Dr. Jeffrey Hildebrand

Genetics
K. Arndt
T.-L. Ashman
G. Campbell
D. Chapman
G. Hatfull
J. Hildebrand
L. Jacobson
S. Kalisz
J. Martens
V. Oke
W. Saunders
B. Stronach
S. Tonsor
R. Wood

Microbiology
G. Hatfull
R. Hendrix
J. Lawrence
V. Oke
J. Pipas
M. Popa
I. Campbell
R.L. Duda
S. Godfrey

Molecular Biology
K. Arndt
J. Franzen
P. Grabowski
G. Hatfull
R. Hendrix
L. Jen-Jacobson
J. Martens
C. Peebles
J. Pipas
J. Rosenberg
A. Schwacha
C. Walsh

Plant Biology
T.-L. Ashman
W. Carson
S. Kalisz
V. Oke
C. Partanen
S. Tonsor
B. Traw

Science Education
A. Bledsoe
K. Curto
L. Daniels
S. Godfrey
N. Kaufmann
C. LaFave
J. Newman
E. Polinko
M. Popa
L. Roberts
T. Seiflein
R. Sherwin
A. Slinskey Legg

Structural Biology
M. Grabe
J. Hempel
R. Hendrix
L. Jen-Jacobson
J. Rosenberg
A. VanDemark

Former Faculty

Photo of Dr.
Hildebrand

Cell Biology and Genetics of Mouse Development

Associate Professor

Dr. Hildebrand received his Ph.D. in 1995 with J. Thomas Parsons at the University of Virginia, performed his postdoctoral studies with Philippe Soriano at the Fred Hutchinson Cancer Research Center, and joined the Department in 2000.

Currently, Dr. Hildebrand is accepting graduate students in his laboratory. Dr. Hildebrand is accepting undergraduate researchers, and does sponsor students in other laboratories.

Professional Interests - Publications - Contact Information - Lab Personnel

Professional Interests of Jeffrey Hildebrand

Research in my laboratory utilizes a combination of mouse molecular genetics, cell biology, biochemistry, and limited aspects of functional genomics to address fundamental issues of vertebrate development and disease. Of particular interest are molecular pathways that regulate cytoskeletal architecture and cell growth.

Shroom staining Cell architecture: The Shroom family of proteins.
During vertebrate development, cells utilize numerous mechanisms to maintain proper cytoplasmic, nuclear, and membrane architecture. These complex regulatory systems are central to processes such as cell migration, adhesion, and shape. In turn, these properties control aspects of cell identity, tissue morphogenesis, proliferation, gene expression, and apoptosis. One project in the lab focuses on a family of proteins, the Shroom(Shrm)/Apx family, implicated in cytoskeletal architecture. Shrm-deficient mouse embryos exhibit anomalies in neural tube closure that subsequently result in birth defects such as spina bifida, exencephaly, and facial clefting. Multiple lines of evidence indicate that Shrm is a cytoskeletal protein and altered cyto-architecture may be responsible for the observed phenotypes. First, Shrm is targeted to stress fibers and sites of cell-cell adhesion (see figure at right), directly binds F-actin, and causes the redistribution of F-actin in cells. Second, analysis of the neuroepithelium within shrm null embryos reveals altered distribution of several cytoskeletal proteins. Future work in the lab will continue to employ multiple approaches to study the molecular mechanisms that regulate cellular architecture and will utilize the Shrm family of proteins as a starting point. I am especially focused on characterizing additional Shrm-related proteins, identifying the cellular pathways and processes that utilize Shrm and Shrm-like proteins, determining the in vivo requirements for other Shrm family members, and solving the biological structure of the Shrm protein.

