Irfan A Asangani, Ph.D.
611 BRB II/III
Philadelphia, PA 19104-6160
B.S. (Biochemistry (First Class) )
Madras University (India), 1999.
M.S. (Biochemistry (First Class) )
Madras University (India), 2001.
Ph.D. (Cancer Biology (Summa cum laude))
Klinikum Mannheim / DKFZ / Heidelberg University (Germany) Laboratory of Heike Allgayer, M.D., Ph.D., 2009.
Description of Research ExpertiseResearch Interest:
Our lab investigates the molecular epigenetic events associated with cancer
Cancer epigenetics, Chromatin regulation, Histone methyltransferase, transcription, non-coding RNA, Targeted therapy, Drug resistance
Rotation Projects: Rotation projects are available in each of the main areas of the lab.Please contact Dr. Asangani for details.
Description of Research:
Cancer cells display an altered landscape of chromatin leading to broad changes in the gene expression. In addition, genes involved in chromatin remodeling and epigenetic regulation are frequently and specifically mutated in a wide variety of cancers including prostate cancer. While known to serve important roles in the control of gene expression and development, these largely unexpected mutation findings have illuminated newly recognized mechanisms central to the genesis of cancer. Gaining insight into the mechanism of chromatin regulation in cancer will offer the potential to reveal novel approaches and targets for effective therapeutic intervention.
Our laboratory employs a multidisciplinary approach to study these molecular epigenetic events associated with cancer towards the overarching goal of translating this knowledge into clinical tools by developing novel diagnostic, prognostic and therapeutic strategies. Additionally, we investigate the mechanisms of resistance to targeted therapies and develop novel combinatorial approaches that act on compensatory/new pathways in resistant tumors. Our basic strategy is to develop and deploy rational polytherapy upfront that suppresses the survival and emergence of resistant tumor cells.
Current Research: Prostate cancer is the most common non-cutaneous malignancy and second leading cause of cancer-related mortality in men of the Western world. While effective surgical, radiation, and androgen ablation therapy exists for clinically localized prostate cancer, progression to metastatic castration-resistant prostate cancer (CRPC) remains essentially incurable. Despite the success of recently approved therapies targeting AR (androgen receptor) signaling, durable responses are limited due to acquired resistance. Therefore, the identification and therapeutic targeting of co-activators or mediators of AR transcriptional signaling should be considered as alternate strategies to treat CRPC. Our research is focused on chromatin modifying enzymes and chromatin-associated epigenetic regulator proteins in the context of prostate cancer initiation and progression to metastasis.
Current areas of interest within the laboratory include:
1. Delineating the role of chromatin regulators, and its importance in AR mediated transcription
2. Understanding the role of non-coding RNA in regulating higher order chromatin structure
3. Investigate the molecular mechanisms of resistance to targeted therapies
Selected PublicationsRasool RU, Natesan R, Deng Q, Aras S, Lal P, Sander Effron S, Mitchell-Velasquez E, Posimo JM, Carskadon S, Baca SC, Pomerantz MM, Siddiqui J, Schwartz LE, Lee DJ, Palanisamy N, Narla G, Den RB, Freedman ML, Brady DC, Asangani IA.: CDK7 inhibition suppresses Castration-Resistant Prostate Cancer through MED1 inactivation. Cancer Discovery Aug 2019 Notes: doi: 10.1158/2159-8290 CD-19-0189. [Epub ahead of print]
Kregel S, Malik R, Asangani IA, Wilder-Romans K, Rajendiran T, Xiao L, Vo JN, Soni T, Cieslik M, Fernadez-Salas E, Zhou B, Cao X, Speers C, Wang S, Chinnaiyan AM.: Functional and Mechanistic Interrogation of BET Bromodomain Degraders for the Treatment of Metastatic Castration-resistant Prostate Cancer. Clin Cancer Res. 25(13): 4038-4048, Jul 1 2019 Notes: doi: 10.1158/1078-0432.CCR-18-3776. Epub 2019 Mar 27.
Siddiqui A, Gollavilli PN, Schwab A, Vazakidou ME, Ersan PG, Ramakrishnan M, Pluim D, Coggins S, Saatci O, Annaratone L, Hm Schellens J, Kim B, Asangani IA, Rasheed SAK, Marchiò C, Sahin O, Ceppi P.: Thymidylate synthase maintains the de-differentiated state of triple negative breast cancers. Cell Death Differ Feb 2019 Notes: doi: 10.1038/s41418-019-0289-6. [Epub ahead of print]
Pawar A., Gollavilli P.N, Wang S., Asangani I.A: Resistance to BET inhibitor leads to alternative therapeutic vulnerabilities in castration-resistant prostate cancer. Cell Reports 27;22(9):2236-2245, Feb 2018
Gollavilli PN, Pawar A, Wilder-Romans K, Natesan R, Engelke CG, Dommeti VL, Krishnamurthy PM, Nallasivam A, Apel IJ, Xu T, Qin ZS, Feng FY, Asangani IA: EWS/ETS-Driven Ewing Sarcoma Requires BET Bromodomain Proteins. Cancer Res 78(16): 4760-4773, Aug 2018 Notes: doi: 10.1158/0008-5472.CAN-18-0484. Epub 2018 Jun 13.
Gollavilli P.N., Pawar A., Wang S., Wilder-Romans K., Ramakrishnan N., Engelke C.G., Dommeti V.L., Krishnamurthy P.M., Nallasivam A., Apel I.J., Xu T., Qin Z.S., Feng F.Y., Asangani I.A.: EWS/ETS-driven Ewing Sarcoma requires BET bromodomain proteins. Cancer Res June 2018 Notes: Epub 2018 Jun 13, DOI: 10.1158/0008-5472.CAN-18-0484.
Aishwarya S Pawar, Irfan A Asangani: Resistance to BET inhibitor leads to new therapeutic vulnerabilities in castration resistant prostate cancer. AACR, Washington, DC April 2018 Notes: poster.
Stypulkowski E., Asangani I.A., Witze E: APT1 directs the asymmetric partitioning of Notch and Wnt signaling during cell division. Sci. Signaling DOI: 10.1126/scisignal.aam8705, January 2018.
Chakravarthi B.V.S.K., Chandrashekar D.S, Agarwal S., Balasubramanya S.A.H., Pathi S.S., Goswami M.T., Jing X., Wang R., Mehra R., Asangani I.A., Chinnaiyan A.M., Manne U., Sonpavde G., Netto G.J., Gordetsky J., Varambally S. : miR-34a Regulates Expression of the Stathmin-1 Oncoprotein and Prostate Cancer Progression. Mol Cancer Res Page: DOI:10.1158/1541-7786.MCR-17-0230, October 2017.
Wang X, Qiao Y., Asangani I.A., Ateeq B, Poliakov A., Cieślik M., Pitchiaya S., Chakravarthi B.V., Cao X., Jing X., Wang C.X., Apel I.J., Wang R., Tien J.C., Juckette K.M., Yan W., Jiang H., Wang S., Varambally S., Chinnaiyan A.M.: Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer. Cancer Cell pii: S1535-6108(17)30060-0, June 2017 Notes: doi: 10.1016/j.ccell.2017.02.017.