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About
Dr. Pamela Hoodless, PhD
Senior Scientist
- Associate Professor, Medical Genetics, University of British Columbia
- Faculty Member, Genetics Program, University of British Columbia
- Faculty Member, Developmental and Cell Biology, University of British
Columbia
- Faculty Member, Interdisciplinary Oncology Program, University of
British Columbia
- Faculty Member, Bioinformatics Training Program, CIHR
Education:
B.Sc, Biochemistry, Queen's University, 1985
PhD, Biochemistry, Queen's University, 1991
Research Interest
My lab is primarily interested in early events in mammalian development and the
signalling pathways that regulated these processes. All vertebrates start as
a single cell that undergoes a series of orchestrated cell divisions to form
an embryo. During development, one of the first steps is to create a plan
for the embryonic body with anterior-posterior, dorsal-ventral, and
left-right axes.
Establishing the body plan of an embryo requires complex cell-cell
communication networks. Organizing centers have been identified in the
embryo which act as initiating sources for signaling networks and direct
surrounding cells into appropriate patterns. Two distinct organizing centers
are found in early mammalian embryos, the anterior visceral endoderm (AVE),
which is required for head structures, and the node, which coordinates the
body. How these organizers are formed and how they function to pattern the
embryo remains poorly understood.
One family of growth factors implicated in embryonic patterning is the
transforming growth factor-β (TGFβ) family. This family can be subdivided
into three classes, the TGFβs, activin/nodals and bone morphogenetic
proteins (BMPs). These extracellular ligands bind to receptors on the cell
surface that activate intracellular signalling molecules and regulate
transcription of genes in the nucleus. Research in my laboratory is focused
on understanding the functions and mechanisms through which the TGFβ family
of ligands regulates developmental processes such as embryonic patterning.
In addition to examining specific pathways, we are also using genome
approaches to examine tissue differentiation during development. In
collaboration with the Genome Science Centre
at the BC Cancer Agency, we are generating an atlas of gene expression
profiles from various tissues throughout development using serial analysis
of gene expression (SAGE). This will produce a database in which the
patterns of gene expression can be quantitatively compared between different
developmental stages of a tissue and between different tissues. Data from
our project can be viewed and downloaded from our website:
www.mouseatlas.org
Publications
Hoffman BG, Robertson G, Zavaglia PB, Beach M, Cullum R, Lee S,
Soukhatcheva G, Li L, Wederell ED, Thiessen N, Bilenky M, Cezard
T, Tam A, Kamoh B, Birol I, Dai D, Zhao YJ, Hirst M, Verchere B,
Helgason CD, Marra MA, Jones SJM, Hoodless PA.
Locus co-occupancy, nucleosome positioning, and
H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and
PDX1-bound loci in islets and liver.
Genome Res 20(8): 1037-51, 2010.
View
Abstract
Hassan AS, Hou J, Wei W, Hoodless PA,
Expression of two novel transcripts in the mouse definitive endoderm.
Gene Expr Patterns 10:127-134, 2010.
View Abstract
McKnight K, Hou J,
Hoodless PA.
FoxH1 and FoxA2 are not required for formation of the midgut and
hindgut definitive endoderm.
Dev Biol 337: 471-481, 2010.
View Abstract
Vrljicak P, Chang AC, Morozova O,
Wederell ED, Niessen K, Marra MA, Karsan A, Hoodless PA. Genomic
Analysis Distinguishes Phases of Early Development of the Mouse
Atrio-Ventricular
Canal.
Physiol Genomics 40(3): 150-157, 2010.
View Abstract
Wederell ED, Bilenky M , Cullum R, Thiessen N, Dagpinar M, Delaney A,
Varhol R, Zhao YJ, Zeng T, Bernier B, Ingham M, Hirst M, Robertson G
Marra MA, Jones S, Hoodless PA.
Global Analysis of In Vivo
FoxA2 Binding Sites in Mouse Adult Liver Using Massively Parallel
Sequencing. Nuc Acids Res 36:
4549-4564, 2008.
View Abstract
Robertson AG, Bilenky M, Tam A, Zhao Y, Zeng T, Thiessen N, Cezard T,
Fejes A, Wederell E, Cullum R, Euskirchen G, Krzywinski M, Birol I,
Snyder M, Hoodless PA, Hirst
M, Marra MA, Jones SJM.
Genome wide relationship between histone H3 lysine 4 mono-and-tri
methylation and transcription factor binding.
Genome Res 18:1906-1917, 2008
View Abstract
Niessen K, Fu YX, Chang L, Wong F, McFadden D,
Hoodless PA & Karsan A.
Slug is a direct Notch target required for initiation of cardiac cushion
cellularization.
J
Cell Biol
182:315-25, 2008.
View Abstract
Hoffman
BG, Zavaglia B, Witzsche J, Ruiz de Algara T, Beach M, Hoodless PA,
Jones SJ, Marra MA, & Helgason CD. Identification of transcripts with
enriched expression in the developing and adult pancreas. Genome Biol 9
(6): R99, 2008.
