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Kristi Wharton, PHD, MS, MPhil

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Kristi Wharton

Title: Professor of Medical Science
Department: Molecular Biology, Cell Biology, & Biochemistry

Kristi_Wharton@Brown.EDU
+1 401 863 1951

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Overview | Research | Grants/Awards | Teaching | Publications

The goal of the research in our laboratory is to understand how TGF-B signaling molecules facilitate the communication between cells. Cellular communication is essential to the proper manifestation of cell movements, growth, and differentiation during the development of multi-cellular organisms.

Biography

EDUCATION
1978 A.B. Biology
School of Arts and Sciences, Cornell University, Ithaca, NY

1986 Ph.D. Biology
Yale University, New Haven, CT

PROFESSIONAL APPOINTMENTS

1981 - 1986 Graduate Student
Biology Department
Yale University
Mentor: Spyros Artavanis-Tsakonas

1986 - 1987 Postdoctoral Fellow
Biology Department
Yale University
Mentor: Spyros Artavanis-Tsakonas

1987 Postdoctoral Fellow
Institute of Molecular Biology and Biotechnology
Crete, Greece
Mentors: Fotis Kafatos and Christos Louis

1988 - 1991 Postdoctoral Fellow
Cell and Developmental Biology
Harvard University
Mentor: William Gelbart

1991 - 1995 Assistant Professor (Research)
Division of Biology and Medicine
Department of Molecular Biology, Cellular Biology and Biochemistry
Brown University

1995 - 2001 Assistant Professor of Medical Sciences
Department of Molecular Biology, Cellular Biology and Biochemistry
Brown University

2000 - 2001 Manning Assistant Professor
Department of Molecular Biology, Cellular Biology and Biochemistry
Brown University

2003 Department of Cell Biology
Biozentrum, University of Basel, Switzerland
(sabbatical leave from Brown University, Spr 2003)

2001-2012 Associate Professor of Medical Sciences
Department of Molecular Biology, Cellular Biology and Biochemistry
Brown University

2010 Departement Genetique et Developpement
Institut de Genetique Humaine, CNRS Montpellier, France
(sabbatical leave from Brown University, Spr 2010)
2012 - present Professor of Medical Sciences
Department of Molecular Biology, Cell Biology and Biochemistry
Brown University

2005 Elizabeth Leduc Award for Excellence in
Teaching in the Life Sciences

Institutions

Bu

Research Description

The goal of the research in our laboratory is to understand how TGF-B signaling molecules facilitate the communication between cells. Cellular communication is essential to the proper manifestation of cell movements, growth, and differentiation during the development of multi-cellular organisms. Secreted proteins, such as those which belong to the transforming growth factor-B (TGF-B ) superfamily, are thought to mediate intercellular communication through their binding and/or association with integral membrane proteins. The transmission of such a signal culminates in the activation or repression of gene expression in the responding cell, resulting in alterations in the cell's phenotype, its position in the cell cycle, the types or extent of proteins expressed on the cell's surface, and/or in further transcription of new sets of genes. TGF-B -related proteins have been identified in both vertebrates and invertebrates as signaling factors which are instrumental in the control of cellular growth and differentiation, as well as in inductive events that specify cell fates. In order to understand the control of cellular growth and differentiation central to normal development, it is important to elucidate the regulation and molecular and cellular mechanisms of TGF-B signaling. Our approach to elucidating these signaling mechanisms is to exploit the genetic, molecular, and cell biological techniques of Drosophila to analyze the genes and their products, which act in TGF-B-type signaling pathways, and to investigate the function and regulation of these molecules in vivo.

To initiate this research program and as a means toward understanding the specificity of TGF-B -related signaling molecules, we have identified a new Drosophila member of the superfamily, the 60A gene. As a first step toward understanding 60A function, we have generated mutations in the locus. The phenotype of 60A mutants coupled with its wild type expression pattern suggest that 60A is important in multiple developmental processes. We are currently analysing the role of 60A in these processes, as well as beginning to identify other components of the signaling pathway which mediates the 60A signal. It will be of particular interest to compare the action and signaling pathway of 60A with that of decapentaplegic, dpp, which is probably the TGF-B family member best understood in terms of in vivo function.

Awards

NIH NRSA Training grant in Genetics, 1982-1986
Sessil B. Anonymous Fellowship, Yale University, 1986-87
EMBO Short Term Fellowship, IMBB, Crete, Greece, 1987
NIH NRSA Postdoctoral Fellowship, Harvard University, 1988-1991
American Heart Association Established Investigatorship, Brown University, 1994-1999
Manning Assistant Professor, Brown University, 2000
Elizabeth H. Leduc Award for Excellence in Teaching in the Life Sciences, Brown University, 2005

Affiliations

Panel member: Academy of Finland, Biosciences panel, Helsinki, Sept. 18-21, 2005

Panel member: American Cancer Society – Peer Review Committee on Development, Differentiation, and Cancer, Jan. 1, 2001–Dec. 31, 2005

