|
|
5R01DK067214-05 |
R01 |
FUNCTIONS OF THE HUMAN OST-ALPHA AND OST-BETA PROTEINS |
BALLATORI, NAZZARENO |
UNIVERSITY OF ROCHESTER |
$281,862 |
|
|
5K08DK078361-03 |
K08 |
ROLE OF THE RENAL SODIUM-PHOSPHATE CO-TRANSPORTER NAPI-IIC IN PHOSPHATE HOMEOSTAS |
BERGWITZ, CLEMENS |
MASSACHUSETTS GENERAL HOSPITAL |
$137,970 |
|
|
5K08DK068226-06 |
K08 |
SODIUM CHLORIDE COTRANSPORTER REGULATION BY WNK KINASE |
CAI, HUI |
EMORY UNIVERSITY |
$128,250 |
|
|
5P01DK017433-37 |
P01 |
CELLULAR AND MOLECULAR STUDIES OF RENAL TRANSPORT |
CAPLAN, MICHAEL J |
YALE UNIVERSITY |
$1,097,195 |
|
|
5R21DK080431-02 |
R21 |
ISOLATION AND CHARACTERIZATION OF RAT KIDNEY ACTIVE UREA TRANSPORTER |
CHEN, GUANGPING |
EMORY UNIVERSITY |
$193,750 |
|
|
5R01DK044158-19 |
R01 |
MYC ROLE IN HEMATOPOIESIS, VASCULOGENESIS & AGIOGENESIS |
CLEVELAND, JOHN L. |
SCRIPPS RESEARCH INSTITUTE |
$345,824 |
|
|
2R01DK062914-05A2 |
R01 |
CELL SIGNALING IN DEVELOPING EPITHELIA |
DRESSLER, GREGORY R |
UNIVERSITY OF MICHIGAN AT ANN ARBOR |
$347,625 |
|
|
5R01DK051496-11 |
R01 |
REGULATION OF THIAZIDE-SENSITIVE NACL TRANSPORT |
ELLISON, DAVID H. |
OREGON HEALTH AND SCIENCE UNIVERSITY |
$277,817 |
|
|
5R01DK032753-26 |
R01 |
MECHANISMS OF TRANSPORT IN PROXIMAL AND DISTAL TUBULES |
GUGGINO, WILLIAM B. |
JOHNS HOPKINS UNIVERSITY |
$348,500 |
|
|
3R01DK032753-25A1S1 |
R01 |
MECHANISMS OF TRANSPORT IN PROXIMAL AND DISTAL TUBULES |
GUGGINO, WILLIAM B. |
JOHNS HOPKINS UNIVERSITY |
$16,400 |
|
|
3P01DK061521-05S1 |
P01 |
TISSUE CULTURE CORE |
GUNN, ROBERT B |
EMORY UNIVERSITY |
$2,021 |
|
|
5R01DK059913-09 |
R01 |
NONGENOMIC STEROID SIGNALING IN OOCYTES |
HAMMES, STEPHEN R |
UNIVERSITY OF ROCHESTER |
$300,470 |
|
|
5K08DK067245-06 |
K08 |
MECHANISMS OF REGULATION OF ANION EXCHANGER SLC26A6 |
HASSAN, HATIM A |
UNIVERSITY OF CHICAGO |
$142,020 |
|
|
5K08DK070668-05 |
K08 |
REGULATION OF THE SODIUM CHLORIDE COTRANSPORTER |
HOOVER, ROBERT S |
UNIVERSITY OF CHICAGO |
$125,010 |
|
|
5R01DK077197-03 |
R01 |
TRANSCRIPTIONAL REGULATORY NETWORKS CONTROLLING XENOPUS PANCREAS DEVELOPMENT |
HORB, MARKO E |
CLINICAL RESEARCH INSTITUTE OF MONTREAL |
$195,804 |
|
|
5R01DK064572-07 |
R01 |
MECHANISMS FOR ALTERED GLUCOSE HOMEOSTASIS DURING HAART |
HRUZ, PAUL W |
WASHINGTON UNIVERSITY |
$297,920 |
|
|
3R01DK064572-07S1 |
R01 |
MECHANISMS FOR ALTERED GLUCOSE HOMEOSTASIS DURING HAART |
HRUZ, PAUL W |
WASHINGTON UNIVERSITY |
$38,195 |
|
|
5R01DK069403-04 |
R01 |
ORIGIN AND REGULATION OF KIDNEY PROGENITOR CELLS |
HUKRIEDE, NEIL A |
