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Research
Interests of Dr. Robert J. Schwartz
Over
the last 20 years, Dr Robert Schwartz has formed a number
of key regulatory paradigms defining regulatory
chemical switches that affect genetic readout. In the late
1970’s, he was the first to elucidate a primary regulatory
paradigm in which non-muscle contractile proteins are down
regulated or switched off during myogenesis and replaced
by muscle specific contractile protein isoforms.
Over
the last
10 years, Dr Robert Schwartz’s fundamental discoveries
were directed toward understanding the critical physical
chemical roles that involve combinatorial and mutual interactions
shared
between the transcription factors, serum response factor,
Nkx2-5, GATA4/6 and Lim proteins in defining the genetic
readout that
underlie the establishment of cardiac and smooth muscle
differentiation.
Dr
Schwartz has shown that SRF, may play a leading role in
the commitment of cardiac progenitors by virtue of its
ability for making specific protein-protein associations
with other
early cardiac enriched transcription factors such as
the cardiac restricted homeodomain factor Nkx2-5, the dual
zinc finger
protein GATA4 and the LIM proteins CRP1 and CRP2.
In
addition,
Dr. Schwartz has also devoted considerable attention
to the chemistry of Nkx2-5, a transcription factor instrumental
in the patterning of the embryonic heart. He showed
that developmental
regulation of the murine Nkx2-5 genetic locus is highly
complex
and modular. Dr Schwartz pinpointed the novel high
affinity Nkx2-5 DNA binding sites and elucidated the regulatory
domains of Nkx2-5 which revealed functional roles in
humans
carrying
Nkx2-5 mutations and displaying congenital atrial septal
defects.
Dr.
Schwartz continues to elucidate the chemical basis underlying
the specification of cardiac muscle cell differentiation,
which will provide opportunities for cell replacement
therapy and
heart regeneration in the future.
Representative Publications
Schwartz, R.J. and Rothblum, K.N. (1981) Gene switching in
myogenesis: differential expression of the chicken actin multigene
family. Biochemistry 20:4122-4129.
Chen, C-Y. and Schwartz, R.J. (1995) Identification of novel
DNA binding targets and regulatory domains of a murine tinman
homeodomain factor, nkx-2.5. J. Biol. Chem. 270:15628-15633.
Chen,
C.Y. and Schwartz, R.J. (1996) Recruitment of tinman homologue,
Nkx-2.5 by serum response factor activates cardiac
-actin gene transcription. Mol. Cell. Biol.,16:6372-6384.
Schwartz, R.J. and Olson, E.N. (1999) Building the heart
piece by piece: modularity of cis-elements regulating
to Nkx2-5 transcription.
Development, 126, 4187-4192.
Chang,D.F, Belaguli,NS,, Roberts,WB., Iyer,D., Wu, S.P., Dong,
X.R.,Marx,J., Moore, MS., Beckerle, M.C., Majesky, M., and.
Schwartz, RJ. (2003) Vascular smooth muscle LIM-only proteins
CRP1 and CRP2 are potent cardiovascular differentiation cofactors.
Dev. Cell 4: 107-118.
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