View Article
Bowie MB,
Kent
DG, Dykstra B, McKnight KD, McCaffrey L, Hoodless PA, & Eaves CJ.
Identification of a new intrinsically timed developmental checkpoint
that reprograms key hematopoietic stem cell properties. Proc Natl Acad
Sci U S A 104 (14): 5878-82, 2007.
View Abstract
Hou J, Charters AM,
Lee SC, Zhao Y, Wu MK, Jones SJ, Marra MA, & Hoodless PA. A systematic
screen for genes expressed in definitive endoderm by Serial Analysis of
Gene Expression (SAGE). BMC Dev Biol 7: 92, 2007.
View Abstract
Khattra J, Delaney
AD, Zhao Y, Siddiqui A, Asano J, McDonald H, Pandoh P, Dhalla N, Prabhu
AL, Ma K, Lee S, Ally A, Tam A, Sa D, Rogers S, Charest D, Stott J,
Zuyderduyn S, Varhol R, Eaves C, Jones S, Holt R, Hirst M, Hoodless PA,
& Marra MA. Large-scale production of SAGE libraries from microdissected
tissues, flow-sorted cells, and cell lines. Genome Res 17 (1): 108-16,
2007.
View Abstract
McKnight KD, Hou J, &
Hoodless PA. Dynamic expression of thyrotropin-releasing hormone in the
mouse definitive endoderm. Dev Dyn 236 (10): 2909-17, 2007.
View Abstract
Noorali S, Kurita T,
Woolcock B, de Algara TR, Lo M, Paralkar V, Hoodless P, & Vielkind J.
Dynamics of expression of growth differentiation factor 15 in normal and
PIN development in the mouse. Differentiation 75 (4): 325-36, 2007.
View Abstract
Bowie MB,
McKnight KD, Kent DG, McCaffrey L, Hoodless PA, & Eaves CJ.
Hematopoietic stem cells proliferate until after birth and show a
reversible phase-specific engraftment defect. J Clin Invest 116 (10):
2808-16, 2006.
View Abstract
Houde C, Dickinson
RJ, Houtzager VM, Cullum R, Montpetit R, Metzler M, Simpson EM, Roy S,
Hayden MR, Hoodless PA, & Nicholson DW. Hippi is essential for node
cilia assembly and Sonic hedgehog signaling. Dev Biol 300 (2): 523-33,
2006.
View Abstract
Mar L, &
Hoodless PA.
Embryonic fibroblasts from mice lacking Tgif were defective in
cell cycling. Mol Cell Biol 26
(11): 4302-10, 2006.
View Abstract
Siddiqui AS, Khattra
J, Delaney AD, Zhao Y, Astell C, Asano J, Babakaiff R, Barber S, Beland
J, Bohacec S, Brown-John M, Chand S, Charest D, Charters AM, Cullum R,
Dhalla N, Featherstone R, Gerhard DS, Hoffman B, Holt RA, Hou J, Kuo BY,
Lee LL, Lee S, Leung D, Ma K, Matsuo C, Mayo M, McDonald H, Prabhu AL,
Pandoh P, Riggins GJ, de Algara TR, Rupert JL, Smailus D, Stott J, Tsai
M, Varhol R, Vrljicak P, Wong D, Wu MK, Xie YY, Yang G, Zhang I, Hirst
M, Jones SJ, Helgason CD, Simpson EM, Hoodless PA, & Marra MA. A mouse
atlas of gene expression: large-scale digital gene-expression profiles
from precisely defined developing C57BL/6J mouse tissues and cells. Proc
Natl Acad Sci U S A 102 (51): 18485-90, 2005.
View Abstract
Noseda M, McLean G,
Niessen K, Chang L, Pollet I, Montpetit R, Shahidi R, Dorovini-Zis K, Li
L, Beckstead B, Durand RE, Hoodless PA, & Karsan A. Notch activation
results in phenotypic and functional changes consistent with
endothelial-to-mesenchymal transformation. Circ Res 94 (7): 910-7, 2004.
View Abstract
Hoodless
PA, Pye M, Chazaud C, Labbe E, Attisano L, Rossant J, & Wrana JL. FoxH1
(Fast) functions to specify the anterior primitive streak in the mouse.
Genes Dev 15 (10): 1257-71, 2001.
View Abstract
Sirard C, Kim S,
Mirtsos C, Tadich P, Hoodless PA, Itie A, Maxson R, Wrana JL, & Mak TW.
Targeted disruption in murine cells reveals variable requirement for
Smad4 in transforming growth factor beta-related signaling. J Biol Chem
275 (3): 2063-70, 2000.
View Abstract
Tremblay KD,
Hoodless
PA, Bikoff EK, & Robertson EJ. Formation of the definitive endoderm in
mouse is a Smad2-dependent process. Development 127 (14): 3079-90, 2000.
