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7Signaling Mechanisms that Control Cellular Functions and Disease
Our goal is to understand how signaling pathways regulate cancer and other diseases. The current focus is on understanding the mechanisms of cellular signaling and applying this knowledge to development of drugs that cure disease. Recently spatial organization of cellular signals and messengers such as phosphoinositide messengers has been shown to be fundamental in regulating cellular events and diseases.
The work is currently focused on:
- The control of nuclear signaling involving p53 known as the “Guardian of the Genome”. Wildtype p53 is a tumor suppressor that protects cells from DNA mutations, BUT p53 is mutated in most cancers and mutant p53 acts as oncogenic protein that drive cancers. We discovered the underlying mechanism for mutant p53’s oncogenic properties and are working on drugs that will block this.
- The roles of trafficking in regulation of growth receptor signaling pathways that control cell proliferation and metastasis.
For these studies we use many interdisciplinary approaches, including cell biology, biochemistry, structural biology, biophysics, genetics, molecular biology, high-resolution microscopy and translational cancer biology.
Our research foundation is basic research, yet we also seek to define how the basic signaling and regulatory pathways that we have discovered are fundamental to a wide variety of human epithelial cancers, including breast, head and neck cancers and lung cancers. The roles of nuclear lipid 3rd messengers in gene expression represents a fundamental discovery with implications to all aspects of human biology and disease.
An emphasis of our group is the training of young scholars in scientific research.
Anderson Lab News
July 28, 2022
Very nice piece about our recent work that has gone national!
July 24, 2022
Mo’s breakthrough paper on the p53-Akt pathway that is in review at Nature Cell Biology. This is a collaborative project with the Cryns lab and has initiate novel cancer drug discovery approaches.
Chen M, Choi S, Wen T, Chen C, Thapa N, Cryns VL, Anderson RA. (2022) A p53-Phosphoinositide Signalosome Regulates Nuclear Akt Activation. Nature Cell Biology, 24(7):1099-1113. PMID: 35798843.
See also https://news.wisc.edu/unexpected-link-between-most-common-cancer-drivers-may-yield-more-effective-drugs/; In the top 2% of articles scored by Altmetric, https://www.nature.com/articles/s41556-022-00949-1/metrics.
May 6, 2022
Mo archives her breakthrough paper on the p53-Akt pathway that is in review at Nature Cell Biology. This is a collaborative project with the Cryns lab.
Chen, M., Choi, S., Wen, T., Chen, C., Thapa, N., Cryns, LV. and Anderson, R.A. (2021) A p53-Phosphoinositide Signalosome Regulates Nuclear Akt Activation. bioRxiv. doi: https://doi.org/10.1101/2021.09.17.460854
March 1, 2021
Mo published her innovation technics paper on fluorescence proximity ligation assay. This is a collaborative project with the Cryns lab.
Chen M, Horn HT, Wen T, Cryns VL, Anderson RA. (2021) Assessing in situ phosphoinositide–protein interactions through fluorescence proximity ligation assay in cultured cells. Methods Molecular Biology 2251: 133-142. doi: 10.1007/978-1-0716-1142-5_9.
January 1, 2020
Wei published her papers on the IQGAP1 in Head and Neck cancers. This is a collaborative project with the Lambert lab.
Wei T, Choi S, Buehler D, Anderson RA, Lambert PF. A PI3K/AKT Scaffolding Protein, IQ Motif-Containing GTPase Associating Protein 1 (IQGAP1), Promotes Head and Neck Carcinogenesis. (2020) Clin Cancer Res. 26(1):301-311. PMID: 31597661; PMCID: PMC6942630.
Wei T, Choi S, Buehler D, Lee D, Ward-Shaw E, Anderson RA, Lambert PF. Role of IQGAP1 in Papillomavirus-Associated Head and Neck Tumorigenesis. Cancers (Basel). 2021 May 10;13(9):2276. doi: 10.3390/cancers13092276. PMID: 34068608
November 22, 2020
Narendra published his breakthrough paper on the spatial location of PI 3-kinase signaling by receptors and mutant PI 3-kinase. This changes the dogma of PI 3-kinase signaling at the plasma membrane.