Memberships: Genetics Society of America, Sigma Xi, Society of Developmental Biology

Funded Research

CURRENT

National Institutes of Health - RO1 GM068118-01A2
Total project period: 02/01/2005–01/31/2009
Total direct costs: $1,178,895
Role in project: PI
Title of project: "Differential regulation of BMP signals in vivo"

PAST

Richard B. Salomon Faculty Research Award
Brown University
Office of the Vice President for Research
Total project period: 02/01/2004–07/01/2005
Total direct costs: $15,000
Role in project: PI
Title of project: "Establishing assays to investigate BMP ligand type and receptor choice"

NIH/NCRR - 1 P20 RR15578-01
COBRE
Center for Genetics and Genomics (Sedivy, J.-PI)
Total project period: 09/30/2000–08/31/2005
Total direct costs for current year: $1,590,251
Role in project: Investigator (K. Wharton)
Title of project: "Mechanism of BMP signaling"

American Cancer Society - RPG DDC-98790
Total project period: 07/01/1999-06/30/2002
Total costs: $300,700 (direct), $74,300 (indirect)
Title of Project: "Functional analysis of signaling by multiple TGF-/BMP ligands"

National Science Foundation - IBN-9604769
Total project period: 03/15/1997-08/31/1999
Total costs: $129,018 (direct), $74,161 (indirect)
Title of Project: "Analysis of TGF-/BMP-mediated Signaling"

American Heart Association - Established Investigatorship 94002580
Total project period: 07/01/1994-06/30/1999
Total costs: $306,760 (direct)
Title of project: "Functional Analysis of TGF--mediated Cellular Signaling"

Salomon Faculty Research Award
Total project period: 02/01/1996-01/31/1997
Total costs: $15,000 (direct)
Title of project: "TGF-β-mediated signaling during oogenesis"

National Science Foundation - IBN-9205808
Total project period: 09/01/1992-08/31/1996
Total costs: $181,508 (direct), $100,492 (indirect)
Title of project: "Cellular communication during Drosophila development"

American Cancer Society - DB-32
Total project period: 01/01/1993-12/31/1995
Total costs: $145,723 (direct), $34,277 (indirect)
Title of project: "TGF- cell signaling during development"

NECUSE –The New England Consortium for Undergraduate Science Education/
The Pew Charitable Trusts
Support for two Brown undergraduates to attend Annual Drosophila Conference
Awarded: 12/13/1993
Total costs: $1,690

American Cancer Society - Institutional Award
Total project period: 08/01/1991-06/30/1993
Total costs: $9,000 (direct)
Title of project: "Functional analysis of a TGF--like gene during development"

Courses Taught

  • Analysis of Development (BI0131)
  • Topics in Developmental Biology (BI0233)
  • Topics in Developmental Biology (BI0232)
  • Vertebrate Embryology (BI0032)

