Alison Axtman

Research Assistant Professor (UNC) - Principal Investigator (SGC)

University of North Carolina at Chapel Hill
(216) 470-7201

Alison Axtman is a synthetic medicinal chemist with more than 10 years of research experience working at the interface of chemical and biology. Alison earned her PhD in Medicinal Chemistry at the University of Kansas, and carried out her post-doctoral training in the Department of Chemistry at Stanford University. Alison’s research has focused on the synthesis of small molecules that selectively modulate proteins implicated in disease-propagating pathways. As a member of the GSK Chemical Biology department, she led a program to understand the molecular basis of immune modulation by a class of natural products and developed analogs with improved drug properties. Alison is currently a Research Assistant Professor in the Chemical Biology and Medicinal Chemistry Department in the UNC Eshelman School of Pharmacy. At the SGC-UNC, she leads the design of novel chemical probes for understudied protein kinases that will be openly shared with collaborators to facilitate target discovery in human disease-relevant assays. When she’s not in the lab, Alison can be most often found at the gym preparing for the next CrossFit or GRID competition with her teammates.

 

2014

Function through bio-inspired, synthesis-informed design: step-economical syntheses of designed kinase inhibitors
Wender, P. A.; Axtman, A. D.; Golden, J. E.; Kee, J.-M.; Sirois, L. E.; Quiroz, R. V.; Stevens, M. C.
Chem. Front. . 2014 1166-1171. doi:
PMID:25632347

2012

Combined inhibition of Wee1 and Hsp90 activates intrinsic apoptosis in cancer cells
Iwai, A.; Bourboulia, D.; Mollapour, M.; Jensen-Taubman, S.; Lee, S.; Donnelly, A. C.; Yoshida, S.; Miyajima, N.; Tsutsumi, S.; Smith, A. K.; Sun, D.; Wu, X.; Blagg, B. S.; Trepel, J. B.; Stetler-Stevenson, W. G.; Neckers, L.
Cell Cycle. 2012 3649-55. doi:
PMID:22935698

2011

Development and characterization of a novel C-terminal inhibitor of Hsp90 in androgen dependent and independent prostate cancer cells
Eskew, J. D.; Sadikot, T.; Morales, P.; Duren, A.; Dunwiddie, I.; Swink, M.; Zhang, X.; Hembruff, S.; Donnelly, A.; Rajewski, R. A.; Blagg, B. S.; Manjarrez, J. R.; Matts, R. L.; Holzbeierlein, J. M.; Vielhauer, G. A.
BMC Cancer . 2011 11:468.. doi:10.1186/1471-2407-11-468
PMID:22039910

A novel C-terminal HSP90 inhibitor KU135 induces apoptosis and cell cycle arrest in melanoma cells
amadi, A. K.; Zhang, X.; Mukerji, R.; Donnelly, A. C.; Blagg, B. S.; Cohen, M. S.
Cancer Lett. 2011 158-67. doi:10.1016/j.canlet.2011.07.031
PMID:21924824

Engineering an antibiotic to fight cancer: Optimization of the novobiocin scaffold to produce anti-proliferative agents
Zhao, H; Donnelly, A. C.; Kusuma, B. R.; Brandt, G. E. L.; Brown, D.; Rajewski, R. A.; Vielhauer, G.; Holzbeierlein, J.; Blagg, B. S. J.
Med. Chem.. 2011 3839-3853. doi:10.1021/jm200148p
PMID:21553822

A systematic protocol for the characterization of Hsp90 modulators
Matts, R. L.; Brandt, G. E.; Lu, Y.; Dixit, A.; Mollapour, M.; Wang, S.; Donnelly, A. C.; Neckers, L.; Verkhivker, G.; Blagg, B. S.
Med. Chem. Lett. . 2011 684-92. doi:10.1016/j.bmc.2010.10.029
PMID:21129982