Growth and differentiation: The CtBP family of Proteins.
It is well documented that gene expression and cell proliferation are tightly controlled and that deregulation of these processes can be detrimental to embryonic and adult viability. The CtBP proteins appear to be critical regulators for both of these processes. While it is unclear how these proteins carry out such functions, CtBP has been shown to associate with, and mediate the activity of, several known transcription factors. To characterize the in vivo functions of these proteins during cell and developmental biology, mice harboring mutations in both ctbp1 and ctbp2 have been generated. Initial characterization of these mice suggests that CtBP1 and CtBP2 are required for multiple developmental processes, including formation of the placenta, muscle differentiation, and vascularization. In the immediate future, this project will focus on analyzing adult and embryonic phenotypes, identifying CtBP targets, and elucidating the molecular function of these proteins.

Publication Archive
25 Citations
23 Abstracts
23 PDFs

Recent Publications of Jeffrey Hildebrand

Yoder, M., and J.D. Hildebrand (2007) Shroom4 (KIAA1202) is an actin-associated protein implicated in cytoskeletal organization. Cell Motil. Cytoskel. 64:49-63 (PDF Reprint: 2.6 MB)

Hagens, O., A. Ballabio, V. Kalscheuer, J.P. Kraehenbuhl, M.V. Schiaffino, P. Smith, O. Staub, J. Hildebrand, and J.B. Wallingford (2006) A new standard nomenclature for proteins related to Apx and Shroom. BMC Cell Biol 7:18 (PDF Reprint: 189 kb)

Fairbank, P.D., C. Lee, A. Ellis, J.D. Hildebrand, J.M. Gross, and J.B. Wallingford (2006) Shroom2 (APXL) regulates melanosome biogenesis and localization in the retinal pigment epithelium. Development 133:4109-4118 (PDF Reprint: 3.8 MB)

Dietz, M.L., T.M. Bernaciak, F. Vendetti, and J.D. Hildebrand (2006) Differential actin-dependent localization modultes the evolutionarily conserved activity of shroom-family proteins. J. Biol. Chem. 281:20542-20554 (PDF Reprint: 1.7 MB)

Hildebrand, J.D. (2005) CtBP proteins in vertebrate development. Pp in CtBP Family Proteins, Chinnadurai, G., Ed. Landes Bioscience

Hildebrand, J.D. (2005) Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network. J. Cell Sci. 118:5191-5203 (PDF Reprint: 2.4 MB)

Haigo, S.L., J.D. Hildebrand, R.M. Harland, and J.B. Wallingford (2003) Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. Curr. Biol. 13:2125-2137 (PDF Reprint: 876 kb)

Zhang, Q., Y. Yoshimatsu, J. Hildebrand, S.M. Frisch, and R.H. Goodman (2003) Homeodomain Interacting Protein Kinase 2 Promotes Apoptosis by Downregulating the Transcriptional Corepressor CtBP. Cell 115:177-186 (PDF Reprint: 337 kb)

Lin, X., B. Sun, M. Liang, Y.Y. Liang, A. Gast, J. Hildebrand, F.C. Brunicardi, F. Melchior, and X.H. Feng (2003) Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding. Mol. Cell 11:1389-1396 (PDF Reprint: 402 kb)

Grooteclaes, M., Q. Deveraux, J. Hildebrand, Q. Zhang, R.H. Goodman, and S.M. Frisch (2003) C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs. Proc. Natl. Acad. Sci., USA 100:4568-4573 (PDF Reprint: 504 kb)

Hildebrand, J.D., and P. Soriano (2002) Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development. Mol. Cell. Biol. 22:5296-5307 (PDF Reprint: 1.8 MB)

Howell, B.W., T.M. Herrick, J.D. Hildebrand, Y. Zhang, and J.A. Cooper (2000) Dab1 tyrosine phosphorylation site relay positional signals during mouse brain development. Curr. Biol. 10:877-885 (PDF Reprint: 432 kb)

How to Contact Jeffrey Hildebrand

US Mail
University of Pittsburgh
Department of Biological Sciences
103A Life Sciences Annex
4249 Fifth Avenue
Pittsburgh, PA 15260

Phone, FAX, Internet
Office : (412) 624-6987
Lab : (412) 624-6987
FAX : (412) 624-4759
Email : jeffh+@pitt.edu
Web :

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