Faculty

Irfan A Asangani, Ph.D.

faculty photo
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

Qu Deng, Reyaz ur Rasool, Ronnie M. Russell, Ramakrishnan Natesan, Irfan A. Asangani: Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19. iScience. Cell Press, February 2021 Notes: doi.org/10.1101/2020.10.16.342782.

Asangani I.A., Blair I.A., Van Duyne G., Hilser V.J., Moiseenkova-Bell V., Plymate S., Sprenger C., Wand A.J., Penning T.M. : Using Biochemistry & Biophysics to Extinguish Androgen Receptor Signaling in Prostate Cancer J Bio Chem January 2021.

Mohammad Aarif Siddiqui, Paradesi Naidu Gollavilli, Vignesh Ramesh, Beatrice Parma, Annemarie Schwab, Maria Eleni Vazakidou, Ramakrishnan Natesan,, Ozge Saatci, Ida Rapa, Paolo Bironzo, Harald Schuhwerk, Irfan Ahmed Asangani, Ozgur Sahin, Marco Volante, Paolo Ceppi : Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer. Br J Cancer October 2020 Notes: doi: 10.1038/s41416-020-01095-x. Online ahead of print.

Jie Chen, Shane M Harding, Ramakrishnan Natesan, Lei Tian, Joseph L Benci, Weihua Li, Andy J Minn, Irfan A Asangani, Roger A Greenberg: Cell Cycle Checkpoints Cooperate to Suppress DNA- and RNA-Associated Molecular Pattern Recognition and Anti-Tumor Immune Responses. Cell Rep September 2020 Notes: DOI: 10.1016/j.celrep.2020.108080.

Reyaz ur Rasool, Ramakrishnan Natesan, Qu Deng, Shweta Aras, Samuel Sander Effron, Erick Mitchell Velasquez, Jessica M Posimo, Priti Lal, Donita C Brady, Irfan A Asangani: Targeting transcriptional addiction in anti-androgen refractory castration-resistant prostate cancer. AACR August 2020.

Shuang G Zhao, William S Chen, Haolong Li, Adam Foye, Meng Zhang, Martin Sjöström, Rahul Aggarwal, Denise Playdle, Arnold Liao, Joshi J Alumkal, Rajdeep Das, Jonathan Chou, Junjie T Hua, Travis J Barnard, Adina M Bailey, Eric D Chow, Marc D Perry, Ha X Dang, Rendong Yang, Ruhollah Moussavi-Baygi, Li Zhang, Mohammed Alshalalfa, Laura Chang, Kathleen E Houlahan, Yu-Jia Shiah , Tomasz M Beer, George Thomas, Kim N Chi, Martin Gleave, Amina Zoubeidi, Robert E Reiter, Matthew B Rettig, Owen Witte, M Yvonne Kim, Lawrence Fong, Daniel E Spratt, Todd M Morgan, Rohit Bose, Franklin W Huang , Hui Li, Lisa Chesner, Tanushree Shenoy, Hani Goodarzi, Irfan A Asangani, Shahneen Sandhu, Joshua M Lang, Nupam P Mahajan, Primo N Lara, Christopher P Evans, Phillip Febbo, Serafim Batzoglou, Karen E Knudsen, Housheng H He, Jiaoti Huang, Wilbert Zwart, Joseph F Costello, Jianhua Luo, Scott A Tomlins, Alexander W Wyatt, Scott M Dehm , Alan Ashworth, Luke A Gilbert, Paul C Boutros, Arul M Chinnaiyan, Christopher A Maher, Eric J Small, David A Quigley, Felix Y Feng: The DNA methylation landscape of advanced prostate cancer. Nat Genet August 2020 Notes: DOI: 10.1038/s41588-020-0648-8.

Salina Yuan, Ramakrishnan Natesan, Francisco J Sanchez-Rivera, Jinyang Li, Natarajan V Bhanu, Taiji Yamazoe, Jeffrey H Lin, Allyson J Merrell, Yogev Sela, Stacy K Thomas, Yanqing Jiang, Jacqueline B Plesset, Emma M Miller, Junwei Shi, Benjamin A Garcia, Scott W Lowe, Irfan A Asangani, Ben Z Stanger: Global Regulation of the Histone Mark H3K36me2 Underlies Epithelial Plasticity and Metastatic Progression. Cancer Discov June 2020 Notes: DOI: 10.1158/2159-8290.CD-19-1299.

Qu Deng, Ramakrishnan Natesan, Shehbeel Arif, Reyaz Ur Rasool, Ying Liu, Pei Wang, Zvi Crammer, Michael Mercadante, Terrence Gades, Margaret Cho, Karin Eisengher, Nicolas Grillet, Irfan A Asangani: Discovery and characterization of LOXHD1 as a highly specific EWS-FLI1 driven oncogene in Ewing sarcoma. AACR. AACR, 80(11): 54-55, June 2020.

Samir Devalaraja, Tsun Ki Jerrick To , Ian W Folkert , Ramakrishnan Natesan , Md Zahidul Alam , Minghong Li , Yuma Tada , Konstantin Budagyan , Mai T Dang , Li Zhai , Graham P Lobel , Gabrielle E Ciotti , T S Karin Eisinger-Mathason , Irfan A Asangani , Kristy Weber , M Celeste Simon , Malay Haldar : Tumor-Derived Retinoic Acid Regulates Intratumoral Monocyte Differentiation to Promote Immune Suppression Cell. Cell Press, Volume 180( Issue 6): Pages 1098-1114.e16, 19 March 2020.

Salina Yuan, Ramakrishnan Natesan, Francisco J Sanchez-Rivera, Jinyang Li, Natarajan V Bhanu, Taiji Yamazoe, Jeffrey H Lin, Allyson J Merrell, Stacy K Thomas, Junwei Shi, Ben A Garcia, Scott W Lowe, Irfan A Asangani, Ben Z Stanger: CRISPR screen identifies global regulation of H3K36me2 as an epigenomic mechanism underlying epithelial plasticity in pancreatic ductal adenocarcinoma. AACR December 2019.

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Last updated: 02/16/2021
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