2010

Swe1/Wee1-dependent tyrosine phosphorylation of Hsp90 regulates distinct facets of chaperone function
Mollapour, M.; Tsutsumi, S.; Donnelly, A. C.; Beebe, K.; Tokita, M. J.; Lee, M.-J.; Lee, S.; Morra, G.; Bourboulia, D.; Scroggins, B. T.; Colombo, G.; Blagg, B. S.; Panaretou, B.; Stetler-Stevenson, W. G.; Trepel, J. B.; Piper, P. W.; Prodromou, C.; Pearl, L. H.; Neckers, L.
Cell. 2010 333-43. doi:10.1016/j.molcel.2010.01.005
PMID:20159553

Characterization of a novel novobiocin analogue as a putative C-terminal inhibitor of heat shock protein 90 in prostate cancer cells
Matthews, S. B.; Vielhauer, G. A.; Manthe, C. A.; Chaguturu, V. K.; Szabla, K.; Matts, R. L.; Donnelly, A. C.; Blagg, B. S.; Holzbeierlein, J. M.
Prostate. 2010 27-36. doi:10.1002/pros.21035
PMID:19739131

Cytotoxic sugar analogues of an optimized novobiocin scaffold
Donnelly, A. C.; Zhao, H.; Kusuma, B. R.; Blagg, B. S. J.
Chem. Comm. . 2010 165-170. doi:
PMID:

2009

KU135, a novel novobiocin-derived C-terminal inhibitor of Hsp90, exerts potent antiproliferative effects in human leukemic cells
Shelton, S. N.; Shawgo, M. E.; Comer, S. B.; Lu, Y.; Donnelly, A. C.; Szabla, K.; Tanol, M.; Vielhauer, G. A.; Rajewski, R. A.; Matts, R. L.; Blagg, B. S.; Robertson, J. D.
Mol Pharmacol.. 2009 1314-22. doi:10.1124/mol.109.058545
PMID:19741006

2023

Open drug discovery in Alzheimer's disease.
Axtman AD, Brennan PE, Frappier-Brinton T, Betarbet R, Carter GW, Fu H, Gileadi O, Greenwood AK, Leal K, Longo FM, Mangravite LM, Edwards AM, Levey AI
Alzheimers Dement (N Y). 22.05.2023 9(2):e12394. doi: 10.1002/trc2.12394
PMID: 37215505

Discovery of a Potent and Selective CDKL5/GSK3 Chemical Probe That Is Neuroprotective.
Ong HW, Liang Y, Richardson W, Lowry ER, Wells CI, Chen X, Silvestre M, Dempster K, Silvaroli JA, Smith JL, Wichterle H, Pabla NS, Ultanir SK, Bullock AN, Drewry DH, Axtman AD
ACS Chem Neurosci. 21.04.2023 . doi: 10.1021/acschemneuro.3c00135
PMID: 37084253

Discovery of a Potent and Selective Naphthyridine-Based Chemical Probe for Casein Kinase 2.
Davis-Gilbert ZW, Krämer A, Dunford JE, Howell S, Senbabaoglu F, Wells CI, Bashore FM, Havener TM, Smith JL, Hossain MA, Oppermann U, Drewry DH, Axtman AD
ACS Med Chem Lett. 13.04.2023 14(4):432-441. doi: 10.1021/acsmedchemlett.2c00530
PMID: 37077385

Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis.
Bashore FM, Marquez AB, Chaikuad A, Howell S, Dunn AS, Beltran AA, Smith JL, Drewry DH, Beltran AS, Axtman AD
Sci Rep. 14.04.2023 13(1):6118. doi: 10.1038/s41598-023-32854-4
PMID: 37059819

2022

Identification and Utilization of a Chemical Probe to Interrogate the Roles of PIKfyve in the Lifecycle of β-Coronaviruses.
Drewry DH, Potjewyd FM, Bayati A, Smith JL, Dickmander RJ, Howell S, Taft-Benz S, Min SM, Hossain MA, Heise M, McPherson PS, Moorman NJ, Axtman AD
J Med Chem. 16.09.2022 . doi: 10.1021/acs.jmedchem.2c00697
PMID: 36111834

Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses.
Yang X, Dickmander RJ, Bayati A, Taft-Benz SA, Smith JL, Wells CI, Madden EA, Brown JW, Lenarcic EM, Yount BL, Chang E, Axtman AD, Baric RS, Heise MT, McPherson PS, Moorman NJ, Willson TM
ACS Chem Biol. 19.06.2022 . doi: 10.1021/acschembio.2c00378
PMID: 35723434