Thapa N, Chen M, Horn HT, Choi S, Wen T, Anderson RA. (2020) Phosphatidylinositol-3-OH kinase signalling is spatially organized at endosomal compartments by microtubule-associated protein 4. Nature Cell Biology 22(11):1357-70. Epub 2020/11/04. doi: 10.1038/s41556-020-00596-4. PubMed PMID: 33139939; PMCID: PMC8647654
See also News and Views: Batrouni AG, Baskin JM. A MAP for PI3K activation on endosomes. Nature Cell Biology 22(11):1292-4; Foley, JF MAPping PI3K signaling to endosomes Science Signaling 13, Issue 658, Rated exceptional by F1000Prime; In the top 2% of articles scored by Altmetric.
February 19, 2020
Mo’s key paper on nuclear stress response pathways is published
Chen, M., Wen, T., Horn, H.T., Chandrahas, VK., Thapa, N., Choi, S., Cryns, V.L., and Anderson, R.A. (2020) The Nuclear Phosphoinositide Response to Stress. Cell Cycle, Jan 5:1-22. PMID: 31902273 doi: 10.1080/15384101.2019.1711316.
May 10, 2019
Collaborative paper with Paul Lambert’s group is published
Wei T, Choi S, Buehler D,, Anderson R, Lambert P. (2019) Role of IQGAP1 in Head and Neck Carcinogenesis. Clinical Cancer Research 26(1):301-311. PMID: 31597661
November 18, 2019
Collaborative paper between past postdoc Rakesh Laishram and the Anderson lab is now published. Rahesh is now a Professor at Rajiv Gandhi Centre for Biotechnology
Sudheesh A.P., Mohan, N., Nimmy F., Laishram, R.S. and Anderson, R.A. (2019) Star-PAP controlled alternative polyadenylation coupled poly(A) tail length regulates protein expression in hypertrophic heart. Nucleic Acids Research 47(20):10771-10787. PMID: 31598705; PMCID: PMC6847588
May 21, 2019
Narendra’s paper is paper is now published in Advances in Biological Regulation.
Thapa N, Horn HT, Anderson RA. (2019) Phosphoinositide spatially free AKT/PKB activation to all membrane compartments. Adv Biol Regul, 72:1-6. PMID: 30987931
May 11, 2019
Mo’s paper is paper is now published in Nature Cell Biology.
Chen M, Wen T, Choi S, Thapa N, Jung O, Lambert P, Rapraeger AC, Anderson RA. (2019) The Specificity of IQGAP1 Toward the PI3K-Akt Pathway is Dependent on the IQ3 motif. Scientific Reports, 9(1):9126; PMID: 31235839; PMCID: PMC6591252
April 21, 2019
Choi’s paper is paper is now published in Nature Cell Biology.
Choi, S., Chen, M., Cryns, V. and Anderson, R.A. (2019) A Nuclear Phosphoinositide Kinase Complex that Regulates p53. Nature Cell Biology 21, 462-475. PMID: 30886346
See also News release University of Wisconsin-Madison "UW team finds key to common cancer pathway in discovery that could unlock new therapies"; ScienceDaily, March 18, 2019; 13 other news articles including Wisconsin State Journal and Journal Sentinal; Rated exceptional by F1000Prime, 02 May 2019; In the top 2% of articles scored by Altmetric; see also https://spectrumnews1.com/wi/milwaukee/news/2019/04/05/uw-madison-scientists-discover-cancer-pathway-breakthrough?cid=share_fb&fbclid=IwAR1fIQC8VCVAybsQiWi_1HX2xHlYTPhAd9ua6wOLsYt5PkhAhwkXzOKMVik
February 8, 2018
Choi’s paper is paper is now published in Advances in Biological Regulation.
Choi S, Houdek X, Anderson RA. (2018) Phosphoinositide 3-kinase pathways and autophagy require phosphatidylinositol phosphate kinases. Adv Biol Regul, 68, 31-38.
October 23, 2017
Narendra’s paper is now published in Developmental Cell.
Thapa, N. and Anderson, R. A. (2017) PLD and PA Take MT1-MMP For a Metastatic Ride. Dev. Cell. 43, 117-119. PMID:29065302
September 6, 2017
Wiemin Li’s paper is now published in NAR. Shows that ~40% of human genes are controlled by Star-PAP
Li*, W., Laishram*, R.S., Ji*, Z., Hoque, M., Tian, B., and Anderson, R.A. (2017) Distinct regulation of alternative polyadenylation and gene expression by nuclear poly(A) polymerases. *Co-first authors. Nucleic Acids Research, 45, 8930–8942. PMID: 28911096, PMCID: PMC5587728
May 12, 2017
Jay Tan’s paper is now published in Science.
Tan, X. and Anderson, R. A. (2017) Keeping in touch with the ER network. Science 356, 584-585. PMID: 28495716
March 20, 2017
Choi’s News and Views in now published. Congratulations!
