Khalil Ahmed, PhD
Professor, Department of Laboratory Medicine and Pathology
PhD, McGill University, Montreal, Canada (Biochemistry), 1960
MSc (Honours School) First Class and second place in the University, Panjab University Institute of Chemistry, Lahore
BSc (Honours School) First Class, Panjab University, Institute of Chemistry, Lahore 1955
Awards & Recognition
Dr. Ahmed is a Senior Research Career Scientist at Minneapolis VA Health Medical Center. He has a long history of studies on functional biology of protein kinase CK2 (formerly casein kinase II or 2) and is considered a leader in this field. CK2 has emerged as a major signal involved in diverse cellular functions of health and disease and may be a universal target for cancer drug development.
Ahmed began his investigation of CK2 in studies of prostate cancer and has subsequently studied CK2 involvement in head and neck cancer, breast cancer, and melanoma.He was first to characterize CK2’s intracellular phosphorylation signaling mechanism and then delineated the role of CK2 as a suppressor of cell death, including apoptosis or programmed cell death, in normal and neoplastic cells. The latter activity of CK2 is now regarded as one of its most important functions.
Ahmed’s current research, in collaboration with fellow investigators at the VA Health Care System and private industry, focuses on studies of the mechanisms of CK2 regulation of cell death and on developing molecular therapeutic strategies using a nanomedicine approach for the treatment of prostate and other cancers.
CK2 signal plays a critical role in cell growth and proliferation. Studies by Ahmed and his colleagues show that CK2 is highly expressed in proliferating cells including cancer cells, and loss of CK2 activity results in cell death. All cancers they have analyzed demonstrate consistently up-regulated CK2, which is distinct from the pattern of up- and down-regulation found in normal cells, a kind of regulatory homeostasis. The ability of CK2 to promote cell growth as well as suppress apoptosis links the kinase to cancer biology as cancer cells are characterized by dysregulation not only of proliferation but also of apoptosis, which means that this signal has the potential of serving as a target for inducing apoptosis in cancer cells. Ahmed originally proposed CK2 as a target for cancer therapy, which is now being pursued by several groups.Although CK2 is present in both the nucleus and cytoplasm, in cancer cells it tends to concentrate in the nucleus.Ahmed’s laboratory has found that many of the CK2 functions related to cell growth and cell death are mediated via its signaling to structures in the cell’s nucleus such as chromatin and nuclear matrix. Ahmed and co-investigators Janeen Trembley, Betsy Kren and others are delineating the mechanism of these signaling events. Recently they found that the CK2 activity affects the membrane potential of mitochondria, which is associated with rapid intracellular calcium flux; mitochondria are the classical mediators of cell death.
Ahmed and his colleagues have also established proof of principle for the potential targeting of CK2 for cancer therapy by antisense or siRNA-mediated molecular downregulation of CK2.In collaboration with Gretchen Unger of GeneSegues, Inc., they are employing a novel nanoparticle approach for delivering CK2 antisense or siRNA oligonucleotides specifically to the tumor cells in vivo. They have developed an entirely original nanocapsule strategy to deliver the treatment to cancer cells, thereby avoiding normal cell damage and heightened toxicity characteristic of conventional chemotherapy. Unger invented a neutrally charged protein nanocapsule particle less than 50 nanometers in size that carries an anti-CK2 nucleic acid to induce cell death by prohibiting the formation of CK2, an essential protein for cell survival.The researchers created this nanocapsule using the tenfibgen protein subdomain of the extracellular matrix molecule tenascin C, which is readily recognized by the surface receptors for tenascin in cancer cells, allowing the nanocapsule to enter the cell. Upon entry the cell breaks down the capsule’s shell releasing the anti-CK2 nucleic acid.Cancer cells begin to die when CK2 expression is reduced, typically at as little as 30 percent of CK2 protein loss.
Ahmed is encouraged by results from small- and large-animal studies of the potential for a nanomedicine strategy for treating cancer by selectively inhibiting CK2 expression in cancer cells.He is particularly interested in its potential for treating metastatic bone cancer arising from prostate cancer.This type of bone cancer is currently untreatable.