Protein proximity networks and functional evaluation of the Casein Kinase 1 γ family reveal unique roles for CK1γ3 in WNT signaling.
Agajanian MJ, Potjewyd FM, Bowman BM, Solomon S, LaPak KM, Bhatt DP, Smith JL, Goldfarb D, Axtman AD, Major MB
J Biol Chem. 26.04.2022 101986. doi: 10.1016/j.jbc.2022.101986
PMID: 35487243

AD Informer Set: Chemical tools to facilitate Alzheimer's disease drug discovery.
Potjewyd FM, Annor-Gyamfi JK, Aubé J, Chu S, Conlon IL, Frankowski KJ, Guduru SKR, Hardy BP, Hopkins MD, Kinoshita C, Kireev DB, Mason ER, Moerk CT, Nwogbo F, Pearce KH, Richardson TI, Rogers DA, Soni DM, Stashko M, Wang X, Wells C, Willson TM, Frye SV, Young JE, Axtman AD
Alzheimers Dement (N Y). 28.04.2022 8(1):e12246. doi: 10.1002/trc2.12246
PMID: 35475262

Use of AD Informer Set compounds to explore validity of novel targets in Alzheimer's disease pathology.
Potjewyd FM, Annor-Gyamfi JK, Aubé J, Chu S, Conlon IL, Frankowski KJ, Guduru SKR, Hardy BP, Hopkins MD, Kinoshita C, Kireev DB, Mason ER, Moerk CT, Nwogbo F, Pearce KH, Richardson TI, Rogers DA, Soni DM, Stashko M, Wang X, Wells C, Willson TM, Frye SV, Young JE, Axtman AD
Alzheimers Dement (N Y). 19.04.2022 8(1):e12253. doi: 10.1002/trc2.12253
PMID: 35434254

2021

Identification of Pyrimidine-Based Lead Compounds for Understudied Kinases Implicated in Driving Neurodegeneration.
Drewry DH, Annor-Gyamfi JK, Wells CI, Pickett JE, Dederer V, Preuss F, Mathea S, Axtman AD
J Med Chem. 01.08.2021 . doi: 10.1021/acs.jmedchem.1c00440
PMID: 34333981

Towards a RIOK2 chemical probe: cellular potency improvement of a selective 2-(acylamino)pyridine series.
Wang CB, Lorente-Macías Á, Wells C, Pickett JE, Picado A, Zuercher WJ, Axtman AD
RSC Med Chem. 01.01.2021 12(1):129-136. doi: 10.1039/d0md00292e
PMID: 34046605

Development of a potent and selective chemical probe for the pleiotropic kinase CK2.
Wells CI, Drewry DH, Pickett JE, Tjaden A, Krämer A, Müller S, Gyenis L, Menyhart D, Litchfield DW, Knapp S, Axtman AD
Cell Chem Biol. 11.01.2021 . doi: 10.1016/j.chembiol.2020.12.013
PMID: 33484635

The Kinase Chemogenomic Set (KCGS): An Open Science Resource for Kinase Vulnerability Identification.
Wells CI, Al-Ali H, Andrews DM, Asquith CRM, Axtman AD, Dikic I, Ebner D, Ettmayer P, Fischer C, Frederiksen M, Futrell RE, Gray NS, Hatch SB, Knapp S, Lücking U, Michaelides M, Mills CE, Müller S, Owen D, Picado A, Saikatendu KS, Schröder M, Stolz A, Tellechea M, Turunen BJ, Vilar S, Wang J, Zuercher WJ, Willson TM, Drewry DH
Int J Mol Sci. 08.01.2021 22(2):. doi: 10.3390/ijms22020566
PMID: 33429995

2020

PKIS deep dive yields a chemical starting point for dark kinases and a cell active BRSK2 inhibitor.
Tamir TY, Drewry DH, Wells C, Major MB, Axtman AD
Sci Rep. 28.09.2020 10(1):15826. doi: 10.1038/s41598-020-72869-9
PMID: 32985588

NeuroChat with Research Assistant Professor Alison Axtman.
Lindsley CW, Axtman AD
ACS Chem Neurosci. 16.09.2020 11(18):2783-2785. doi: 10.1021/acschemneuro.0c00548
PMID: 32933260