February 16, 2017
Narendra’s paper is now accepted at Oncogene. Congratulations to all the authors.
November 23, 2016
Nine news articles that cited Suyong’s paper that is published in Nature Cell Biology. These include a news release from the University of Wisconsin, Cancer signaling pathway could illuminate new avenue to therapy and eight others that where noted by the Nature Website.
In addition, there was a News and Views that was written about this paper.
November 21, 2016
Suyong’s paper is now accepted at Nature. Congratulations to all the authors. Choi, S., Hedman, A.C. Sayedyahossein, S. Thapa, N. Sacks, D.B. and Anderson, R.A. (2016) Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation by scaffolded phosphoinositide kinases. Nature Cell Biology 18, 1324–1335. PMID: 27870828.
October 7, 2016
Yue’s paper is now accepted at JBC. Congratulations to all the authors. Sun, M., Cai, J., Anderson, R.A., and Sun, Y. (2016) Type I Gamma Phosphatidylinositol Phosphate 5-kinase i5 Controls the Ubiquitination and Degradation of a Tumor Suppressor Mitogen-inducible Gene 6. J. Biol. Chem. 291(41):21461-21473. PMID: 27557663, PMCID: PMC5076818
June 20, 2016
Narendra’s paper is now accepted at Trends in Cancer. Congratulations to all the authors. Thapa, N., Tan, X., Choi, S., Rapreager, A. Lambert, P. and Anderson, R. A. (2016) The Hidden Conundrum of Phosphoinositide Signaling in Cancer. Trends in Cancer, 2, 378–390. PMID: 27819060, PMCID: PMC5094282
January 27, 2016
Xiaojun’s paper is now accepted at Trends in Cell Biology. Congratulations to all the authors. Tan, X., Lambert, P.F., Rapraeger, A.C. & Anderson, R.A. (2106) Stress-Induced EGFR Trafficking: Mechanisms, Functions, and Therapeutic Implications. Trends in Cell Biology, 26, 352-66. PMID: 26827089, doi:10.1016/j.tcb.2015.12.006. PMC Journal.
November 23, 2015
Xiaojun’s paper is now accepted at PNAS. Congratulations to all the authors. Tan X, Thapa, N., Liao, Y. and Anderson R.A. (2016) PtdIns(4,5)P₂ Signaling Regulates ATG14 and Autophagy. Proc. Natl. Acad. Sci. U.S.A. 113, 10896-901. PMID: 27621469, PMCID: PMC5047215
November 15, 2015
Xiaojun’s paper is now accepted at J. Cell Science. Congratulations to all the authors. Tan, X., Thapa, N., Choi, S., and Anderson, R.A. (2015) Emerging roles of PtdIns(4,5)P₂ - beyond the plasma membrane. J. Cell Science, 128(22), 4047-56. PMID: 26574506, PMCID: PMC4712784
October 28, 2015
Suyong’s paper is now accepted at Adv Enzyme Regul. Congratulations to all the authors. Choi, S. and Anderson, R.A. (2015) IQGAP1 is a Phosphoinositide Effector and Kinase Scaffold. Adv Enzyme Regul: S2212-4926(15)30027-0. PMID: 26554303, PMCID: PMC4729663
July 2, 2015
Rakesh’s paper is now accepted at NAR. Congratulations to all the authors. Mohan N, Sudheesh AP, Francis N, Anderson. R.A. and Laishram, R.S., (2015) Mohan N, Sudheesh AP, Francis N, Anderson. R.A. and Laishram, R.S., (2015) Phosphorylation regulates the Star-PAP-PIPKIα interaction and directs specificity toward mRNA targets. Nucleic Acids Res. 43, 7005-20. PMID: 26138484, PMCID: PMC4538844
June 12, 2015
Narendra’s paper is now accepted at JBC. Congratulations to all the authors. Thapa, N., Choi, S., Tan, X., and Anderson, R. A. (2014) Phosphatidylinositol Phosphate 5-Kinase Igamma and PI3K/Akt Signaling Couple to Promote Oncogenic Growth. J. Biol. Chem.
January 16, 2015
Suyong’s paper is now accepted at BBA. Congratulations to all the authors. Choi, S., Thapa, N., Tan, X., Hedman, A.C. & Anderson, R.A. (2015) PIP kinases define PI4,5P₂signaling specificity by association with effectors. Biochimica et biophysica acta 1851, 711-723. PMID: 25617736, PMCID: PMC4380618
January 15, 2015
Xiaojun’s paper is now accepted at Cell. Congratulations to all the authors. Tan, X., Thapa, N., Sun, Y. & Anderson, R.A. (2015) A kinase-independent role for EGF receptor in autophagy initiation. Cell 160, 145-160. PMID: 25594178, PMCID: PMC4297316.