UNIVERSITY OF PITTSBURGH AT PITTSBURGH |
$277,004 |
|
|
5F30DK082153-02 |
F30 |
FUNCTIONALLY PROBING HSGLT2 IN DIABETES TREATMENT AND GLUCOSE HOMEOSTASIS |
HUMMEL, CHARLES STANTON |
UNIVERSITY OF CALIFORNIA LOS ANGELES |
$30,826 |
|
|
5F32DK083160-02 |
F32 |
TRANSCRIPTIONAL REGULATION OF BETA-CELL-SPECIFIC EXPRESSION OF THE MAFA GENE |
HUNTER, CHAD S |
VANDERBILT UNIVERSITY |
$43,020 |
|
|
1R01DK082430-01 |
R01 |
HISTONE PROLINE ISOMERIZATION AND GENE REGULATION |
KIKYO, NOBUAKI |
UNIVERSITY OF MINNESOTA TWIN CITIES |
$377,500 |
|
|
5R37DK051391-14 |
R37 |
BIOMECHANICAL REGULATION OF RENAL ION TRANSPORTERS |
KLEYMAN, THOMAS R. |
UNIVERSITY OF PITTSBURGH AT PITTSBURGH |
$305,881 |
|
|
1R01DK081594-01A1 |
R01 |
IDENTIFICATION, CHARACTERIZATION AND REGULATION OFINTERMEDIATE CONDUCTANCE K CHAN |
LENG, QIANG |
YALE UNIVERSITY |
$400,847 |
|
|
1ZIADK053214-03 |
ZIA |
NOVEL APPROACHES TO OBESITY: MODULATION OF INTESTINAL GLUCOSE ABSORPTION |
LEVINE, MARK J |
|
$176,155 |
|
|
5R01DK080047-02 |
R01 |
DIVALENT METAL-ION TRANSPORTER DMT1 AND ITS ROLE IN INTESTINAL METAL-ION UPTAKE |
MACKENZIE, BRYAN |
UNIVERSITY OF CINCINNATI |
$273,000 |
|
|
3R01DK080047-02S2 |
R01 |
DIVALENT METAL-ION TRANSPORTER DMT1 AND ITS ROLE IN INTESTINAL METAL-ION UPTAKE |
MACKENZIE, BRYAN |
UNIVERSITY OF CINCINNATI |
$35,846 |
|
|
5R01DK030111-27 |
R01 |
REGULATION OF HORMONE-SENSITIVE EFFECTOR SYSTEMS |
MALBON, CRAIG C |
STATE UNIVERSITY NEW YORK STONY BROOK |
$374,964 |
|
|
5F32DK082145-02 |
F32 |
NON-CANONICAL WNT SIGNALS IN KIDNEY TUBULOGENESIS |
MILLER, RACHEL KATHERINE |
UNIVERSITY OF TEXAS MD ANDERSON CAN CTR |
$50,054 |
|
|
5F32DK082154-02 |
F32 |
AN INVESTIGATION OF THE RENAL NA-K-CI COTRANSPORTER |
MONETTE, MICHELLE YVONNE |
YALE UNIVERSITY |
$50,054 |
|
|
2R01DK062277-06 |
R01 |
ROLE OF WNT/BETA-CATENIN SIGNALING IN LIVER DEVELOPMENT |
MONGA, SATDARSHAN SINGH |
UNIVERSITY OF PITTSBURGH AT PITTSBURGH |
$442,957 |
|
|
3P01DK070756-03S1 |
P01 |
EPITHELIAL OXALATE AND CITRATE TRANSPORT |
MOUNT, DAVID BRUCE |
BRIGHAM AND WOMEN'S HOSPITAL |
$46,596 |
|
|
3P30DK034989-25S1 |
P30 |
CORE--MORPHOLOGY CORE |
NATHANSON, MICHAEL H |
YALE UNIVERSITY |
$98,046 |
|
|
5R01DK079784-02 |
R01 |
MECHANISM OF FETAL AND NEONATAL HANDLING OF HIV DRUGS |
NIGAM, SANJAY K |
UNIVERSITY OF CALIFORNIA SAN DIEGO |
$328,313 |
|
|
5K08DK073487-05 |
K08 |
THE FUNCTIONAL ROLE OF THE PXL DOMAIN OF SGK1 IN EPITHELIAL SODIUM TRANSPORT |
PAO, ALAN C |
STANFORD UNIVERSITY |
$119,530 |
|
|
5R01DK056695-08 |
R01 |
SGK REGULATION OF EPITHELIAL SODIUM TRANSPORT |
