Sichun Yang, PhD

Professor
Department of Nutrition
School of Medicine
Professor
Center for Proteomics and Bioinformatics
School of Medicine
Professor
Department of Pharmacology
School of Medicine
Professor
Department of Physiology and Biophysics
School of Medicine
Member
Molecular Oncology Program
Case Comprehensive Cancer Center

Dr. Sichun Yang is a tenured Professor at Case Western Reserve University School of Medicine and a member of the Case Comprehensive Cancer Center since 2010. He earned his PhD in Biophysics from the University of California San Diego and completed postdoctoral training in Biochemistry and Molecular Biology at the University of Chicago.

Dr. Yang's research addresses developing better therapeutics for ER+ breast cancer, which represents 70% of breast cancer cases. His laboratory investigates the structure-function relationships of the Estrogen Receptor, with particular focus on intrinsic disorder, cross-domain allostery, and targeted small-molecule discovery.

Through an integrated approach combining biophysics, structural biology, cell-based assays, and computational modeling, Dr. Yang has developed small-molecule discovery platforms that target previously inaccessible regions of the estrogen receptor. These platforms enable the identification of selective small-molecule inhibitors with distinct mechanisms of action, addressing current therapeutic limitations.

Dr. Yang's research has identified "molecular switches" that control estrogen receptor signaling. This work translates cancer biology discoveries into next-generation ER+ breast cancer therapeutics with improved on-target selectivity.

Teaching Information

Courses Taught

PHRM 528. Contemporary Approaches to Drug Discovery

Research Information

Research Projects

Publications

Selected Publications

  1. Du Z, Wang H, Luo S, Yun Z, Wu C, Yang W, Buck M, Zheng W, Hansen AL, Kao HK, and Yang S. "The sequence-structure-function relationship of intrinsic ERα disorder," Nature, 638, 1130–1138 (2025); https://pubmed.ncbi.nlm.nih.gov/39779860
  2. Wang H, Luo Y, Artham S, Wang Q, Peng Y, Yun Z, Li X, Wu C, Liu Z, Weber-Bonk KL, Pai CP, Cao Y, Yue J, Park S, Keri RA, Geng L, McDonnell DP, Kao HY, and Yang S. “Mitoxantrone inhibits and downregulates ERα through binding at the DBD-LBD interface,” bioRxiv, doi: 10.1101/2025.01.07.631371 (2025); https://pubmed.ncbi.nlm.nih.gov/39829897
  3. Yang S and Bernado P. "Integrative Biophysics: protein interaction and disorder," Journal of Molecular Biology, 432 (9) 2843-2845 (2020); https://pubmed.ncbi.nlm.nih.gov/32247763
  4. Huang W, Peng Y, Kiselar J, Zhao X, Albaqami A, Mendez D, Chen Y-H, Chakravarthy S, Gupta S, Ralston C, Kao H-Y, Chance MR, and Yang S. "Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains," Nature Communications, 9 (1) 3520 (2018); https://pubmed.ncbi.nlm.nih.gov/30166540
  5. Yang S. "Methods for SAXS-based structure determination of biomolecular complexes," Advanced Materials, 26 (46) 7902–7910 (2014); https://pubmed.ncbi.nlm.nih.gov/24888261