Irfan A Asangani, Ph.D.

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Assistant Professor of Cancer Biology
Department: Cancer Biology
Graduate Group Affiliations

Contact information
421 Curie Blvd
611 BRB II/III
Philadelphia, PA 19104-6160
Office: 215-746-8780
Lab: 215-746-8781
Education:
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.
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Description of Research Expertise

Research Interest:
Our lab investigates the molecular epigenetic events associated with cancer

Key words:
Cancer epigenetics, Chromatin regulation, Histone methyltransferase, transcription, non-coding RNA, Targeted therapy, Drug resistance

Lab Members:

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 Publications

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

Stypulkowski E., Asangani I.A., Witze E: APT1 directs the asymmetric partitioning of Notch and Wnt signaling during cell division. Sci. Signaling 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 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.

Gollavilli PN, Pawar A, Wilder-Romans K, Engelke C, Dommeti VL, Krishnamurthy PM, Nallasivam A, Apel IA, Xu T, Qin ZS, Feng FY, Asangani IA: BET Bromodomain proteins are essential for the oncogenic EWS-fusion driven Ewing Sarcoma. AACR, Washington, DC April 2017.

Steven Kregel, Rohit Malik, Irfan A. Asangani, Kari Wilder-Romans, Xia Jiang, Ingrid J. Apel, Gautham Ravi, Jean Tien, Xuhong Cao, Felix Y. Feng, Corey Speers, Shaomeng Wang, Arul M. Chinnaiyan: Functional and mechanistic interrogation of BET bromodomain de-graders for the treatment of metastatic castration resistant prostate cancer. AACR, Washington, DC April 2017.

Asangani I.A., Wilder-Romans K., Dommeti V.L., Krishnamurthy P.M., Apel I.J., Escara-Wilke J., Plymate S.R., Navone N.M., Wang S., Feng F.Y., Chinnaiyan A.M.: BET Bromodomain Inhibitors Enhance Efficacy and Disrupt Resistance to AR Antagonists in the Treatment of Prostate Cancer. Mol Cancer Res 0472.2015: Epub ahead of print, Jan 2016.

Mody RJ, Wu YM, Lonigro RJ, Cao X, Roychowdhury S, Vats P, Frank KM, Prensner JR, Asangani I, Palanisamy N, Dillman JR, Rabah RM, Kunju LP, Everett J, Raymond VM, Ning Y, Su F, Wang R, Stoffel EM, Innis JW, Roberts JS, Robertson PL, Yanik G, Chamdin A, Connelly JA, Choi S, Harris AC, Kitko C, Rao RJ, Levine JE, Castle VP, Hutchinson RJ, Talpaz M, Robinson DR, Chinnaiyan AM.: Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth. JAMA 314(9):913-25., Sep 2015

Scanlon CS, Banerjee R, Inglehart RC, Liu M, Russo N, Hariharan A, van Tubergen EA, Corson SL, Asangani IA, Mistretta CM, Chinnaiyan AM, D'Silva NJ: Galanin modulates the neural niche to favour perineural invasion in head and neck cancer. Nature Communications 6: 6885, Apr 2015.

Malik R, Khan AP, Asangani IA, Cieślik M, Prensner JR, Wang X, Iyer MK, Jiang X, Borkin D, Escara-Wilke J, Stender R, Wu Y-M, Niknafs YS, Jing Xi, Qiao Y, Palanisamy N, Kunju LP, Krishnamurthy PM, Yocum AK, Mellacheruvu D, Nesvizhskii AI, Cao X, Dhanasekaran SM, Feng FY, Grembecka J, Cierpicki T, Chinnaiyan AM: Targeting the MLL complex in castration-resistant prostate cancer. Nature Medicine 21(4): 344-52, Apr 2015.

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Last updated: 12/04/2018
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