SGC-AAK1-1: A Chemical Probe Targeting AAK1 and BMP2K.
Wells C, Couñago RM, Limas JC, Almeida TL, Cook JG, Drewry DH, Elkins JM, Gileadi O, Kapadia NR, Lorente-Macias A, Pickett JE, Riemen A, Ruela-de-Sousa RR, Willson TM, Zhang C, Zuercher WJ, Zutshi R, Axtman AD
ACS Med Chem Lett. 12.03.2020 11(3):340-345. doi: 10.1021/acsmedchemlett.9b00399
PMID: 32184967

2019

CDK16: the pick of the understudied PCTAIRE kinases.
Axtman A, Drewry D, Wells C
Nat Rev Drug Discov. 04.07.2019 18(7):489. doi: 10.1038/d41573-019-00076-x
PMID: 31267068

WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop.
Agajanian MJ, Walker MP, Axtman AD, Ruela-de-Sousa RR, Serafin DS, Rabinowitz AD, Graham DM, Ryan MB, Tamir T, Nakamichi Y, Gammons MV, Bennett JM, Couñago RM, Drewry DH, Elkins JM, Gileadi C, Gileadi O, Godoi PH, Kapadia N, Müller S, Santiago AS, Sorrell FJ, Wells CI, Fedorov O, Willson TM, Zuercher WJ, Major MB
Cell Rep. 02.01.2019 26(1):79-93.e8. doi: 10.1016/j.celrep.2018.12.023
PMID: 30605688

A Chemical Probe Targeting AAK1 and BMP2K
Wells C, Counago R, Limas J, Almeida T, Cook J, Drewry D, Elkins J, Gileadi O, Kapadia N, Lorente-Macías Á, Pickett J, Riemen A, R. Ruela-de-Sousa R, Willson T, Zhang C, Zuercher W, Zutshi R, Axtman A
. 03.09.2019 . doi: 10.26434/chemrxiv.9756785.v1
PMID:

SGC-AAK1-1: A Chemical Probe Targeting AAK1 and BMP2K
Wells C, Couñago RM, Limas JC, Almeida TL, Cook JG, Drewry DH, Elkins JM, Gileadi O, Kapadia NR, Lorente-Macias A, Pickett JE, Riemen A, Ruela-De-Sousa RR, Willson TM, Zhang C, Zuercher WJ, Zutshi R, Axtman AD
ACS Medicinal Chemistry Letters. 29.10.2019 . doi: 10.1021/acsmedchemlett.9b00399
PMID:

2018

Substrate binding allosterically relieves autoinhibition of the pseudokinase TRIB1.
Jamieson SA, Ruan Z, Burgess AE, Curry JR, McMillan HD, Brewster JL, Dunbier AK, Axtman AD, Kannan N, Mace PD
Sci Signal. 25.09.2018 11(549):. doi: 10.1126/scisignal.aau0597
PMID: 30254053

Application of Integrated Drug Screening/Kinome Analysis to Identify Inhibitors of Gemcitabine-Resistant Pancreatic Cancer Cell Growth.
Krulikas LJ, McDonald IM, Lee B, Okumu DO, East MP, Gilbert TSK, Herring LE, Golitz BT, Wells CI, Axtman AD, Zuercher WJ, Willson TM, Kireev D, Yeh JJ, Johnson GL, Baines AT, Graves LM
SLAS Discov. 01.05.2018 2472555218773045. doi: 10.1177/2472555218773045
PMID: 29742358

2017

Progress towards a public chemogenomic set for protein kinases and a call for contributions.
Drewry DH, Wells CI, Andrews DM, Angell R, Al-Ali H, Axtman AD, Capuzzi SJ, Elkins JM, Ettmayer P, Frederiksen M, Gileadi O, Gray N, Hooper A, Knapp S, Laufer S, Luecking U, Michaelides M, Müller S, Muratov E, Denny RA, Saikatendu KS, Treiber DK, Zuercher WJ, Willson TM
PLoS ONE. 03.08.2017 12(8):e0181585. doi: 10.1371/journal.pone.0181585
PMID: 28767711

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