View Abstract
Hoodless PA, Tsukazaki T, Nishimatsu S, Attisano L, Wrana JL, & Thomsen GH.
Dominant-negative Smad2 mutants inhibit activin/Vg1 signaling and
disrupt axis formation in Xenopus. Dev Biol 207 (2): 364-79, 1999.
View Abstract
Hoodless PA, & Wrana
JL. Mechanism and function of signaling by the TGF beta superfamily.
Curr Top Microbiol Immunol 228: 235-72, 1998.
View Abstract
Labbe
E, Silvestri C, Hoodless PA, Wrana JL, & Attisano L. Smad2 and Smad3
positively and negatively regulate TGF beta-dependent transcription
through the forkhead DNA-binding protein FAST2. Mol Cell 2 (1): 109-20,
1998.
View Abstract
Macias-Silva M,
Hoodless PA, Tang SJ, Buchwald M, & Wrana JL. Specific activation of
Smad1 signaling pathways by the BMP7 type I receptor, ALK2. J Biol Chem
273 (40): 25628-36, 1998.
View Abstract
Tang SJ,
Hoodless PA,
Lu Z, Breitman ML, McInnes RR, Wrana JL, & Buchwald M. The Tlx-2
homeobox gene is a downstream target of BMP signalling and is required
for mouse mesoderm development. Development 125 (10): 1877-87, 1998.
View Abstract
Waldrip WR, Bikoff
EK, Hoodless PA, Wrana JL, & Robertson EJ. Smad2 signaling in
extraembryonic tissues determines anterior-posterior polarity of the
early mouse embryo. Cell 92 (6): 797-808, 1998.
View Abstract
Hoodless PA,
Hemmati-Brivanlou A. Inhibitory
control of neural differentiation in mammalian cells.
Development, Genes and Evolution 207:19-28, 1997.
View
Abstract
Li M, Li J,
Hoodless
PA, Tzukazaki T, Wrana JL, Attisano L, & Tsang BK. Mothers against
decapentaplegic-related protein 2 expression in avian granulosa cells is
up-regulated by transforming growth factor beta during ovarian
follicular development. Endocrinology 138 (9): 3659-65, 1997.
View Abstract
Eppert K, Scherer SW,
Ozcelik H, Pirone R, Hoodless P, Kim H, Tsui LC, Bapat B, Gallinger S,
Andrulis IL, Thomsen GH, Wrana JL, & Attisano L. MADR2 maps to 18q21 and
encodes a TGFbeta-regulated MAD-related protein that is functionally
mutated in colorectal carcinoma. Cell 86 (4): 543-52, 1996.
View Abstract
Hoodless PA, Haerry
T, Abdollah S, Stapleton M, O’Connor MB, Attisano L, & Wrana JL. MADR1,
a MAD-related protein that functions in BMP2 signaling pathways. Cell 85
(4): 489-500, 1996.
View Abstract
Macias-Silva M, Abdollah S,
Hoodless PA, Pirone R, Attisano L, & Wrana JL. MADR2 is a
substrate of the TGFbeta receptor and its phosphorylation is required
for nuclear accumulation and signaling. Cell 87 (7): 1215-24, 1996.
View Abstract
Duncan
SA, Manova K, Chen WS, Hoodless P,
Weinstein
DC,
Bachvarova RF, & Darnell JE, Jr. Expression of transcription factor
HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the
developing mouse embryo: HNF-4 is a marker for primary endoderm in the
implanting blastocyst. Proc Natl Acad Sci U S A 91 (16): 7598-602, 1994.
View Abstract
Weinstein
DC,
Ruiz i Altaba A, Chen WS, Hoodless P, Prezioso VR, Jessell TM, & Darnell
JE, Jr. The winged-helix transcription factor HNF-3 beta is required for
notochord development in the mouse embryo. Cell 78 (4): 575-88, 1994. View Abstract
Hoodless PA, Ryan AK,
Schrader TJ, & Deeley RG. Characterization of liver-enriched proteins
binding to a developmentally demethylated site flanking the avian
apoVLDLII gene. DNA Cell Biol 11 (10): 755-65, 1992.
View Abstract
Hoodless PA, Roy RN,
Ryan AK, Hache RJ, Vasa MZ, & Deeley RG. Developmental regulation of
specific protein interactions with an enhancerlike binding site far
upstream from the avian very-low-density apolipoprotein II gene. Mol
Cell Biol 10 (1): 154-64, 1990.
View Abstract
Open Position
We are currently accepting post-doctoral and graduate student
applications
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Mailing Address:
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Terry Fox Laboratory
BC Cancer Agency
675 West 10th
Avenue,
Vancouver BC
Canada V5Z 1L3 |
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Email: |
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hoodless@bccrc.ca |
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Phone Numbers: |
Tel: 604-675-8133
Fax: 604-877-0712
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Terry Fox Laboratory
BC Cancer Agency
675 West 10th
Avenue,
Vancouver BC
Canada V5Z 1L3 |
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