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.
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.