- Cannon CM, Trembley JH, Kren BT, Unger GM, O’Sullivan MG, Cornax I, Modiano JF, Ahmed K: Therapeutic targeting of protein kinase CK2 gene expression in feline oral squamous cell carcinoma: A naturally occurring large animal model of head and neck cancer. Human Gene Therapy Clinical Development, Volume 28, Number 2, 2017. DOI: 10.1089/humc.2017.008
- Trembley JH, Kren BT, Abedin MJ, Vogel RI, Cannon CM, Unger, GM, Ahmed K: CK2 Molecular Targeting —Tumor Cell-Specific Delivery of RNAi in Various Models of Cancer. Pharmaceuticals 2017, 10, 25; doi:10.3390/ph10010025
- Ahmed K, Kren BT, Abedin MJ, Vogel RI, Shaughnessy DP, Nacusi L, Korman VL, Li Y, Dehm SM, Zimmerman CL, Niehans GA, Unger GM, Trembley JH. CK2 targeted RNAi therapeutic delivered via malignant cell-directed tenfibgen nanocapsule: dose and molecular mechanisms of response in xenograft prostate tumors. Oncotarget. 2016 Aug 20. doi: 10.18632/oncotarget.11442. [Epub ahead of print]
- Qaiser F, Trembley JH, Sadiq S, Muhammad I, Younis R, Hashmi SN, Murtaza B, Rector TS, Naveed AK, Ahmed K. Examination of CK2? and NF-?B p65 expression in human benign prostatic hyperplasia and prostate cancer tissues. Mol Cell Biochem. 2016 Sep;420(1-2):43-51. doi: 10.1007/s11010-016-2765-3. Epub 2016 Jul 19.
Ahmed, Khalil, ‘High Hopes for Health’, International Innovation, November 2013, (Research Media, UK, pp 15-17) ISSN 2051-8528.
- Trembley JH, Wu J, Unger GM, Kren BT, Ahmed K: CK2 suppression of apoptosis and its implications in cancer biology and therapy. In Pinna LA (Ed.) The Wiley-IUBMB Series on Biochemistry and Molecular Biology: Protein Kinase CK2. ISBN: 978-0-470-96303-6, January 2013, Wiley-Blackwell. Pp 319-333.
- Kramerov AA, Ahmed K, Ljubimov A. 2012. Cell rounding in cultured human astrocytes and vascular endothelial cells upon inhibition of CK2 is mediated by actomyosin cytoskeleton alteration. J Cell Biochem. J Cell Biochem. 13(9):2948-56.
- Unger G, Trembley J, Kren B, Ahmed K: Nanoparticles in Cancer Therapy. In: Schwab M. (Ed.) Encyclopedia of Cancer: SpringerReference (www.springerreference.com). Springer-Verlag Berlin Heidelberg, 2012. DOI: 10.1007/SpringerReference_175620 2012-03-05 10:28:01 UTC
- Ahmed K: Nanocapsules. In: Schwab M. (Ed.) Encyclopedia of Cancer: SpringerReference (www.springerreference.com). Springer-Verlag Berlin Heidelberg, 2012. URL: http://www.springerreference.com/docs/html/chapter... 2012-02-27 10:34:43 UTC
- Trembley JH, Unger GM, Korman VL, Tobolt DK, Kazimierczuk Z, Pinna LA, Kren BT, Ahmed K. 2012. Nanoencapsulated anti-CK2 small molecule drug or siRNA specifically targets malignant cancer but not benign cells. Cancer Letters 315: 48–58,
- Ahmed K, Issinger O-G, Niefind K. 2011. Protein kinase CK2: A catalyst for biology, medicine and structural biochemistry. Mol Cell Biochem 356: 1-3.
- Trembley JH, Unger G, Tobolt DK, Korman VL, Wang G, Ahmad KA, Slaton J, Kren BT, Ahmed K. 2011. Systemic administration of antisense oligonucleotides simultaneously targeting CK2a and a? reduces primary prostate xenograft tumors in mice. Molec Cell Biochem 356: 21-35.
