Irfan A Asangani, Ph.D.
Assistant Professor of Cancer Biology
Department: Cancer Biology
Graduate Group Affiliations
Contact information
421 Curie Blvd
611 BRB II/III
Philadelphia, PA 19104-6160
611 BRB II/III
Philadelphia, PA 19104-6160
Office: 215-746-8780
Lab: 215-746-8781
Lab: 215-746-8781
Email:
asangani@upenn.edu
asangani@upenn.edu
Publications
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), 2009.
Permanent linkB.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), 2009.
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
Rasool RU, Natesan R, Asangani IA: Toppling the HAT to treat lethal prostate cancer Cancer Discovery 11(5): 1011-1013, May 2021 Notes: doi: 10.1158/2159-8290.CD-21-0184.Gollavilli PN, Parma B, Siddiqui MA, Yang H, Ramesh V, Napoli F, Schwab A, Natesan R, Asangani IA, Brabletz T, Pilarsky C, Ceppi P: Exploration of endogenous miRNA-200b/c activity and regulation through a functional dual fluorescence reporter. Oncogene 40(12): 2309-2322, March 2021.
Deng Q, Rasool RU, Russell RM, Natsan R, Asangani IA: Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19. iScience. iScience, 24(3): 102254, March 2021.
Asangani IA, Blair IA, Van Duyne G, Hilser VJ, Moiseenkova-Bell V, Plymate S, Sprenger C, Wand AJ, Penning TM: Using biochemistry and biophysics to extinguish androgen receptor signaling in prostate cancer. Journal of Biological Chemistry 296: 100240, January 2021.
Siddiqui MA, Gollavilli PN, Ramesh V, Parma B, Schwab A, Vazakidou ME, Natesan R, Saatci O, Rapa I, Bironzo P, Schuhwerk H, Asangani IA, Sahin O, Volante M, Ceppi P : Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer. British Journal of Cancer 124(1): 281-289, January 2021.
Chen J, Harding SM, Natesan R, Tian L, Benci JL, Li W, Minn AJ, Asangani IA, Greenberg RA: Cell Cycle Checkpoints Cooperate to Suppress DNA- and RNA-Associated Molecular Pattern Recognition and Anti-Tumor Immune Responses. Cell Reports 32(9): 108080, September 2020.
Rasool RU, Natesan R, Deng Q, Aras S, Effron SS, Velasquez EM, Posimo JM, Lal P, Brady DC, Asangani IA: Targeting transcriptional addiction in anti-androgen refractory castration-resistant prostate cancer. American Association for Cancer Research August 2020.
Zhao SG, Chen WS, Li H, Foye A, Zhang M, Sjöström M, Aggarwal R, Playdle D, Liao A, Alumkal JJ, Das R, Chou J, Hua JT, Barnard TJ, Bailey AM, Chow ED, Perry MD, Dang HX, Yang R, Moussavi-Baygi R, Zhang L, Alshalalfa M, Laura Chang S, Houlahan KE, Shiah YJ, Beer TM, Thomas G, Chi KN, Gleave M, Zoubeidi A, Reiter RE, Rettig MB, Witte O, Yvonne Kim M, Fong L, Spratt DE, Morgan TM, Bose R, Huang FW, Li H, Chesner L, Shenoy T, Goodarzi H, Asangani IA, Sandhu S, Lang JM, Mahajan NP, Lara PN, Evans CP, Febbo P, Batzoglou S, Knudsen KE, He HH, Huang J, Zwart W, Costello JF, Luo J, Tomlins SA, Wyatt AW, Dehm SM, Ashworth A, Gilbert LA, Boutros PC, Farh K, Chinnaiyan AM, Maher CA, Small EJ, Quigley DA, Feng FY: DNA methylation landscapes in advanced prostate cancer. Nature Genetics 52(8): 778-789, August 2020.
Yuan S, Natesan R, Sanchez-Rivera FJ, Li J, Bhanu NV, Yamazoe T, Lin JH, Merrell AJ, Sela Y, Thomas SK, Jiang Y, Plesset JB, Miller EM, Shi J, Garcia BA, Lowe SW, Asangani IA, Stanger BZ: Global regulation of the histone mark H3K36me2 underlies epithelial plasticity and metastatic progression. Cancer Discovery 10(6): 854-871, June 2020.
Deng Q, Natesan R, Arif S, Rasool RU, Liu Y, Wang P, Crammer Z, Mercadante M, Gade T, Cho M, Eisengher K, Grillet N, Asangani IA: Discovery and characterization of LOXHD1 as a highly specific EWS-FLI1 driven oncogene in Ewing sarcoma. American Association for Cancer Research. AACR, June 2020.