DEPARTMENT OF CHEMISTRY

Affiliations

Chemistry of Life Processes Institute (CLP)

Interdisciplinary Biological Sciences Graduate Program (IBiS)

International Institute for Nanotechnology (IIN)

Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine

Center for Human Immunobiology, Feinberg School of Medicine

Research Statement

Our research group is dedicated to the exploration of innovative small molecule and biologic based therapeutic approaches that function beyond traditional inhibitors and antagonists. We are committed to targeting disease-causing proteins that were previously considered undruggable, opening up new possibilities for treating a wide range of human diseases. By combining various disciplines such as omics technologies (proteomics, functional genomics, and chemical genetics), chemical biology, and organic synthesis, our interdisciplinary research program focuses on three primary areas: 1) cancer neoantigen modulators for innovative cancer immunotherapy; 2) selective cancer therapy by identifying cancer-specific vulnerabilities; 3) small molecule degraders targeting not-yet-druggable oncogenic proteins.

Selected Publications

Kramer LT and Zhang X. Expanding the landscape of E3 ligases for targeted protein degradation. Curr. Res. Chem. Biol., 2 (2022) 1-5.

Tao Y†, Remillard D, Vinogradova EV, Yokoyama M, Banchenko S, Schwefel D, Melillo B, Schreiber SL, Zhang X† and Cravatt BF†. Targeted Protein Degradation by Electrophilic PROTACs that Stereoselectively and Site-Specifically Engage DCAF1. J. Am. Chem. Soc. 14 (2022) 18688-18699. (†co-corresponding authors)

Zhang X, Luukkonen LM, Eissler CL, Crowley VM, Yamashita Y, Schafroth MA, Kikuchi S, Weinstein DS, Symons KT, Nordin BE, Rodriguez JL, Wucherpfennig TG, Bauer L, Dix MM, Stamos D, Kinsella TM, Simon GM, Baltgalvis KA and Cravatt BF. DCAF11 supports targeted protein degradation by electrophilic proteolysis-targeting chimeras. J. Am. Chem. Soc., 143 (2021) 5141-5149.

Zhang X, Thielert M, Li H and Cravatt BF. SPIN4 is a principal endogenous substrate of the E3 ubiquitin ligase DCAF16. Biochemistry. 60 (2021) 637-642.

Zhang X, Crowley VM, Wucherpfennig TG, Dix MM, Cravatt BF. Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16. Nat. Chem. Biol., 15 (2019) 737-746.

Zhang X. Chemical Proteomics for Expanding the Druggability of Human Disease. ChemBioChem, 21 (2020) 1-3.

Vinogradova EV, Zhang X, Remillard D, Lazar DC, Suciu RM, Wang Y, Bianco G, Yamashita Y, Crowley VM, Schafroth MA, Yokoyama M, Konrad DB, Lum KM, Simon GM, Kemper EK, Lazear MR, Yin S, Blewett MM, Dix MM, Nguyen N, Shokhirev MN, Chin EN, Lairson LL, Melillo B, Schreiber SL, Forli S, Teijaro JR, Cravatt BF. An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human Immune Cells. Cell, 182 (2020) 1-18.

Zhang X, Cao J, Miller SP, Jing H, Lin H. Comparative nucleotide-dependent interactome analysis reveals shared and differential properties of KRas4a and KRas4b. ACS Cent. Sci., 4 (2018) 71-80.

Zhang X, Spiegelman NA, Nelson OD, Jing H, Lin H. SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation. eLife, 6 (2017) e25158.

Zhang X, Khan S, Jiang H, Antonyak MA, Chen X, Spiegelman NA, Shrimp JH, Cerione RA, Lin H. Identifying the functional contribution of the defatty-acylase activity of SIRT6. Nat. Chem. Biol., 12 (2016) 614-620.

Jing H*, Zhang X*, Wisner SA, Chen X, Spiegelman NA, Linder ME, Lin H. SIRT2 and lysine fatty acylation regulate the oncogenic activity of K-Ras4a. eLife, 6 (2017) e32436. (*equal contribution)

Jiang H*, Zhang X*, Lin H. Lysine fatty acylation promotes lysosomal targeting of TNF-α. Sci. Rep., 6 (2016) 24371. (*equal contribution)

He B*, Hu J*, Zhang X*, Lin H. Thiomyristoyl peptides as cell-permeable Sirt6 inhibitors. Org. Biomol. Chem., 12 (2014) 7498-7502. (*equal contribution)

Zhang X, Song Z, Xu J, Ma Z. Improving the NQO1-Inducing Activities of Phenolic Acids from Radix Salvia miltiorrhiza: a Methylation Strategy. Chem. Biol. Drug Des., 78 (2011) 558-566.

Zhang X, Luo L, Ma Z. A deuterium-labelling mass spectrometry–tandem diode-array detector screening method for rapid discovery of naturally occurring electrophiles. Anal. Bioanal. Chem., 400 (2011) 3463-3471.

Zhang X, Ma Z. Characterization of bioactive thiophenes from the dichloromethane extract of Echinops grijisii as Michael addition acceptors. Anal. Bioanal. Chem., 397 (2010) 1975-1984.

Zhang X, Zhao X, Ma Z. PYDDT, a novel phase 2 enzymes inducer, activates Keap1-Nrf2 pathway via depleting the cellular level of glutathione. Toxicol. Lett., 199 (2010) 93-101.

Zhang X, Ma Z. A new fluorescein isothiocyanate-based screening method for the rapid discovery of electrophilic compounds. Anal. Methods, 2 (2010) 1472-1478.

Selected Honors/Awards

• Liz and Eric Lefkofsky Innovation Research Award, 2023
• Falk Medical Research Trust Catalyst Award, 2022
• CLP Cornew Innovation Award, 2022
• Ono Pharma Breakthrough Science Initiative Award, 2022
• Damon Runyon-Dale F. Frey Award for Breakthrough Scientists, 2022
• Illumina Pilot Award, 2022
• NCI-SPORE in Prostate Cancer Career Enhancement Program Award, 2022
• The NIH Pathway to Independence Award, 2020
• Keystone Symposia Future of Science Fund Scholarship, 2020
• Damon Runyon Postdoctoral Fellowship Award, 2018
• Chinese Government Award for Outstanding Students Abroad, 2018
• Bayer Teaching Excellence Award of Cornell University, 2013
• Eli Lilly Asia Outstanding Graduate Thesis Award, 2011
• Chu Kochen Scholarship of Zhejiang University, 2010