Our research focuses on exploring novel therapeutic strategies for cancer through a multi-disciplinary approach, including synthetic chemistry, medicinal chemistry, chemical biology, computational biology, and biology. We study gene regulatory pathways including epigenetic proteins, chromatin modification enzymes, and transcription factors. We seek understanding of the biological relevance of these targets in cancer, as well as develop novel therapeutic strategy.
Jun Qi, Ph.D.
360 Longwood Ave. LC2210
Boston, MA 02215
Lab Size: Between 5-10
Our current research focuses on understanding the biological roles of epigenetic proteins, including readers, writers and erasers, in cancer using a combination of chemistry, medicinal chemistry, chemical biology, and biology approaches.
Bromodomains are epigenetic readers that recognize acetyl-lysine mark on histone. We have developed small molecule inhibitors for the bromodomain and extra-terminal (BET) subfamily (BRD2, BRD3, BRD4 and BRDT). With the chemical probe and chemical biology platform we have established, we are now further developing small molecule inhibitors for other bromodomain family members and studying their roles in different types of cancers.
Histone methylation contributes to the regulation of chromatin structure and function, thereby modulating gene expression. Histone methyltransferases are epigenetic writers that manage methylation on different locations. We have been focusing on developing small molecule inhibitors for DOT1L that catalyzes the methylation of H3K79, as well as assay platform to further optimize current probes. We are now developing small molecule inhibitors and tool compounds to study other methyltransferases, including EZH2, PRMT5, and NSD2.
Histone methylation is tightly regulated by methyltransferases and demethylases that mediate the addition and removal of this modification. We are developing small molecule inhibitors and tool compounds for histone lysine demethylases (KDMs) to validate the therapeutic potential of KDM inhibition.
Our team including the scientists who have expertise in chemistry, medicinal chemistry, chemical biology, and biology. We start our effort with designing and developing novel small molecule inhibitors. We use the biology knowledge to guide our design and development of chemistry; then use chemical probes and chemical biology tools to seek novel understanding of the biological relevance of these targets in cancer. Our ultimate goal is to translate our research into human cancer treatment.
Filippakopoulos P*, Qi J.*, Picaud S*, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, Mckeown MR, Wang Y, Christie AL, West N, Cameron MJ, Schwartz B, Heightman TD, La Thangue N, Kung AL, Wiest O, French CA, Knapp S, Bradner JE. Selective inhibition of BET bromodomains. Nature, 2010, 468, 1067-1073. PMCID: PMC3010259
Yi JS*, Federation AJ*, Qi J*, Dhe-Paganon S, Hadler M, Xu X, St Pierre R, Varca AC, Wu L, Marineau JJ, Smith WR, Souza A, Chory EJ, Armstrong SA, Bradner JE. Structure guided DOT1L probe optimization by label-free ligand displacement. ACS Chemical Biology, 2015, 10, 667-674. PMCID: PMC4504433
Zhang H*, Qi J*, Reyes JM, Li L, Rao PK, Li F, Lin CY, Perry JA, Lawlor MA, Federation A, De Raedt T, Li Y, Duarte MA, Zhang Y, Herter-Sprie GS, Kikuchi E, Carretero J, Perou CM, Reibel JB, Paulk J, Bronson RT, Watanabe H, Fillmore CM, Kim CF, Hammerman PS, Brown M, Cichowski K, Long H, Bradner JE, Wong KK. Oncogenic deregulation of EZH2 as an opportunity for targeted therapy in lung cancer. Cancer Discovery, 2016, -6, 1006-1021. PMCID: PMC5010480
Hideshima T*, Qi J*, Paranal RM*, Tang W, Greenberg E, West N, Colling ME, Estiu G, Mazitschek R, Perry JA, Ohguchi H, Cottini F, Minura N, Gorgun G, Tai YT, Richardson RD, Wiest O, Schreiber SL, Anderson KC, Bradner JE. Discovery of selective small molecule HDAC6 inhibitor for overcoming proteasome inhibitor resistance in multiple myeloma. Proc Natl Acad Sci USA, 2016, 113, 13162-13167. PMCID: PMC5135369
Roti G*, Qi J*, Kitara S, Sanchez-Martin M, Saur Conway A, Varca AC, Wu L, Kung AL, Ferrando AA, Bradner JE, Stegmaier K. Leukemia-specific delivery mutant NOTCH1 targeted therapy. The Journal of Experimental Medicine. 2018, 215, 197-216.
* Link to all publications