View My Full Publication List in pdf format

Selected Publications

  • Ballard, S., Jarolimova, J. and Wharton, K.A. (2010) Gbb/BMP signaling is required to maintain energy homeostasis in Drosophila. Developmental Biology 337, 375-85. PMID: 19914231(2010)
  • Twombly, V., Bangi, E., Le, V.Q., Malnic, B., Singer, M. and Wharton, K.A. (2009). Functional analysis of saxophone, the Drosophila BMP type I receptor ortholog of human ALK1/ ACVRL1 and ACVR1/ALK2. Genetics 183, 563-79. PMID: 19620392(2009)
  • Wharton, K.A. and Derynck, R. (2009) TGF-β family signaling: Novel insights in development and disease. Development 136, 3691-97. PMID: 19855012 (invited review)(2009)
  • Prabhat, Forsberg, A., Katzourin, M., Wharton, K.A. and Slater, M (2007). A Comparative Study of Desktop, Fishtank and Cave Systems for the Exploration of Volume Rendered Confocal Data Sets. IEEE Transactions on Visualization and Computer Graphics, epub. 06 Aug 2007. PMID: 18461742 http://doi.ieeecomputersociety.org/10.1109/TVCG.2007.70433(2007)
  • Bangi, E. and Wharton, K.A. (2006) Dpp and Gbb exhibit different effective ranges in the establishment of the BMP activity gradient critical for Drosophila wing patterning. Developmental Biology 295, 178-93. PMID: 16643887(2006)
  • Bangi, E. and Wharton, K. A. (2006). Dual function of the Drosophila ALK1/ALK2 orthologue, Saxophone, influences the BMP activity gradient critical for wing patterning. Development 133, 3295-303. PMID: 16887821(2006)
  • Sinenko, S.A., Kim, E.K., Wynn, R., Manfruelli, P., Ando, I., Wharton, K.A., Perrimon, N. and Mathey-Prevot, B. (2004). Yantar is a novel and evolutionary conserved gene involved in Drosophila hemocyte differentiation. Developmental Biology 273: 48-62. PMID: 15302597(2004)
  • Ray, R.P. and Wharton, K.A. (2001) Twisted perspective: New insights into extracellular modulation of BMP signaling during development. Cell 104, 801-804. (invited review)(2001)
  • Ray, R. and Wharton, K. A. (2001). Context-dependent relationships between the BMPs gbb and dpp during development of the Drosophila wing imaginal disc. Development 128, 3913-25. PMID: 11641216(2001)
  • Wharton, K. A., Cook, J., Torres-Schumann, S., de Castro, K., Borod, E., Phillips, D. A., (1999). Genetic analysis of the BMP-related gene, gbb, identifies multiple requirements during Drosophila development. Genetics 152: 629-40. PMID: 10353905(1999)
  • Haerry, T. E., Khalsa, O., O'Connor, M. B., Wharton, K. A., (1998). Synergistic signaling by two BMP ligands through the SAX and TKV receptors controls wing growth and patterning in Drosophila. Development 125: 3977-87. PMID: 9735359(1998)
  • Khalsa, O., Yoon, J-W., Torres-Schumann, S., Wharton, K.A., (1998). TGF-β/BMP superfamily members, Gbb-60A and Dpp,cooperate to provide pattern information and establish cell identity in the Drosophila wing. Development 125: 2723-34. PMID: 9636086(1998)
  • Wharton, K.A., Ray, R.P., Findley, S.D., Duncan, H.E. and Gelbart, W.M. (1996) Molecular lesions associated with alleles of decapentaplegic identify residues necessary for TGF-β/ BMP cell signaling in Drosophila melanogaster. Genetics 142, 493-505. PMID: 8852848(1996)
  • Raftery, L.A., Twombly, V., Wharton, K.A. and Gelbart, W.M. (1995) Genetic screens to identify elements of the decapentaplegic signaling pathway in Drosophila. Genetics 139, 241-54. PMID: 7705627(1995)
  • Wharton, K. A. (1995) How many receptors does it take? Bioessays 17, 13-16.(1995)
  • Wharton, K.A., Ray, R. and Gelbart, W.M. (1993) An activity gradient of decapentaplegic is required for dorsal-ventral patterning in the Drosophila embryo. Development 117, 807-22. PMID: 8330541(1993)
  • Wharton, K.A., Thompsen, G.and Gelbart, W.M. (1991) Drosophila 60A gene, a TGF-β family member, is closely related to human bone morphogenetic proteins. PNAS 88, 2914-18. PMID: 1924384(1991)
  • Ramos, R.G.P., Grimwade, B.G., Wharton, K.A., Scottgale, T.N. and Artavanis-Tsakonas, S. (1989) Physical and functional definition of Drosophila Notch locus by P -element transformation. Genetics 123, 337-48. PMID: 2555253(1989)
  • Yedvobnick, B., Muskavitch, M.A.T., Wharton, K.A., Halpern, M.E., Paul, E., Grimwade, B.G., and Artavanis-Tsakonas, S. (1985) Molecular genetics of Drosophila neurogenesis. Cold Spring Harbor Sympos.Quant.Biology 50:841-854.(1985)
  • Artavanis-Tsakonas, S., Grimwade, B., Halpern, M.E., Johansen, K. Markopoulou, K., Ramos, R.G.P. Schlesinger-Bryant, R., Wharton, K.A. and Yedvobnick, B. (1985) Molecular biology of genes involved in the neurogenesis of Drosophila. Society for Developmental Biology 44th Annual Symposium. ed. Joseph Gall(1985)
  • Wharton, K.A., Johansen, K.M., Xu, T. and Artavanis-Tsakonas, S. (1985) Nucleotide sequence from the neurogenic locus Notch implies a gene product which shares homology with proteins containing EGF-like repeats. Cell 43, 567-81. PMID: 3935325(1985)
  • Wharton, K.A., Yedvobnick,B., Finnerty, V.G. and Artavanis-Tsakonas, S. (1985) opa: A novel family of transcribed repeats shared by the Notch locus and other developmentally regulated loci in Drosophila melanogaster. Cell 40: 55-62. PMID: 2981631(1985)
  • Artavanis-Tsakonas, S., Grimwade, B.G., Harrison, R.G., Markopoulou, K.,Muskavitch, M.A.T., Schlesinger-Bryant, R., Wharton, K.A. and Yedvobnick, B. (1984) The Notch locus of Drosophila melanogaster: A molecular analysis. Developmental Genetics 4: 233-254.(1984)
  • Mooseker, M.S., Bonder, E.M., Grimwade, B.G., Howe, C.L., Keller, T.C.S., Wasserman,R.H. and Wharton, K.A. (1982) Regulation of contractility, cytoskeletal structure and filament assembly in brush borders of the intestinal epithelial cells. Cold Spring Harbor Sympos.Quant.Biology 46: 855-870.(1982)
  • Mooseker, M.S., Pollard, T.D. and Wharton, K.A. (1982) Nucleated polymerization of actin from the two ends of microvillar filaments in the intestinal brush border. J.Cell Biol. 95:223-233.(1982)