PEARCE, DAVID |
UNIVERSITY OF CALIFORNIA SAN FRANCISCO |
$301,389 |
|
|
3R01DK056695-08S1 |
R01 |
SGK REGULATION OF EPITHELIAL SODIUM TRANSPORT |
PEARCE, DAVID |
UNIVERSITY OF CALIFORNIA SAN FRANCISCO |
$109,574 |
|
|
5R01DK072154-03 |
R01 |
INTERPLAY OF RENAL CA AND NA TRANSPORT PATHWAYS |
PENG, JI-BIN |
UNIVERSITY OF ALABAMA AT BIRMINGHAM |
$262,175 |
|
|
5K01DK080194-02 |
K01 |
AN EPITHELIAL MODEL FOR V-TYPE H+-ATPASE-DRIVEN ACID-BASE TRANSPORT |
PIERMARINI, PETER M |
CORNELL UNIVERSITY ITHACA |
$105,854 |
|
|
3K01DK080194-02S1 |
K01 |
AN EPITHELIAL MODEL FOR V-TYPE H+-ATPASE-DRIVEN ACID-BASE TRANSPORT |
PIERMARINI, PETER M |
CORNELL UNIVERSITY ITHACA |
$54,000 |
|
|
5K99DK081610-02 |
K99 |
OLFACTORY PROTEINS IN THE KIDNEY AND REGULATION OF GLOMERULAR FILTRATION RATE |
PLUZNICK, JENNIFER L |
YALE UNIVERSITY |
$88,354 |
|
|
5K08DK069608-05 |
K08 |
MOLECULAR BASIS OF BLADDER ORGANOGENESIS |
REDDY, PRAMOD P |
CHILDREN'S HOSPITAL MED CTR (CINCINNATI) |
$125,010 |
|
|
5K01DK078679-03 |
K01 |
THE FUNCTIONAL ROLE OF GILZ IN EPITHELIAL SODIUM TRANSPORT |
SOUNDARARAJAN, RAMA |
UNIVERSITY OF CALIFORNIA SAN F RANCISCO |
$124,200 |
|
|
3R21DK077763-02S1 |
R21 |
MICRORNAS IN KIDNEY DEVELOPMENT |
WESSELY, OLIVER |
LOUISIANA STATE UNIV HSC NEW ORLEANS |
$3,845 |
|
|
1R01DK080745-01A2 |
R01 |
THE ROLE OF BICAUDAL-C IN POLYCYSTIC KIDNEY DISEASE |
WESSELY, OLIVER |
LOUISIANA STATE UNIV HSC NEW ORLEANS |
$340,800 |
|
|
5F30DK082121-02 |
F30 |
GENE REGULATORY NETWORK FOR PODOCYTE DEVELOPMENT |
WHITE, JEFFREY THOMAS |
LOUISIANA STATE UNIV HSC NEW ORLEANS |
$28,874 |
|
|
5R01DK068258-05 |
R01 |
PURINERGIC NEUROGENIC MUCOSAL SECRETION |
WOOD, JACKIE D. |
OHIO STATE UNIVERSITY |
$277,835 |
|
|
5R01DK077133-02 |
R01 |
ROLE OF SGLTS IN GLUCOSE HOMEOSTASIS AND TISSUE METABOLISM |
WRIGHT, ERNEST M |
UNIVERSITY OF CALIFORNIA LOS ANGELES |
$327,250 |
|
|
5R01DK043955-19 |
R01 |
MECHANISMS OF WATER FLOW ACROSS BIOLOGICAL MEMBRANES |
ZEIDEL, MARK L. |
BETH ISRAEL DEACONESS MEDICAL CENTER |
$330,216 |
|
|
5R01DK070858-03 |
R01 |
MOLECULAR BASIS OF LIVER DEVELOPMENT |
ZORN, AARON M |
CHILDREN'S HOSPITAL MED CTR (CINCINNATI) |
$301,350 |
|
|
1R01DK080823-01A1 |
R01 |
MAMMALIAN FOREGUT AND LIVER DEVELOPMENT |
WELLS, JAMES M;ZORN, AARON M ; |
CHILDREN'S HOSPITAL MED CTR (CINCINNATI) |
$394,437 |
|
|
3R01DK080823-01A1S1 |
R01 |
MAMMALIAN FOREGUT AND LIVER DEVELOPMENT |
WELLS, JAMES M;ZORN, AARON M ; |
CHILDREN'S HOSPITAL MED CTR (CINCINNATI) |
$99,999 |
|
|
|
|
|
|
Total |
$11,307,900 |
|