- Kramerov A, Golub AG, Bdzhola VG, Yarmoluk SM, Ahmed K, Bretner M, Ljubimov AV: 2011. Treatment of cultured human astrocytes and vascular endothelial cells with protein kinase CK2 inhibitors induces early changes in cell shape and cytoskeleton. Mol Cell Biochem. 349: 125–137.
- Slaton JW, Ahmed K, Unger GM, Davis A, Sloper D: Casein Kinase 2 Antisense Therapy, in www.uspto.gov. 2010, Regents of the University of MN: U.S.A. United States Patent 7,741,304.
- Trembley JH, Chen Z, Unger G, Slaton J, Kren BT, Van Waes C, Ahmed K: 2010. Emergence of Protein Kinase CK2 as a Key Target in Cancer Therapy. BioFactors 36(3): 187-195.
- Wang G, Pan Y, Ahmad KA, Ahmed K: 2010. Protein B23/Nucleophosmin/Numatrin dynamics in relation to modulation of Protein Kinase CK2 and Apoptotic Activity in Prostate Cells. Biochemistry 49 (18): 3842–3852.
- Brown MS, Diallo OT, Hu M, Ehsanian R, Yang X, Arun P, Lu H, Korman V, Unger G, Ahmed K, Van Waes C, Chen Z: 2010. CK2 modulation of NF-kB, TP53 and the malignant phenotype in head and neck cancer by anti-CK2 oligonucleotides in vitro or in vivo via sub-50 nm nanocapsules. Clin Canc Res 16: 2295-2307.
- Unger GM, Kren BT, Korman VL, Kimbrough TG, Vogel RI, Ondrey FG, Trembley JH, Ahmed K: Mechanism and efficacy of sub-50 nm tenfibgen nanocapsules for cancer cell-directed delivery of anti-CK2 RNAi to primary and metastatic squamous cell carcinoma. Mol Cancer Ther 13:2018-2029, August 2014; Published OnlineFirst May 27, 2014; doi:10.1158/1535-7163.MCT-14-0166 Ahmed, Khalil Page 31
- Qaiser F, Trembley JH, Kren BT, Wu J-J, Naveed AK, Ahmed K: Protein kinase CK2 inhibition induces cell death via early impact on mitochondrial function. J Cell Biochem 115: 2103–2115, 2014. DOI: 10.1002/jcb.24887 222. Trembley JH, Unger GM, Korman VL, Abedin MJ, Nacusi LP, Vogel RI, Slaton JW, Kren BT, Ahmed K: Tenfibgen ligand nanoencapsulation delivers bi-functional antiCK2 RNAi oligomer to key sites for prostate cancer targeting. PLoS ONE 9(10): e109970. doi:10.1371/journal.pone.0109970
- Trembley JH, Unger GM, Gomez OC, Abedin MJ, Korman VL, Vogel RI, Niehans G, Kren BT, Ahmed K: Tenfibgen-DMAT nanocapsule treatment of prostate cancer xenografts inhibits tumor proliferation. Mol Cell Pharm 6(2): 15-25, 2014. DOI: 10.4255/mcpharmacol.14.02
- Kren BT, Abedin MJ, Unger GM, Vogel RI, Ahmed K, Trembley JH. Preclinical evaluation of cyclin dependent kinase 11 (CDK11) and casein kinase 2 (CK2) survival kinases as RNA interference targets for triple negative breast cancer therapy. Breast Cancer Research.2015, 17:19. DOI: 10.1186/s13058-015-0524-0
- Trembley JH, Qaiser F, Kren BT, Ahmed K: CK2 – A global regulator of cell death. In: Springer International Publishing Switzerland 2015. K. Ahmed et al. (eds.), Protein Kinase CK2 Cellular Function in Normal and Disease States, Advances in Biochemistry in Health and Disease 12, DOI 10.1007/978-3-319-14544-0_10 226. Ahmed K, Unger GM, Kren BT, Trembley JH: Targeting CK2 for cancer therapy using a nanomedicine approach. In: Springer International Publishing Switzerland 2015. K. Ahmed et al. (eds.), Protein Kinase CK2 Cellular Function in Normal and Disease States, Advances in Biochemistry in Health and Disease 12, DOI 10.1007/978- 3-319-14544-0_17
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