Dr. Sichun Yang started his biophysical research at the University of California San Diego after receiving B.S. and M.S. in Physics from China. He obtained a Ph.D. in Biophysics from UCSD on September 9th, 2006. His PhD research with Dr. Herbert Levine and Dr. Jose Onuchic (both now at Rice) focused on protein folding and protein-protein assembly, from the perspective of computer simulation and statistical mechanics. In 2006-2010, Dr. Yang carried out his postdoctoral research with Dr. Benoit Roux at the Department of Biochemistry and Molecular Biology at the University of Chicago. He began to bridge computation and experiment and demonstrated that combining computer simulation and synchrotron X-ray scattering is ideally positioned to study the structural dynamics of bimolecular complexes (PNAS, 2010). This work has been featured in a News & Views article (Nature, 2010).
In collaboration with Dr. Geof Greene at UChicago, Dr. Yang began to work on the molecular biophysics of estrogen receptor (ER), a key molecule in breast cancer biology, and has received a prestigious idea award from the Department of Defense. Dr. Yang joined the School of Medicine at Case Western Reserve University in 2010
The research in the Yang laboratory is focused on the structure, dynamics, and function of nuclear estrogen receptors (ER) regulating the development of early-stage breast cancers. Methods used in the lab include computational techniques (molecular dynamics simulation and residue-based structural modeling), experimental biophysical techniques (small-angle x-ray solution scattering or SAXS and labeling tools), and more importantly, their judicious combination. Our studies benefit from the excellent computing facilities and synchrotron sources to which we have access, and close links with other laboratories here at Cleveland and other parts of the nation.
Current efforts in the Yang lab include:
Nuclear estrogen receptor (ER): Structure and function
A typical American woman has about a 12% chance of developing breast cancer in her lifetime. However, the current breast cancer adjuvant therapy that targets the estrogen receptor (ER) has undesirable side effects. What remain unresolved are the molecular mechanisms by which ER structural assemblies modulate internal signaling in the development of ER-positive breast cancer. We aim to determine the molecular basis of ER allosteric communication in the regulation of down-stream signal transductions, which should lead to novel therapeutic approaches to targeting ER-positive breast cancers.
Integrated methods for macromolecular complex assembly
An emerging challenge in structural biology is to resolve the dynamics and structure of multimeric assemblies of biomolecular complexes such as multidomain proteins. The difficulty arises from their intrinsic flexibility and conformational multiplicity due to multiple moving parts or domains. We are actively building a new theoretical and experimental program that integrates molecular models and simulations and small-angle x-ray solution scattering (SAXS) techniques. The newly developed approach (now called BSS-SAXS method) allows us to achieve molecular insights into macromolecular assembly mechanisms in general. Our current efforts include the continued development of the BSS-SAXS method for investigating macromolecular assemblies.