January 15, 2015
UW-Madison scientists find how many cancers may evade treatment.
December 12, 2014
Xiaojun’s paper is now accepted at EMBO. Congratulations to all the authors. Tan X, Sun Y, Thapa N, Liao Y, Hedman AC, Anderson RA. (2015) LAPTM4B is a PtdIns(4,5)P₂effector that regulates EGFR signaling, lysosomal sorting, and degradation. The EMBO Journal. 34, 475-90. PMID: 25588945, "PMCID: PMC4331002
November 19, 2014
Xiaojun’s paper is now accepted at Cell. Congratulations to all the authors.
Xiaojun Tan, Narendra Thapa, Yue Sun and Richard A Anderson (2014) A Kinase Independent Role for the EGF Receptor in Autophagy Initiation. In press, Cell.
July 27, 2014
Group attended the FASEB meeting on, “FASEB 2014- Lipids and Lipid Regulated Kinases in Cancer, July 27-August 1, 2014 in Steamboat Springs, Colorado. Richard is speaking, “Lipid messengers in the nucleus control PTEN expression.”
Narendra Thapa is a speaker also “Phosphatidylinositol Phosphate 5-Kinase gamma (PIPKIγ) Regulates Migration and Anchorage-independent Growth of Tumor Cells.
May 25, 2014
Nick Schills paper is in press at J. Cell Science and Emphasized in the JCS Snapshot. Congratulations to all the authors.
Schill, N.J., Hedman, A.C., Choi, S. and Anderson, R.A. (2014) Isoform 5 of PIPKIγ Regulates the Endosomal Trafficking and Degradation of E-cadherin. J. Cell Science. 127, 2189–2203 PMID: 24610942 PMCID: PMC4021470 Emphasized in the JCS Snapshot.
May 5, 2013
Suyong Choi paper is accepted at The EMBO Journal. Have a good read.
Choi, S., Thapa, N., Sacks, D., and Anderson, R.A. (2013) Directional Cell Migration is Regulated by an IQGAP1 and Type Iγ Phosphatidylinositol Phosphate Kinase Signaling Nexus. The EMBO Journal 32, 2617-30, PMID: 23982733, PMCID: PMC3791370
April 7, 2013
Narendra Thapa’s paper is accepted at J. Biol. Chemistry. Really nice paper!
Thapa, N., Choi, S., Sun, Y, and Anderson, R. A. (2013) Phosphatidylinositol Phosphate 5-Kinase Ii2 in Association with Src Controls Anchorage-independent Growth of Tumor Cells. J. Biol. Chem. 288, 34707–34718, PMID: 24151076, PMCID: PMC3843082
March 3, 2013
Collaborative paper with Tim Hughes accepted in Nature.
Ray D, Kazan H, Cook KB, Weirauch MT, Najafabadi HS, Li X, Gueroussov S, Albu M, Zheng H, Yang A, Na H, Irimia M, Matzat LH, Dale RK, Smith SA, Yarosh CA, Kelly SM, Nabet B, Mecenas D, Li W, Laishram RS, Qiao M, Lipshitz HD, Piano F, Corbett AH, Carstens RP, Frey BJ, Anderson RA, Lynch KW, Penalva LO, Lei EP, Fraser AG, Blencowe BJ, Morris QD, Hughes TR. (2013) A compendium of RNA-binding motifs for decoding gene regulation. Nature. 499, 172-177. doi: 10.1038/nature12311. PMID: 23846655. NIHMSID: NIHMS554111.
Rated must read by Faculty of 1000 during July 2013: New alert, Medical News Today
October 3, 2012
Thapa, N., Sun, Y, Schramp, M., Choi, S., Ling, K., and Anderson, R. A. (2012) Phosphoinositide Signaling Regulates the Exocyst Complex and Polarized Integrin Trafficking in Directionally Migrating Cells. Dev. Cell, 22, 116–130. PMID: 22264730, PMCID: PMC3266520
Rated must read by Faculty of 1000 during February - May 2012.
February 3, 2012
Xiaojun Tan is awarded a Howard Hughes International Predoctoral Fellowship, 1 of 40 awarded nation wide. Congratulations Xiaojun.