Our research investigates topics at the interface of chemistry and biology, focusing on elucidating the molecular basis of cellular pathways important for human health and disease biology. We employ integrative approaches to study the structure and behavior of macromolecules, understand their functions, and then predict and validate their roles in different cellular contexts. Current research areas include selective autophagy, chromatin biology and epigenetics, and biomolecular condensates.
Dr. Zhang’s research investigates topics at the interface of chemistry and biology, focusing on elucidating the molecular basis of cellular pathways important for human health and disease biology. We employ integrative approaches to study the structure and behavior of macromolecules, understand their functions, and then predict and validate their roles in different cellular contexts.
Current research projects include:
1. Selective autophagy. Research in the lab aims to understand the mechanism and regulation of SQSTM1/p62, a stress-induced multifunctional master regulator. p62 mediates many key cellular responses such as nutrient sensing and inflammation, and is commonly deregulated in cancer and neurodegenerative diseases. This knowledge could lead to new approaches in combination cancer therapy.
2. Biological condensates. We recently made the interesting observation that many proteins form condensates in cells. Our current research investigates the content, regulation, and functional significance of these membrane-less organelles in vitro and in cells. The goal is to develop a comprehensive view of how cells control condensates formation/disassembly and how condensates regulate biological reactions.
3. Chromatin biology and epigenetics. We have broad interests in the structure-function relationship of chromatin-related proteins and how epigenetic marks regulate nuclear processes. We hope to apply this knowledge in drug development for personalized medicine eventually.
- Zhang Y, Narlikar GJ, and Kutateladze TG.
"Enzymatic reactions inside biological condensates."
J Mol Biol 433, 166624 (2021). (invited review)
- Zhang Y, Guo Y, Gough SM, Zhang J, Vann KR, Li K, Cai L, Shi X, Aplan PD, Wang GG, Kutateladze TG.
"Mechanistic insights into chromatin targeting by leukemic NUP98-PHF23 fusion."
Nat Commun 11, 3339 (2020).
- Zhang Y, Bertulat B, Tencer AH, Ren X, Wright GM, Black J, Cardoso MC, Kutateladze TG.
"MORC3 Forms Nuclear Condensates through Phase Separation."
iScience 17, 182 (2019).
- Zhang Y, Jang Y, Lee JE, Ahn JW, Xu L, Holden MR, Cornett EM, Krajewski K, Klein BJ, Wang SP, Dou Y, Roeder RG, Strahl BD, Rothbart SB, Shi X, Ge K, Kutateladze TG.
"Selective binding of the PHD6 finger of MLL4 to histone H4K16ac links MLL4 and MOF."
Nat Commun 10, 2314 (2019).
- Zhang Y, Klein BJ, Cox KL, Bertulat B, Tencer AH, Holden MR, Wright GM, Black J, Cardoso MC, Poirier MG, Kutateladze TG. "Mechanism for autoinhibition and activation of the MORC3 ATPase."
Proc Natl Acad Sci U S A 116, 6111 (2019).
- Zhang Y, Mi W, Xue Y, Shi X, Kutateladze TG.
"The ZZ domain as a new epigenetic reader and a degradation signal sensor."
Crit Rev Biochem Mol Biol 54, 1 (2019). (Review)
- Zhang Y, Mun SR, Linares JF, Ahn J, Towers CG, Ji CH, Fitzwalter BE, Holden MR, Mi W, Shi X, Moscat J, Thorburn A, Diaz-Meco MT, Kwon YT, Kutateladze TG.
"ZZ-dependent regulation of p62/SQSTM1 in autophagy."
Nat Commun 9, 4373 (2018).
- Mi W, Zhang Y, Lyu J, Wang X, Tong Q, Peng D, Xue Y, Tencer AH, Wen H, Li W, Kutateladze TG, Shi X.
"The ZZ-type zinc finger of ZZZ3 modulates the ATAC complex-mediated histone acetylation and gene activation."
Nat Commun 9, 3759 (2018).
- Zhang Y, Xue Y, Shi J, Ahn J, Mi W, Ali M, Wang X, Klein BJ, Wen H, Li W, Shi X, Kutateladze TG.
"The ZZ domain of p300 mediates specificity of the adjacent HAT domain for histone H3."
Nat Struct Mol Biol 25, 841 (2018).