I have spent the 5 years working in Dr. Frank Conlon's
lab at UNC-CH. Our lab is interested in understanding the molecular
mechanisms of early heart specification and development. Understanding
the mechanisms by which heart development occurs is an immensely
important pursuit for modern developmental biology and medicine,
especially when one considers that about one out of every hundred
live births exhibit congenital heart defects. My initial rotation
project was to clone a novel gene, Tbx20, from the African
Clawed Frog (Xenopus laevis). Tbx20 is a transcription
factor that is likely involved in controlling cardiac development.
After cloning Tbx20 I first had to characterize its expression
pattern in the early frog embryo. By using whole-mount in situ
hybridization techniques (which serve to stain an embryo blue
wherever the gene being studied is turned on) I showed that Tbx20
is expressed throughout all of the heart-forming regions over
the entire course of heart development.
Tbx20 Expression in Xenopus
laevis
Click on image for larger version
Anterior view of a stage 16 embryo. Dorsal side is facing
up.
Expression in heart primordia and cement gland
Ventral view of the
anterior portion of a stage 27 embryo.
Expression in heart primordia and cement gland
Lateral view of the anterior portion of a stage 35 embryo.
Expression in heart , hindbrain, and cement gland
Ventral view of the posterior portion of a stage 27 embryo
By analyzing the DNA sequence of Tbx20 I then demonstrated
that it is very closely related to Tbx20 genes in organisms
ranging from chickens, frogs, and fish to mice and humans. This
information further suggested that Tbx20 is likely involved
in controlling the creation of a heart not only in frogs but also
in all vertebrates, including humans. I then spent some time working
the collected data into a manuscript, which has since been published
in the journal Development, Genes and Evolution. I am now using
various techniques to perturb the normal expression of Tbx20
in the frog to begin to elucidate the role this gene may be playing
in the development of this most vital of organs.
I have further gone on to investigate the cellular and molecular
relationship between two T-box genes, Tbx5 and Tbx20.
I have demonstrated that blocking Tbx5 or Tbx20
gives phenotypes that display a high degree of similarity as judged
by overall gross morphology, molecular marker analysis, and cardiac
physiology, implying that the two genes are required for and have
non-redundant functions in early heart development. In addition,
I have demonstrated that although coexpressed, Tbx5 and
Tbx20 are not dependent on one another's expression, but
rather have a synergistic role during early heart development.
Consistent with this proposal, I have shown that TBX5 and TBX20
can physically interact, mapped the interaction domains, shown
a cellular interaction for the two proteins in cardiac development
and therefore, provided the first evidence for direct interaction
between members of the T-box gene family.
Brown D. D.,
Binder O., Pagratis M., Parr B.A., Conlon F.L.Developmental
expression of the Xenopus laevis Tbx20 orthologue. Dev
Genes Evol. 2003 Jan; 212(12): 604-7. (PDF
version)
Brown, D. D., Martz, S. N., Binder, O.,
Goetz, S. C., Price, B. M. J., Smith, J. C. and Conlon, F. L.
(2005). Tbx5 and Tbx20 act synergistically to control
vertebrate heart morphogenesis. Development 132, 553-563.
(PDF version - Recommended
read by Faculty of 1000 Biology)
Brown, D.D., Davis, A.C., Conlon, F.L.,
(2005) Xtn3 is a developmentally expressed cardiac and
skeletal muscle-specific novex-3 titin isoform. Gene Expression
Patterns (in press) (PDF)
Goetz, S.C., Brown, D.D., Conlon, F.L., (2006) TBX5 is
required for embryonic cardiac cell cycle progression. Development
133: 2575-2584. (PDF)
Feduccia, A. and Nowicki, J. (2002). The hand of birds revealed
by early ostrich embryos. Naturwissenschaften 89, 391-3. (I took
a picture for the article which was used as the cover for the
journal)
Honors/Awards
UNC Lineberger Graduate Fellow Award, 2006
UNC Graduate School Dissertation Completion Fellowship, 2006-present
National Science Foundation Graduate Research Fellowship, 2002-2005
Best Presentation, UNC Genetics/Duke Cell Biology Retreat, Wilmington,
NC, 2004
Best Student Presentation Award, UNC Cellular and Molecular Biology
(CMB) Annual Retreat, 2003
Spessard Award in Biology (Highest Biology Honor), Hendrix College,
2000
Chairman's Scholarship (Academic Scholarship), Hendrix College,
1996-2000
Conferences
"The Requirement for Tbx20 in Vertebrate Heart Morphogenesis".
UNC Cellular and Molecular Biology (CMB) Annual Retreat, 4-28-2003
"Tbx5 and Tbx20 act synergistically to control
vertebrate heart morphogenesis". UNC Genetics/Duke Cell Biology
Retreat, Wilmington, NC, 9-17-2004
"Tbx5 and Tbx20 act synergistically to control
vertebrate heart morphogenesis". 13th International Conference
of the International Society of Differentiation (ISD), Honolulu,
Hawaii, USA, 9-5-2004
"Estimated Kernel Home Ranges, Seasonal Movements, and
Habitat Uses of the Timber Rattlesnake". National Conference
for Undergraduate Research (NCUR) in Missoula, Montana, April
27, 2000 and at the Arkansas Academy of Sciences, Little Rock,
Arkansas April 7-8, 2000
Education
Doctorate of Philosophy, Biology, Expected December 2006
University of North Carolina at Chapel Hill, Chapel Hill, NC
Dissertation: Characterization of the role of Tbx20 in vertebrate
heart development
Graduate Advisor: Dr. Frank L. Conlon
Bachelor of Arts, Biology; May 2000
Distinction in Biology
Hendrix College, Conway, AR
Positions
Pre-Doctoral Fellow/Ph.D. Research, Department of Biology, University
of North Carolina at Chapel Hill, Chapel Hill, NC,
August 2001 - present
Research Technologist, Division of Toxicology, University of
Arkansas for Medical Sciences (UAMS), Little Rock, AR
April 2000 - June 2001
-Studied the role of gamma-aminobutyric acid receptor type A (GABAA-R)
subunits in the rat kidney.
Field Researcher, Department of Biological Sciences, University
of Arkansas, Fayetteville, AR
June 1999 - September 1999
-Tracked the seasonal movement patterns and habitat uses of the
Timber Rattlesnake (Crotalus horridus horridus) using radio-telemetry
Research Technician, Department of Physiology, University of
Arkansas for Medical Sciences (UAMS), Little Rock, AR
June 1998 - September 1998
-Studied the rates of influx and efflux through the Na+/K+ pump
and the K+/Cl- co-transporter of rabbit erythrocytes using Rubidium-86.
Teaching Experience
Laboratory Assistant, Department of Biology, Hendrix College,
Conway, AR
September 1998 - May 2000
-Assisted undergraduates in General Zoology, General Physiology,
and General Ecology labs
Teaching Assistant, Department of Biology, University of North
Carolina at Chapel Hill, Chapel Hill, NC,
January 2002 - May 2002
-Held recitations twice a week and hosted exam review sessions
for Cell and Developmental Biology course
Random
stuff I've done while goofing off in the lab (a.k.a. downtime)
My first ever Flash animation (done 5 years ago). Pretty bad.
